embryo transfer newsletter - iets · embryo transfer newsletter september 2010 2 from the president...

Volume 28, Number 3 September 2010

Embryo Transfer NewsletterA Publication of the

International Embryo Transfer Society

Embryo Transfer NewsletterMatthew B. Wheeler, Editore-mail: [email protected]

Vol. 28, No.2 September 2010ISSN 1083-4699

Published quarterly by theInternational Embryo Transfer Society

2441 Village Green PlaceChampaign, IL 61822 USA

(217) 398-4697, FAX: (217) 398-4119E-mail: [email protected]

Web Site: http://www.iets.org

Letters to the Editor are welcomed. Letters must be signed and limited to 300 words and are subject to editing for length, style, and accuracy. Please include name, address, telephone, FAX, and E-mail contact information.

President Letter ............................2

2010 Board of Governors and

Committee Chairs .....................3

Feature Article ..............................4

Election Information ..................12

HASAC Letter ............................17

Invitation to Orlando ..................18

IETS Annual Conference 2011 ..19

2nd DABE Workshop .................21

In this issue

Mammalian oocyte development checkpoints for competence

Trudee Fair

page 4

mailto:[email protected]


http://www.iets.org/2011

Embryo Transfer Newsletter

September 20102

From the PresidentDear Colleagues,

Plans are well underway for the 2011 annual conference to be held in Orlando, Florida. The program co-chairs for our main conference, Eckhard Wolf and Ciro Barros, have de-signed an excellent scientific program with the theme “Re-productive Biotechnology at the Interface Between Animal Agriculture and Biomedical Research.” The meeting should be appealing to all members of our Society. There will be ample opportunity to attend pre- and postconference events and the Practitioners’ Forum and to visit with friends and colleagues. The Preconference Symposium, organized by Cliff Lamb and Jose Santos, will focus on bovine reproduc-tion and embryo technology. The Preconference Workshop on applications of domestic animal stem cells has been ar-ranged by Fulvio Gandolfi. There will also be a Postconfer-ence Workshop arranged by Naida Loskutoff, which will ad-dress important issues associated with transport of gametes, embryos, and other reproductive tissues.Local arrangements for the Orlando meeting are on track with many thanks to Pete Hansen for his efforts. The con-ference will include 339 abstracts and posters presentations

representing 34 different countries. We are grateful for the service efforts of the section editors and the multiple review-ers of abstracts and manuscripts. Please look over the de-tails of the scientific program contained in this newsletter and on the IETS website. Debi Seymour, our secretary, has been busy managing abstracts and manuscript submissions as well as the many preparations needed for the meeting. For this year’s conference we have been able to negotiate a very affordable conference room rate.In 2012 the annual conference of the IETS will be held in Phoenix, Arizona. Pascale Chavatte-Palmer and Rebecca Krisher will be program co-chairs, and Chuck Long will serve as chair of the Local Organization Committee for the meeting. For the 2013 conference, we will be in Hanover, Germany, with Heiner Niemann handling the local arrange-ments and Christine Wrenzycki handling the scientific pro-gram.I look forward to seeing you all in Orlando!

Best Regards,Peter FarinIETS President

Abstract submission details 2001-2011Year Location Submitted Accepted2001 Omaha, USA * 3002002 Foz do Iguacu, Brazil * 4302003 Auckland, New Zealand * 3362004 Portland, USA 379 3442005 Copenhagen, Denmark 377 3392006 Orlando, USA 405 3822007 Kyoto, Japan 442 4232008 Denver, USA 332 3152009 San Diego, USA 331 3162010 Cordoba, Argentina 479 4472011 Orlando, USA 368 339

*Data Not Available


September 20103

President Peter W. Farin, DVM, PhD North Carolina State University College of Veterinary Medicine Raleigh, NC Phone: (919) 513-6469 Fax: (919) 513-6464 E-mail: [email protected]

Immediate Past President Pat Lonergan, PhD University College Dublin Newcastle, County Dublin IRELAND Phone: 353-1-6012147 Fax: 353-1-6288421 E-mail: [email protected]

Vice President Gabriel A Bo, DVM, MVetSc, PhD Instituto de Reproducción Animal Córdoba (IRAC) Córdoba, Argentina Phone: +54-(0)3543-493820 Email: [email protected]

Treasurer Peter J. Hansen, PhD University of Florida Dept of Animal Science Gainesville, FL Phone: (352) 392-5590 Fax: (352) 392-5595 Email: [email protected]

Governors Gregg P. Adams, DVM, MS, PhD, Diplomate ACT University of Saskatchewan Western College of Vet. Medicine Saskatoon, SK CANADA Phone: (306) 966-7411 Fax: (306) 966-7405 Email: [email protected]

Pascale Chavatte-Palmer, DVM, PhD, HDR INRA Jouy En Josas, Yvelines FRANCE Phone: 33 134652558 Fax: 33 134652909 Email: [email protected]

Andras Dinnyes Szent Istvan University Godollo HUNGARY Phone: 36-28-410-200/1642 Fax: 36-28-521-149 Email: [email protected]

T. Lucky Nedambale, PhD Agricultural Research Council (ARC) Irene, Pretoria SOUTH AFRICA Phone: +27-12-672-9378 Fax: +27-12-665-1604 Email: [email protected]

Matthew B. Wheeler, PhD University of Illinois Dept of Animal Sciences Urbana, IL Phone: (217) 333-2239 Fax: (217) 333-8286 Email: [email protected]

2010 IETS Board of Governors

Awards CommitteeRichard Fayrer-HoskenUniversity of GeorgiaAthens, GAUSA

Companion Animal, Non-Domestic and Endangered Species Committee(CANDES)Naida LoskutoffHenry Doorly ZooOmaha, NEUSA

Data Retrieval CommitteeBrad StroudStroud Veterinary Embryo ServiceWeatherford, TXUSA

Domestic Animal Biomedical Embryology (DABE) CommitteeFulvio GandolfiInst. Anatomia of Domestic AnimalsMilano, ITALY

Finance CommitteeGregg P. AdamsUniversity of SaskatchewanSaskatoon, SKCANADA

Health and Safety Advisory CommitteePascale Chavatte-PalmerINRAJouy en Josas, YvelinesFRANCE

Membership CommitteeAndras DinnyesBiotalentum LtdGodollo, HUNGARY

Nominations CommitteePat LonerganUniversity College DublinBelfieldIRELAND

Publications CommitteeMatthew B. WheelerUniversity of IllinoisUrbana, IllinoisUSA

IETS 2010 Committee Chairs











September 20104

CSIRO PUBLISHING

www.publish.csiro.au/journals/rfd Reproduction, Fertility and Development, 2010, 22, 13–20

Mammalian oocyte development: checkpointsfor competence

Trudee Fair

Veterinary Sciences Centre and Lyons Research Farm, School of Agriculture, Food Science andVeterinaryMedicine, University College Dublin, Belfield, Dublin 4, Ireland. Email: [email protected]

Abstract. During the lifespan of the female, biochemical changes occur in the ovarian environment. These changes arebrought about by numerous endogenous and exogenous factors, including husbandry practices, production demands anddisease, and can have a profound effect on ovarian oocyte quality and subsequent embryo development. Despite manyinvestigations, there is no consensus regarding the time or period of follicular oocyte development that is particularlysensitive to insult. Here, the key molecular and morphological events that occur during oocyte and follicle growth arereviewed, with a specific focus on identifying critical checkpoints in oocyte development. The secondary follicle stageappears to be a key phase in follicular oocyte development because major events such as activation of the oocyte transcrip-tome, sequestration of the zona pellucida, establishment of bidirectional communication between the granulosa cells andthe oocyte and cortical granule synthesis occur during this period of development. Several months later, the periovulatoryperiod is also characterised by the occurrence of critical events, including appropriate degradation or polyadenylation ofmRNA transcripts, resumption of meiosis, spindle formation, chromosome alignment and segregation, and so should alsobe considered as a potential checkpoint of oocyte development.

Additional keywords: biomarkers, cattle, follicular oocyte growth, gene expression.

Introduction

Poor reproductive performance in the post partum high-yieldingdairy cow continues to challenge practitioners and scientistsalike. Numerous investigators have endeavoured to identify theprimary causes of low fertility in these animals and the fruitsof their labours have been reviewed extensively (Lucy 2007;Wathes et al. 2007; Diskin and Morris 2008). A complex pictureemerges, implicating milk yield, feed intake, dietary componentsand energy balance as contributors to anoestrus, subtle or silentoestrus behaviour, poor follicle growth, poor-quality oocytes,inadequate corpus luteum function, compromised immune func-tion, uterine infection and an inhospitable uterine environment.A comprehensive review of the interaction of these factors waspublished recently, with particular focus on the impact of both themacro- and micro-environment on follicular oocyte development(Leroy et al. 2008a, 2008b). The authors list several studies thatreport poor oocyte quality and decreased developmental compe-tence (Leroy et al. 2008a). In this regard, the hypothesis that thebiochemical environment in which the follicle grows from theprimordial to ovulatory stage can determine the steroidogeniccapacity of the follicle and the subsequent developmental com-petence of the oocyte in high-yielding dairy cows (Britt 1992) isof particular relevance. The data that have emerged from studiesinvestigating the impact of negative energy balance (NEB) onconception rate are complex with regard to the susceptibility ofthe oocyte to the insult of NEB; it is difficult to identify a partic-ular time point or period of development that is more vulnerableto insult, because studies either span several months post partum

or are further complicated by seasonality. Conception rate (CR)to first service post partum increases as the post partum inter-val becomes longer (Grimard et al. 2006). Although a 50-dayinterval is recommended to allow complete uterine involution,the significantly higher CR observed by Grimard et al. (2006)in high-yielding cows inseminated at ≥90 days after calvingcompared with those inseminated at <70 days could possibly beattributed to differences in the quality of the oocyte presentedfor fertilisation at the two time points. This is supported by thework of Sartori et al. (2002), who reported that Day 5 embryosrecovered from lactating dairy cows 30–90 days after calvingwere of inferior quality or non-viable compared with embryosfrom non-lactating cows or heifers. However, when CRs werecompared following AI or embryo transfer (ET) in animals witha calving to AI or ET interval of 140 days, there was no differ-ence (Sartori et al. 2006). One possible explanation for this isthat the oocytes ovulated in the period up to 90 days after calvingmay be of lower developmental competence.

Reduced fertility has been reported in several mammalianspecies (cattle, sheep, pigs) exposed to heat stress. In a large-scale (>16 500 services) retrospective analysis of lactating dairycows in Queensland, Australia, high heat load was shown tohave a detrimental effect on CR from up to 5 weeks beforeservice (Morton et al. 2007). This delayed effect on oocytequality and embryo development has been reported previously(Roth et al. 2001) and can be overcome by ablation of theimpaired cohorts of follicles for two oestrous cycles or bypassedusing fresh ET (Ambrose et al. 1999; Al-Katanani et al. 2002;

© IETS 2010 10.1071/RD09216 1031-3613/10/010013

Feature Article


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Feature Article14 Reproduction, Fertility and Development T. Fair

Demetrio et al. 2007). When Bos indicus cattle were subjected toa more prolonged, intense period of heat stress, a delayed effecton ovarian follicle dynamics, steroidogenesis and oocyte devel-opmental competence was observed. Furthermore, the carry overeffect was maintained over a period of 105 days, suggesting anegative effect on oocytes at the early stages of follicle devel-opment (Torres-Júnior et al. 2008). Heat stress during in vitromaturation (IVM) has a deleterious effect on the cytoskeleton ofthe oocyte and has been associated with reduced nuclear matura-tion and embryo development, as well as an increased incidenceof apoptosis (Roth and Hansen 2004, 2005). Taken together,these findings suggest that the detrimental effects of prolongedheat stress are manifested as impaired follicle development andreduced or compromised oocyte nuclear maturation.

In order to understand the impact of environmental insults,such as NEB, heat stress, disease or assisted reproduction manip-ulations, on oocyte quality, an understanding of the essentialchanges that occur in the molecular and morphological profilesof the oocyte and its surrounding follicle is imperative. In thepresent review, molecular determinants of mammalian postnataloocyte growth and development will be considered with a view toidentifying critical checkpoints in the oocyte and follicle growthtrajectory that are particularly sensitive to insult.

Follicular oocyte developmentActivation of primordial follicles and preantralfollicle growthMammalian female gametes are stored in the ovaries as inac-tive oocytes surrounded by a single layer of flattened granulosacells (Fair et al. 1997a). Several factors have been identifiedthat appear to act as repressors of follicle activation, includingSohlh2, a critical factor for the maintenance and differentiationof the oocyte during early oogenesis (Choi et al. 2008a), anti mul-lerian hormone (AMH), which possibly acts by attenuating thesensitivity of follicles to FSH (Durlinger et al. 2002), and Pten,which represses the phosphatidylinositol 3-kinase (PI3-K) path-way (Reddy et al. 2008; John et al. 2009). In mice, conventionalknockout or oocyte-specific deletion of these factors results inthe rapid recruitment of primordial follicles to the growing pool,eventually leading to infertility through ovarian follicle depletion(for a review, see Sun et al. 2008).

Primordial follicle activation involves the stimulation ofgranulosa cells to resume mitosis and consequently assume acuboidal shape; within the oocyte cytoplasmic organelles startto proliferate and differentiate (Fair et al. 1997a). In mice, thetranscriptome of the primordial oocyte was shown to be uniqueto that of oocytes obtained from the subsequent stages of fol-licular development (Pan et al. 2005). The authors reported thatthe greatest change in oocyte profile occurred during the primor-dial to primary follicle transition and that this was characterisedby an upregulation in the expression of members of the trans-forming growth factor (TGF)-β superfamily, including Bmp15,Gdf9, Bmp5, Bmp6,Tgfb2 andTgfb3, as well as other growth fac-tors such as Kitld, bFgf and Lif. These factors have stimulatoryaffects on primordial to primary follicle transition, supportingthe long-held theory that the oocyte is the driver of follicle acti-vation (for a review, see Fair 2003). The expression of the genes

involved in primordial follicle activation and subsequent oocytegrowth, granulosa cell proliferation and differentiation appearsto be tightly regulated by several master transcription factors.Microarray analyses of ovaries from knockout mouse modelsof the oocyte-specific transcription factors Figla (Joshi et al.2007), Lhx8 (Choi et al. 2008b) and Foxo3 (Gallardo et al. 2007)have identified many of the genes and pathways under their con-trol. For example, Figla appears to modulate many of the knownmaternal effect genes, including Pou5f1 (Oct 4), Zp1, Zp2, Zp3,members of the Nalp gene family and Dppa3 (Stella; Joshi et al.2007). Interestingly, Pou5f1 expression also appears to be reg-ulated by Lhx8, because global mRNA expression analysis ofLhx8−/− ovaries revealed misexpression of the oocyte-specificgenes Gdf9, Pou5f1 and Nobox and marked downregulation ofKit and Kitl (Choi et al. 2008b). Furthermore, expression of bothNobox and Figla was downregulated in the Lhx8-null ovaries,suggesting that the three transcription factors share commongenetic pathways (Choi et al. 2008b).

These data would suggest that the transition period betweenthe primordial and primary follicle could be an acutely sensitivepoint during oocyte growth. However, it is important to remem-ber that we are extrapolating from studies based on mouse oocytedevelopment and these events occur over a much longer timeframe in cattle. Progression from the primary to the secondaryfollicle stage takes approximately 30 days in cattle (Lussier et al.1987) and is accompanied by key morphological changes, suchas the deposition of zona pellucida material around the oocyteand the synthesis of cortical granules within the oocyte cyto-plasm (Fair et al. 1997a). This stage of development in cattle isalso associated with the onset of nucleolus reorganisation andactivation and the first detection of RNA synthesis (Fair et al.1997b). In the absence of equivalent data, we can only postu-late that this stage in cattle corresponds to the marked changesobserved in the oocyte transcriptome during the primordial toprimary follicle transition in mouse oocytes. It is at this pointin bovine oocyte development that direct communication, inthe form of gap junctions between the surface membranes, isestablished between the oocyte and the surrounding granulosacells. Bidirectional communication between the oocyte and sur-rounding cells facilitates the transfer of amino acids, glucosemetabolites and nucleotides to the growing oocyte (Eppig 1991),which are essential for oocyte and follicle growth and matura-tion. There is evidence that an oocyte–granulosa cell regulatoryloop exists that permits the necessary signalling and metabolicpathways to drive growth and development in both compart-ments (Eppig et al. 2005). Work by Su et al. (2008) using adouble-mutated Gdf9 and Bmp15 mouse model demonstratedthat Gdf9 and Bmp15 are probably major players in this regula-tory loop, with key roles in cumulus cell metabolism, particularlyglycolysis and cholesterol biosynthesis. In cattle and sheep, thesecondary follicle stage is also characterised by the first detectionof Fshr mRNA expression (Tisdall et al. 1995; Xu et al. 1995;Bao and Garverick 1998) and a progressive responsiveness togonadotropins.

In cattle, the transition from the secondary follicle to the ter-tiary follicle takes a further 30 days (Lussier et al. 1987). Thisperiod of oocyte growth is characterised by intensive mRNAand rRNA transcription and an almost quadrupling of oocyte


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Factors reflecting oocyte competence in cattle Reproduction, Fertility and Development 15

volume and further proliferation of the oocyte organelles (for areview, see Fair 2003). Follicular growth is characterised by thecontinued proliferation and differentiation of the cells surround-ing the oocyte to form the theca interna and externa, the basallamina, the cumulus cells and, finally, by the formation of a fluid-filled antral cavity (Driancourt 1991). Locally produced factors,such as insulin-like growth factor (IGF) and members of theTGF-β superfamily, continue to play an important role in bovinepreantral follicle development. This is evidenced by Igfbp2,Igfbp3 and Type 1 Igf receptor mRNA expression in the granu-losa cells of preantral follicles (Armstrong et al. 2003) and thepleiotropic effects of granulosa cell-derived activin, Bmp-2, -5and -6, theca cell-derived Bmp-2, -4 and -7 and oocyte-derivedBmpP-6 in promoting granulosa cell proliferation, follicle sur-vival and prevention of premature luteinisation and/or atresia(Knight and Glister 2006). LHr (Xu et al. 1995), steroidogenicenzymes, P450scc, P450c17 and 3β-HSD mRNA expressionis first detected at the time of formation of the theca interna(for a review, see Webb et al. 2004). Follicles become increas-ingly FSH responsive and their growth and continued survivalbecomes increasingly gonadotropin dependent. The PI3-K/AKTpathway is activated by FSH and is believed to enhance dif-ferentiation and survival of granulosa cells. Indeed, granulosacell-specific disruption of the PI3-K suppressor Pten has beenshown to improve fertility in mice (Fan et al. 2008).

Antral follicle growth, oocyte maturation and ovulationIn cattle, the oocyte and follicle continue to grow in parallel untilthe follicle reaches a diameter of 3 mm; thereafter, the oocytediameter plateaus at approximately 120–130 µm, whereas thefollicle can grow up to 15–20 mm in diameter before ovulation(for a review, see Fair 2003). In total, it takes at least 90 days forthe oocyte to develop from the resting primordial stage up to thepreovulatory stage. During the late stage of the growth phase, theoocyte transcriptome becomes quiescent, the nucleolus restruc-tures to an inactive state and the cytoplasmic organelles migratetowards the oocyte cortex (Fair et al. 1997a). In mice, the relativeabundance of factors associated with transcription decreases dur-ing this period and appears to be a critical factor in the acquisitionof developmental competence (Pan et al. 2005).

In sheep and cattle, antral follicle development is completelygonadotropin dependent and the growing follicles express tran-scripts that encode steroidogenic enzymes, gonadotropin recep-tors and local regulatory factors and their receptors.The selectionof the dominant follicle may be associated with an increased LHresponsiveness. Nutrition can affect the mRNA expression ofcomponents of the ovarian IGF system that regulate the sensitiv-ity of follicles to gonadotropins (Webb et al. 2004). It has beenreported that the dominant follicles of lactating cows are lessoestrogenic than those of non-lactating heifers. Therefore, thesefollicles take longer to grow sufficiently to trigger an increasein LH pulsatility that will stimulate oocyte meiotic maturationand ovulation (Lopez et al. 2004), resulting in prolonged folli-cle dominance, which leads to the ovulation of an aged oocyte(Mihm et al. 1994).

Follicle rupture and the ovulation of a matured oocyte, ini-tiated by the LH surge, is the culmination of several months

of oocyte and follicle growth and follicular cell differentiation,as outlined above. Final oocyte maturation is characterised byseveral key morphological events, including expansion of thesurrounding cumulus cells, disruption of the contact betweenthe corona radiata cells and the oocyte membrane and periv-itelline space formation. In the oocyte cytoplasm, the corticalgranules align just inside the oocyte membrane, the oocytenucleus membrane breaks down releasing the nuclear contentsinto the cytoplasm and the oocyte chromosomes condense, thefirst polar body is extruded and the oocyte arrests at metaphaseof MII (for a review, see Fair 2003). Because oocytes expressfew or no LH receptors, it would appear that, in response toLH, factors such as the epidermal growth factor (EGF)-like fac-tors Areg, Ereg and Btc are released from granulosa cells topromote resumption of meiosis (for a review, see Hsieh et al.2009). Recently, specific granulosa and cumulus cell depletionof extracellular signal-regulated kinase (ERK) 1 and 2 (alsoknown as mitogen-activated protein kinases 1 and 3) was per-formed to investigate their role in ovulation in mice (Fan et al.2009).The Erk1/2 gc−/− females failed to respond to LH: cumu-lus cell expansion, oocyte maturation and ovulation were notinduced. However, the ovaries of these mice contained preovu-latory follicles, indicating that normal follicular development tothe preovulatory stage was not affected. Gene expression pro-filing of granulosa cells from preovulatory follicles identifiedseveral ERK1/2 target genes, such as Cyp19a1 and Sult1e1,which regulate oestradiol biosynthesis and activity, Star andCyp11a1, which are associated with granulosa cell luteinisa-tion, the EGF-like factors Areg, Ereg and Btc and the cumulusexpansion factors Ptgs2, Tnfaip6, Has2, Ptx3 and Pgr. Furtherinvestigations in that study identified the transcription factorCCAAT box enhancer binding protein -beta (C/EBP-β) as adirect target of ERK1/2 and through which the expression ofseveral these genes was mediated.

Meiotic maturation is controlled by three key biochemi-cal pathways: (1) meiotic resumption requires activation ofmaturation-promoting factor (MPF), comprised of a catalyticcyclin-dependent kinase-1 (Cdk1) and a regulatory subunitcyclin B and resulting in germinal vesicle breakdown (GVBD);(2) progression from GVBD through the subsequent stages ofmeiosis is under the control of the anaphase promoting com-plex (APC); and (3) meiotic arrest at MII is under the controlof cytostatic factor (CSF). Regulation of MPF is mostly via theactivity of several kinases and phosphates, whereas APC andCSF are regulated mainly by translational regulation throughsequential waves of polyadenylation and deadenylation (Bellocet al. 2008). Cytoplasmic polyadenylation element binding pro-tein (CPEB), a potential regulator ofAPC, is a sequence-specificRNA-binding protein that regulates polyadenylation-inducedtranslation. It binds several oocyte mRNAs, including Smad1,Smad5, Spindlin, Bub1b, Mos, H1foo, Obox1, Dnmt1o, Tiparp,Trim61 and Gdf9.Ablation of CPEB expression in mouse oocytesresults in abnormal oocyte development, particularly abnormalpolar body formation, a detached cumulus granulosa cell layerand spindle and nuclear anomalies (Racki and Richter 2006).

Global expression profiling of oocytes matured in vivo v.in vitro has identified several biological processes that appearto be particularly sensitive to the maturation environment. For


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16 Reproduction, Fertility and Development T. Fair

example, in rhesus monkey, differentially expressed mRNAswere related to cellular homeostasis, cell–cell interactions, celladhesion, mRNA stability and translation (Lee et al. 2008). Inthat study a relatively small number of transcripts was identi-fied as differentially expressed (n = 59), almost 90% of whichwere upregulated in the IVM oocytes. This finding is quite inter-esting because the in vivo-matured oocytes were primed formaturation using human chorionic gonadotrophin (hCG) and,in mice, equine chorionic gonadotrophin (eCG)-primed oocyteswere shown to have higher developmental competence and amore quiescent transcriptome (De La Fuente and Eppig 2001;Pan et al. 2005). A similar comparison was performed in cattle(Kues et al. 2008); however, the findings of that study differ tothose in mice in that the transcriptome of the in vivo-maturedoocytes was characterised by the detection of expression ofa greater number of genes (12 049 v.11 332 transcripts) andmost (70%) of the genes that were differentially expressed wereupregulated in the in vivo-derived oocytes. The oocytes do notappear to have been primed with eCG in this case. Similarly,transcriptome profiling of IVM MII eggs from a mouse modelof oocyte competence (i.e. oocytes from antral follicles show-ing a chromatin surrounded nucleolus (SN) v. similar stagedoocytes lacking a chromatin ring around the nucleolus (NSN))revealed a higher number of expressed transcripts in compe-tent MII oocytes. However, almost 80% of transcripts that weredifferentially expressed in the two groups were upregulated inthe incompetent MII oocytes (Zuccotti et al. 2008). Further-more, bioinformatic analysis of the upregulated genes foundthat these oocytes preferentially express genes associated withadverse pathways, such as oxidative phosphorylation, mitochon-drial dysfunction and apoptosis. Interestingly, a large number ofthese genes are negatively regulated by the transcription factorPou5f1, which was shown previously to be downregulated inNSN oocytes (Monti et al. 2006).

Insulin concentrations are decreased in high-yielding dairycows during the period of NEB (Beam and Butler 1997). Lowinsulin and glucose levels, together with high levels of growthhormone, stimulate the mobilisation of stored lipids, resulting inhigh concentrations of non-esterified fatty acids (NEFAs) in cir-culating blood plasma, which are also detected in the follicularfluid of dominant follicles. The addition of similar concen-trations of NEFAs to IVM medium resulted in reduced ratesof bovine oocyte meiotic maturation and subsequent fertilisa-tion and blastocyst development (Leroy et al. 2005). Recently,Garnsworthy et al. (2009) reported that the pregnancy rate couldbe improved in post partum cows by feeding a diet to stimu-late higher insulin until cows resumed ovarian cyclic activityafter parturition and then feeding a diet to lower insulin dur-ing the mating period. When the diet to stimulate higher insulinwas continued throughout the treatment up to 120 days postpartum, there was no improvement in pregnancy rate. Thesedata suggest that appropriate intrafolliclular levels of insulinare critical to preantral follicle development, but high levelscan be detrimental at later stages of follicle growth. It is likelythat hyperinsulinaemia directly affects oocyte quality, becauseglobal mRNA expression profiles of matured eggs from polycys-tic ovarian syndrome (PCOS) patients (a condition characterisedby hyperinsulinaemia) were characterised by an upregulation of

several maternal effect genes that regulate oocyte transcriptionand genes associated with chromosome alignment and segrega-tion during meiosis (Wood et al. 2007). Again, these findingssuggest that the appropriate regulation and programming ofthe oocyte transcriptome during the preantral follicular phaseand spindle formation, chromosome alignment and segregationduring the preovulatory phase are particularly critical check-points for oocyte quality that are highly sensitive to the ovarianenvironment.

Oocyte aging

Although oocyte aging is not an issue in dairy cattle husbandrybecause cows are generally replaced after five or six lactations,there is evidence to indicate that bovine oocyte competencedeteriorates with age (Malhi et al. 2007) and perhaps someof the information generated in the following studies may beinformative with regard to oocyte quality in general. Usinga mouse model system, Pan et al. (2008) reported that eggsobtained from old mice (60–70 weeks of age) displayed a sixfoldincrease in the incidence of hyperploidy compared with eggsfrom younger females (6–12 weeks of age). The authors alsoperformed microarray analysis of oocytes and eggs from thesemodels and reported that although only 5% of transcripts weredifferentially expressed in oocytes obtained from the old femalescompared with those from the young females, this fractionincreased to approximately 33% in eggs. The authors suggestedthat the normal pattern of degradation of maternal mRNAs thatoccurs during oocyte maturation is markedly altered in eggsobtained from old mice and could be a contributing factor to thedecline in fertility. In addition, the transcripts that were differen-tially expressed in the aged mice were associated with weakeningof the spindle assembly checkpoint. Breast cancer 1, early onset(BRCA1) may be required for correct spindle formation andchromosomal congression during oocyte meiosis.This transcriptwas less abundant in oocytes from old females and, when reducedusing RNA interference (RNAi) in oocytes obtained from youngfemales, perturbed spindle formation occurred following matu-ration (Pan et al. 2008). In an earlier study, Hamatani et al.(2004) described a 5% difference in transcript expression in eggsobtained from young (5–6-week-old) mice compared with thosecollected from old (42–45-week-old) mice. The difference in theproportion of transcripts differentially expressed in the two stud-ies could possibly be due to the age of the older mice, which wereup to 25 weeks older in the more recent study (Pan et al. 2008).Nevertheless it is of note that Hamatani et al. (2004) reportedthe downregulation of genes involved in mitochondrial function,protection against stress responses and damage, cell survival,oogenesis and gametogenesis in eggs obtained from old femalemice. Consistent with the findings of Pan et al. (2008), tran-scripts related to ‘microtubule cytoskeleton’ and ‘chromosomesegregation’, including Hook1, Tuba1, Tubd1, Dncic2, Kif3b,Rnf19/Dorfin, Pcnt2, Nin and Smc4 L1, were also reported byHamatani et al. (2004) as less abundant in the eggs from theolder mice.

Epigenetics

In mammals, some genes categorised as imprinted genes areexclusively expressed either from maternal or paternal alleles.


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Certain parental origin-specific gene expression is regulated byepigenetic modification of DNA methylation in the differen-tially methylated region (DMR) and, in mice, is coordinatedby the DNA methyltransferase homologue Dnmt3 L (Karetaet al. 2006). Correct expression of imprinted genes is critical forthe proper regulation of embryonic growth and placental func-tion. For example, Dnmt3 L−/− female mice produce matureeggs, but their heterozygous progeny die at mid-gestation due todisrupted expression of maternally imprinted genes, leading toplacental dysfunction (Bourc’his and Proudhon 2008). The initi-ation of imprinted methylation is directly associated with oocytecompetence and is dependent on oocyte size and/or folliculardevelopment. In mice, Dnmt3a, Dnmt3b, Dnmt3 L and Dnmt1otranscript accumulation is initiated once oocytes reach a criticaldiameter of 60–80 µm (Lucifero et al. 2007). Furthermore, theorder of acquisition of methylation among maternally imprintedgenes is believed to occur in accordance with the importance ofthe gene for development; for example, Snrpn, Igf2r and Lit1are methylated early and are crucial to development and growth,whereas Peg1/Mest is late methylating and mutant mice sur-vive (Hiura et al. 2006). The appropriate expression of the DNAmethyltransferase and associated transcripts may be restrictedto the fertile period of the oocyte, because several of these tran-scripts were reportedly downregulated in eggs from older mice(Hamatani et al. 2004).

Because imprinting occurs relatively late in oocyte devel-opment, it appears to be quite susceptible to environmentalchanges and genomic manipulations. Many studies have detailedthe aberrant programming of imprinted genes following cloning(Dean et al. 2003). Most recently, methylation of the DMR of thematernally imprinted gene Snrpn was shown to be decreased inbovine embryos produced by both in vitro culture and somaticcell cloning (Suzuki et al. 2009). The environment in whichoocyte meiotic maturation occurs appears to be particularlycritical for correct epigenetic programming, because data frommouse, human, bovine and rhesus monkey indicate that super-ovulation regimens and IVM compromise or interfere with themaintenance of imprinting in matured eggs and subsequentpreimplantation development (Sato et al. 2007; Fortier et al.2008; Lee et al. 2008; Katz Jaffe et al. 2009; Stouder et al.2009).

Somatic cell markers of competence

Follicular oocyte growth and the acquisition of developmentalcompetence are clearly progressively acquired under the direc-tion of key molecular and biochemical pathways at stage-specifictime points. Thus, the quality of the ovulated egg is not deter-mined by a few key genes, but by the follicular environment inwhich these pathways were orchestrated and the degree to whichappropriate gene expression was challenged along the way. Nev-ertheless, the search for single markers of oocyte competencecontinues and most recent investigations have used microarrayexpression profiling to interrogate follicular cells, cumulus cellsand oocytes from differing models of competence from severalspecies.

In the area of human IVF, the emphasis has been on identify-ing markers of egg quality without sacrificing the egg.Therefore,

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September 20109

Feature Article

18 Reproduction, Fertility and Development T. Fair

follicular cells and cumulus cells have been harvested and retro-spectively profiled using microarray analysis when the outcomeof the IVF treatment is known. Hsd3β1, Fdx1, Cyp19a1, Ser-pine2 and Cdc42 were preferentially expressed in follicular cellsassociated with a clinical pregnancy (Hamel et al. 2008) andthe expression of Bcl2 L11, Pck1 and Nfib in cumulus cellswas significantly correlated with embryo potential and success-ful pregnancy (Assou et al. 2008). Earlier work by McKenzieet al. (2004) used a candidate gene approach and identified thegrowth differentiation factor 9 (GDF9) targets Has2, Ptgs2 andGrem1 as cumulus markers predictive of human oocyte compe-tence based on morphology and embryo development. Severalstudies have reported the expression profiles of cumulus cellsfrom different oocyte competency models in cattle (Assidi et al.2008; van Montfoort et al. 2008; Tesfaye et al. 2009). Dis-appointingly, there was no overlap in the genes identified asparticularly relevant in each study; however, the cumulus expan-sion factor Tnfaip6 was common to the studies of Tesfaye et al.(2009) andAssidi et al. (2008). Furthermore, Inha and Fst, whichwere upregulated in in vivo-matured cumulus cells comparedwith their IVM counterparts (Tesfaye et al. 2009), had previ-ously been associated with higher-competence oocytes whencompared with prepubertal calf oocytes (model of poor oocytecompetence; Patel et al. 2007) and were subsequently shownto play a key role in early bovine embryogenesis (Lee et al.2008). Using the same model, genes encoding the cathepsinfamily of cysteine proteinases (i.e. CTSB, CTSS and CTSZ) wereidentified as markers of poor oocyte quality (Bettegowda et al.2008).

Summary

The activation of the oocyte transcriptome during the early stagesof bovine preantral follicle development appears to be criti-cally important to subsequent oocyte growth and developmentalcompetence, with the appropriate modulation of key transcrip-tion factors, such as Figla, Lhx8 and Pou5f, essential for timelyexpression of oocyte-specific growth factors and glycoproteins.With regard to follicle and oocyte morphology, the sequestra-tion of the zona pellucida creates a protective barrier around theoocyte. The proliferation of the surrounding granulosa cells andthe establishment of bidirectional communication between thegranulosa cells and the oocyte not only provides a means for theexchange of nutrients and the elimination of waste products, butalso selectively filters the products that can come in contact withthe oocyte, whereas cortical granule formation will serve later asa block to polyspermy. During the mid to late antral phase of fol-licle development, perturbations in the animal’s hormonal and/ormetabolic profile appear to impact on the responsiveness of fol-licles to gonadotropins and can lead to altered ovarian dynamics,such as prolonged dominance resulting in a poor-quality agedoocyte. Appropriate degradation or polyadenylation of mRNAtranscripts, spindle formation, chromosome alignment and seg-regation appear to be particularly vulnerable to the maturationenvironment and should also be considered as potential check-points of oocyte development. Potential events and associatedfactors are listed in Table 1.

ReferencesAl-Katanani, Y. M., Paula-Lopes, F. F., and Hansen, P. J. (2002). Effect of

season and exposure to heat stress on oocyte competence in Holsteincows. J. Dairy Sci. 85, 390–396.

Ambrose, J. D., Drost, M., Monson, R. L., Rutledge, J. J., Leibfried-Rutledge,M. L., et al. (1999). Efficacy of timed embryo transfer with fresh andfrozen in vitro produced embryos to increase pregnancy rates in heat-stressed dairy cattle. J. Dairy Sci. 82, 2369–2376.

Armstrong, D. G., Gong, J. G., and Webb, R. (2003). Interactions betweennutrition and ovarian activity in cattle: physiological, cellular andmolecular mechanisms. Reprod. Suppl. 61, 403–414.

Assidi, M., Dufort, I., Ali, A., Hamel, M., Algriany, O., Dielemann, S.,and Sirard, M. A. (2008). Identification of potential markers of oocytecompetence expressed in bovine cumulus cells matured with follicle-stimulating hormone and/or phorbol myristate acetate in vitro. Biol.Reprod. 79, 209–222. doi:10.1095/BIOLREPROD.108.067686

Assou, S., Haouzi, D., Mahmoud, K., Aouacheria, A., Guillemin, Y.,Pantesco, V., Reme, T., Dechaud, H., De Vos, J., and Hamamah, S.(2008). A non-invasive test for assessing profiles of human cumu-lus cells: a proof of concept study. Mol. Hum. Reprod. 14, 711–719.doi:10.1093/MOLEHR/GAN067

Bao, B., and Garverick, H. A. (1998). Expression of steroidogenic enzymeand gonadotropin receptor genes in bovine follicles during ovarianfollicular waves: a review. J. Anim. Sci. 76, 1466–1473.

Beam, S. W., and Butler, W. R. (1997). Energy balance and ovarian fol-licle development prior to first ovulation postpartum in dairy cowsreceiving three levels of dietary fat. Biol. Reprod. 56, 133–142.doi:10.1095/BIOLREPROD56.1.133

Belloc, E., Piqué, M., and Méndez, R. (2008). Sequential waves ofpolyadenylation and deadenylation define a translation circuit that drivesmeiotic progression. Biochem. Soc. Trans. 36, 665–670. doi:10.1042/BST0360665

Bettegowda, A., Patel, O. V., Lee, K. B., Park, K. E., Salem, M., Yao, J.,Ireland, J. J., and Smith, G. W. (2008). Identification of novel bovinecumulus cell molecular markers predictive of ooocyte competence:functional and diagnostic implications. Biol. Reprod. 79, 301–309.doi:10.1095/BIOLREPROD.107.067223

Bourc’his, D., and Proudhon, C. (2008). Sexual dimorphism in parentalimprint ontogeny and contribution to embryonic development. Mol. Cell.Endocrinol. 282, 87–94. doi:10.1016/J.MCE.2007.11.025

Britt, J. H. (1992). Impacts of early postpartum metabolism on folliculardevelopment and fertility. Proc. Annu. Conv. Am. Assoc. Bovine Pract.24, 39–43.

Choi, Y., Yuan, D., and Rajkovic, A. (2008a). Germ cell-specific transcrip-tional regulator sohlh2 is essential for early mouse folliculogenesisand oocyte-specific gene expression. Biol. Reprod. 79, 1176–1182.doi:10.1095/BIOLREPROD.108.071217

Choi, Y., Ballow, D. J., Xin, Y., and Rajkovic, A. (2008b). Lim homeo-box gene, Lhx8, is essential for mouse oocyte differentiation andsurvival. Biol. Reprod. 79, 442–449. doi:10.1095/BIOLREPROD.108.069393

De La Fuente, R., and Eppig, J. J. (2001). Transcriptional activityof the mouse oocyte genome: companion granulosa cells modulatetranscription and chromatin remodeling. Dev. Biol. 229, 224–236.doi:10.1006/DBIO.2000.9947

Dean, W., Santos, F., and Reik, W. (2003). Epigenetic reprogramming inearly mammalian development and following somatic nuclear trans-fer. Semin. Cell Dev. Biol. 14, 93–100. doi:10.1016/S1084-9521(02)00141-6

Demetrio, D. G. B., Santos, R. M., Demetrio, C. G. B., and Vasconcelos,J. L. M. (2007). Factors affecting conception rates following artificialinsemination or embryo transfer in lactating Holstein cows. J. Dairy Sci.90, 5073–5082. doi:10.3168/JDS.2007-0223


September 201010

Feature Article


Diskin, M. G., and Morris, D. G. (2008). Embryonic and early foetal lossesin cattle and other ruminants. Reprod. Domest. Anim. 43, 260–267.doi:10.1111/J.1439-0531.2008.01171.X

Driancourt, M. A. (1991). Follicular dynamics in sheep and cattle. Therio-genology 35, 55–79. doi:10.1016/0093-691X(91)90148-7

Durlinger, A. L., Visser, J. A., and Themmen, A. P. (2002). Regulation ofovarian function: the role of anti-Mullerian hormone. Reproduction 124,601–609. doi:10.1530/REP.0.1240601

Eppig, J. J. (1991). Intercommunication between mammalian oocytes andcompanion somatic cells. Bioessays 13, 569–574.

Eppig, J. J., Pendola, F. L., Wigglesworth, K., and Pendola, J. K. (2005).Mouse oocytes regulate metabolic cooperativity between granulosecells and oocytes: amino acid transport. Biol. Reprod. 73, 351–357.doi:10.1095/BIOLREPROD.105.041798

Fair, T. (2003). Follicular oocyte growth and acquisition of developmen-tal competence. Anim. Reprod. Sci. 78, 203–216. doi:10.1016/S0378-4320(03)00091-5

Fair,T., Hulshof, S. C. J., Hyttel, P., Boland, M., and Greve,T. (1997a). Bovineoocyte ultrastructure in primordial to tertiary follicles. Anat. Embryol.195, 327–336. doi:10.1007/S004290050052

Fair, T., Hulshof, S. C. J., Hyttel, P., Boland, M., and Greve, T.(1997b). Nucleus ultrastructure and transcriptional activity of bovineoocytes in preantral and early antral follicles. Mol. Reprod. Dev.46, 208–215. doi:10.1002/(SICI)1098-2795(199702)46:2<208::AID-MRD11>3.0.CO;2-X

Fan, H. Y., Shimada, M., Liu, Z., Gahill, N., and Richards, J. S. (2008).Targeted disruption of Pten in ovarian granulose cells enhances andextends the life span of luteal cells. Mol. Endocrinol. 22, 2128–2140.doi:10.1210/ME.2008-0095

Fan, H.Y., Liu, Z., Shimada, M., Sterneck, E., Johnson, P. F., Hedrick, S. M.,and Richards, J. S. (2009). MAPK3/1 (ERK1/2) in ovarian granu-losa cells are essential for female fertility. Science 324, 938–941.doi:10.1126/SCIENCE.1171396

Fortier, A. L., Lopes, F. L., Darricarrere, N., Martel, J., and Trasler, J. M.(2008). Suoerovulation alters the expression of imprinted genes inthe midgestation mouse placenta. Hum. Mol. Genet. 17, 1653–1665.doi:10.1093/HMG/DDN055

Gallardo, T. D., John, G. B., Shirley, L., Conteras, C. M., Akbay, E. A.,Haynie, J. M., Ward, S. E., Shidler, M. J., and Castrillon, D. H. (2007).Genomewide discovery and classification of candidate ovarian fertilitygenes in the mouse. Genetics 177, 179–194. doi:10.1534/GENETICS.107.074823

Garnsworthy, P. C., Fouladi-Nashta, A. A., Mann, G. E., Sinclair, K. D.,and Webb, R. (2009). Effect of dietary-induced changes in plasmainsulin concentrations during the early post partum period on pregnancyrate in dairy cows. Reproduction 137, 759–768. doi:10.1530/REP-08-0488

Grimard, B., Freret, S., Chevallier, A., Pinto, A., Ponsart, C., and Humblot, P.(2006). Genetic and environmental factors influencing first service con-ception rate and late embryonic/foetal mortality in low fertility dairyherds. Anim. Reprod. Sci. 91, 31–44. doi:10.1016/J.ANIREPROSCI.2005.03.003

Hamatani,T., Falco, G., Carter, M. G.,Akutsu, H., Stagg, C.A., Sharov,A.A.,Dudekularen, V., and Ko, M. S. H. (2004). Age-associated alterationof gene expression patterns in mouse oocytes. Hum. Mol. Genet. 13,2263–2278. doi:10.1093/HMG/DDH241

Hamel, M., Dufort, I., Robert, C., Gravel, C., Leveille, M. C., Leader,A., andSirard, M.A. (2008). Identification of differentially expressed markers inhuman follicular cells associated with competent oocytes. Hum. Reprod.23, 1118–1127. doi:10.1093/HUMREP/DEN048

Hiura, H., Obata, Y., Komiyama, J., Shirai, M., and Kono, T. (2006). Oocytegrowth-dependent progression of maternal imprinting in mice. GenesCells 11, 353–361. doi:10.1111/J.1365-2443.2006.00943.X

Hsieh, M., Zamah, A. M., and Conti, M. (2009). Epidermal growth factor-like growth factors in the follicular fluid: role in oocyte developmentand maturation. Semin. Reprod. Med. 27, 52–61. doi:10.1055/S-0028-1108010

John, G. B., Shidler, M. J., Besmer, P., and Castrillon, D. H. (2009). Kitsignaling via PI3K promotes ovarian follicle maturation but is dis-pensable for primordial follicle activation. Dev. Biol. 331, 292–299.doi:10.1016/J.YDBIO.2009.05.546

Joshi, S., Davies, H., Porter Sims, L., Levy, S. E., and Dean, J. (2007).Ovarian gene expression in the absence of FIGLA, an oocyte spe-cific transcription factor. BMC Dev. Biol. 7, 67. doi:10.1186/1471-213X-7-67

Kareta, M. S., Botello, Z. M., Ennis, J. J., Chou, C., and Chedin, F.(2006). Reconstitution and mechanism of the stimulation of de novomethylation by human DNMT3L. J. Biol. Chem. 281, 25 893–25 902.doi:10.1074/JBC.M603140200

Katz-Jaffe, M. G., McCallie, B. R., Preis, K. A., Filipovits, J., andGardner, D. K. (2009). Transcriptome analysis of in vivo and in vitromatured bovine MII oocytes. Theriogenology 71, 939–946. doi:10.1016/J.THERIOGENOLOGY.2008.10.024

Knight, P. G., and Glister, C. (2006). TGF-beta superfamily mem-bers and ovarian follicle development. Reproduction 132, 191–206.doi:10.1530/REP.1.01074

Kues, W. A., Sudheer, S., Herrmann, D., Carnwath, W., Havlicek, J. V.,Besenfelder, U., Lehrach, H., Adjayec, J., and Niemann, H. (2008).Genome-wide expression profiling reveals distinct clusters of transcrip-tional regulation during bovine preimplantation development in vivo.Proc. Natl Acad. Sci. USA 105, 19 768–19 773. doi:10.1073/PNAS.0805616105

Lee, Y. S., Latham, K. E., and Vandevoort, C. A. (2008). Effects ofin vitro maturation on gene expression in rhesus monkey oocytes. Phys-iol. Genomics 35, 145–158. doi:10.1152/PHYSIOLGENOMICS.90281.2008

Leroy, J. L. M. R., Vanholder, T., Mateusen, B., Christophe, A., Opsomer, G.,de Kruif, A., Genicot, G., and Van Soom, A. (2005). Non-esterified fattyacids in follicular fluid of dairy cows and their effect on developmen-tal capacity of of bovine oocytes in vitro. Reproduction 130, 485–495.doi:10.1530/REP.1.00735

Leroy, J. L. M. R., Opsomer, G., Van Soom, A., Goovaerts, I. G. F., andBols, P. (2008a). Reduced fertility of in high yielding dairy cows: are theoocyte and embryo in danger? Part I. The importance of negative energybalance and altered corpus luteum function to the reduction of oocyteand embryo quality in high yielding dairy cows. Reprod. Domest. Anim.43, 612–622. doi:10.1111/J.1439-0531.2007.00960.X

Leroy, J. L. M. R.,Van Soom,A., Opsomer, G., Goovaerts, I. G., and Bols, P. E.(2008b). Reduced fertility in high-yielding dairy cows: are the oocyteand embryo in danger? Part II. Mechanisms linking nutrition and reducedoocyte and embryo quality in high-yielding dairy cows. Reprod. Domest.Anim. 43, 623–632. doi:10.1111/J.1439-0531.2007.00961.X

Lopez, H., Satter, L. D., and Wiltbank, M. C. (2004). Relationshipbetween levels of milk production and estrous behavior of lac-tating dairy cows. Anim. Reprod. Sci. 81, 209–223. doi:10.1016/J.ANIREPROSCI.2003.10.009

Lucifero, D., La Salle, S., Bourc’his, D., Martel, J., Bestor, T. H., andTrasler, J. M. (2007). Coordinate regulation of DNA methyltransferaseexpression during oogenesis. BMC Dev. Biol. 7, 36. doi:10.1186/1471-213X-7-36

Lucy, M. C. (2007). Fertility in high-producing dairy cows: reasons fordecline and corrective strategies for sustainable improvement. Soc.Reprod. Fertil. Suppl. 64, 237–254.

Lussier, J. G., Matton, P., and Dufour, J. J. (1987). Growth rates offollicles in the ovary of the cow. J. Reprod. Fertil. 81, 301–307.doi:10.1530/JRF.0.0810301


September 201011

Feature Article20 Reproduction, Fertility and Development T. Fair

Malhi, P. S., Adams, G. P., Mapletoft, R. J., and Singh, J. (2007). Oocytedevelopmental competence in a bovine model of reproductive aging.Reproduction 134, 233–239. doi:10.1530/REP-07-0021

McKenzie, L. J., Pangas, S. A., Carson, S. A., Kovanci, E., Cisneros, P.,Buster, J. E., Amato, P., and Matzuk, M. M. (2004). Human gran-ulose cell gene expression: a predictor of fertilization and embryoselection in women undergoing IVF. Hum. Reprod. 19, 2869–2874.doi:10.1093/HUMREP/DEH535

Mihm, M., Bagusi, A., Boland, M. P., and Roche, J. F. (1994). Asso-ciation between the duration of dominance of the ovulatory follicleand pregnancy rate in beef heifers. J. Reprod. Fertil. 102, 123–130.doi:10.1530/JRF.0.1020123

Monti, M., Garagna, S., Redi, C., and Zuccotti, M. (2006). Gonadotropinsaffect Oct-4 gene expression during mouse oocyte growth. Mol. Reprod.Dev. 73, 685–691. doi:10.1002/MRD.20471

Morton, J. M., Tranter, W. P., Mayer, D. G., and Jonsson, N. N. (2007).Effects of environmental heat on conception rates in lactating dairycows: critical periods of exposure. J. Dairy Sci. 90, 2271–2278.doi:10.3168/JDS.2006-574

Pan, H., O’Brien, M. J., Wigglesworth, K., Eppig, J. J., and Schultz, R. M.(2005). Transcript profiling during mouse oocyte development and theeffect of gonadotrophin priming and development in vitro. Dev. Biol.286, 493–506. doi:10.1016/J.YDBIO.2005.08.023

Pan, H., Pengpeng, M., Zhu, W., and Schultz, R. M. (2008).Age-associated increase in aneuploidy and changes in gene expressionin mouse eggs. Dev. Biol. 316, 397–407. doi:10.1016/J.YDBIO.2008.01.048

Patel, O. V., Bettegowda, A., Ireland, J. J., Coussens, P. M., Lonergan, P., andSmith, G. W. (2007). Functional genomics studies of oocyte competence:evidence that reduced transcript abundance for follistatin is associatedwith poor developmental competence of bovine oocytes. Reproduction133, 95–106. doi:10.1530/REP.1.01123

Racki, W. J., and Richter, J. D. (2006). CPEB controls oocyte growthand follicle development in the mouse. Development 133, 4527–4537.doi:10.1242/DEV.02651

Reddy, P., Liu, L., Adhikari, D., Jagarlamudi, K., Rajeddy, S., et al.(2008). Oocyte-specific deletion of Pten causes premature activationof the primordial follicle pool. Science 319, 611–613. doi:10.1126/SCIENCE.1152257

Roth, Z., and Hansen, P. J. (2004). Involvement of apoptosis in disruptionof developmental competence of bovine oocytes by heat shock duringmaturation. Biol. Reprod. 71, 1898–1906. doi:10.1095/BIOLREPROD.104.031690

Roth, Z., and Hansen, P. J. (2005). Disruption of nuclear matura-tion and rearrangement of cytoskeletal elements in bovine oocytesexposed to heat shock during maturation. Reproduction 129, 235–244.doi:10.1530/REP.1.00394

Roth, Z., Arav, A., Bor, A., Zeronl, R., Braw-Tal, R., and Wolfenson, D.(2001). Effects of environmental heat on conception rates in lactatingdairy cows: critical periods of exposure. Reproduction 122, 737–744.doi:10.1530/REP.0.1220737

Sartori, R., Sartor-Bergfelt, R., Mertens, S. A., Guenther, J. N., Parrish, J. J.,and Wiltbank, M. C. (2002). Fertilization and early embryonic develop-ment in heifers and lactating cows in summer and lactating and dry cowsin winter. J. Dairy Sci. 85, 2803–2812.

Sartori, R., Gümen, A., Guenther, J. N., Souza, A. H., Caraviello, D. Z., andWiltbank, M. C. (2006). Comparison of artificial insemination versusembryo transfer in lactating dairy cows. Theriogenology 65, 1311–1321.doi:10.1016/J.THERIOGENOLOGY.2005.05.055

http://www.publish.csiro.au/journals/rfd

Sato, A., Otsu, E., Negishi, H., Utsunomiya, T., and Arima, T. (2007). Aber-rant DNA methylation of imprinted loci in superovulated oocytes. Hum.Reprod. 22, 26–35. doi:10.1093/HUMREP/DEL316

Stouder, C., Deutsch, S., and Paoloni-Giacobino, A. (2009). Superovu-lation in mice alters the methylation pattern of imprinted genes inthe sperm of the offspring. Reprod. Toxicol., in press. doi:10.1016/J.REPROTOX.2009.06.009

Su, Y. Q., Sugiura, K., Wigglesworth, K., O’Brien, M. J., Affourtit, J. P.,Pangas, S. A., Matzuk, M., and Eppig, J. J. (2008). Oocyte regulationof metabolic cooperativity between mouse cumulus cells and oocytes:BMP15 and GDF9 control cholesterol biosynthesis in cumulus cells.Development 135, 111–121. doi:10.1242/DEV.009068

Sun, Q.Y., Liu, K., and Kikuchi, K. (2008). Oocyte-specific knockout: a novelin vivo approach for studying gene functions during folliculogenesis,oocyte maturation, fertilization, and embryogenesis. Biol. Reprod. 79,1014–1020. doi:10.1095/BIOLREPROD.108.070409

Suzuki, J., Jr, Therrien, J., Filion, F., Lefebvre, R., Goff, A. K., andSmith, L. C. (2009). In vitro culture and somatic cell nuclear transferaffect imprinting of SNRPN gene in pre- and post-implantation stages ofdevelopment in cattle. BMC Dev. Biol. 9, 9. doi:10.1186/1471-213X-9-9

Tesfaye, D., Ghanem, N., Carter, F., Fair, T., Sirard, M. A., Hoelker, M.,Schellander, K., and Lonergan, P. (2009). Gene expression profile ofcumulus cells derived from cumulus–oocyte complexes matured eitherin vivo or in vitro. Reprod. Fertil. Dev. 21, 451–461. doi:10.1071/RD08190

Tisdall, D. J., Watanabe, K., Hudson, N. L., Smith, P., and McNatty, K. P.(1995). FSH receptor gene expression during ovarian follicle devel-opment in sheep. J. Mol. Endocrinol. 15, 273–281. doi:10.1677/JME.0.0150273

Torres-Júnior, J. R. de S., Pires, M. de F. A., de Sa, W. F., Ferreira, A. de M.,Viana, J. H. M., et al. (2008). Effect of maternal heat-stress on folliculargrowth and oocyte competence in Bos indicus cattle. Theriogenology 69,155–166. doi:10.1016/J.THERIOGENOLOGY.2007.06.023

van Montfoort, A. P., Geraedts, J. P., Dumoulin, J. C., Stassen, A. P.,Evers, J. L., and Ayoubi, T. A. (2008). Differential gene expressionin cumulus cells as a prognostic indicator of embryo viability: amicroarray analysis. Mol. Hum. Reprod. 14, 157–168. doi:10.1093/MOLEHR/GAM088

Wathes, D. C., Fenwick, M., Cheng, Z., Bourne, N., Llewellyn, S., Morris,D. G., Kenny, D., Murphy, J., and Fitzpatrick, R. (2007). Influ-ence of negative energy balance on cyclicity and fertility in thehigh producing dairy cow. Theriogenology 68(Suppl. 1), S232–S241.doi:10.1016/J.THERIOGENOLOGY.2007.04.006

Webb, R., Garnsworthy, P. C., Gong, J. G., and Armstrong, D. G. (2004).Control of follicular growth: local interactions and nutritional influences.J. Anim. Sci. 82, 63–74.

Wood, J. R., Dumesic, D. A., Abbott, D. H., and Strauss, J. F. (2007).Molecular abnormalities in oocytes from women with polycystic ovarysyndrome revealed by microarray analysis. J. Clin. Endocrinol. Metab.92, 705–713. doi:10.1210/JC.2006-2123

Xu, Z., Garverick, H. A., Smith, G. W., Smith, M. F., Hamilton, S. A.,and Younquist, R. S. (1995). Expression of follicle stimulating hormoneand luteinizing hormone receptor messenger ribonucleic acids in bovinefollicles during the first follicular wave. Biol. Reprod. 53, 951–957.doi:10.1095/BIOLREPROD53.4.951

Zuccotti, M., Merico, V., Sacchi, L., Bellone, M., Brink, T. C., Bellazzi, R.,Stefanelli, M., Redi, C. A., Garagna, S., and Adjaye, J. (2008). MaternalOct-4 is a potential key regulator of the developmental competence ofmouse oocytes. BMC Dev. Biol. 8, 97. doi:10.1186/1471-213X-8-97


September 201012

Election InformationOnline voting procedure for the Board of Governors elections

As in the last several years, the governor and vice president elections will be done electronically through the IETS website. The voting will be done between the September newsletter (presentation of the candidates and a call to vote) and the De-cember newsletter (presentation of voting results), prior to the annual conference. You can vote only once and only when you have paid your annual fee for the current year. When you go to the IETS website to enter the voting system, you have to enter your last name and ID number, the same as when you access the newsletter. If you cannot remember your ID number, please e-mail Debi Seymour, executive secretary of IETS ([email protected]), to refresh your memory.There are separate pages for new governors and the new vice president. Please vote for two candidates for governor and one candidate for vice president. It is possible to enter other candidates for governor at the end of the page, replacing the option for nominees from the floor in the business meeting. The governors will serve a three-year term starting in January 2011. The vice president will serve a three-year term starting in January 2011, succeeding to president in January 2012 and to im-mediate past president in January 2013.If you do not have access to the Internet, you can fill in the ballot included at the bottom of this document and fax it to Debi Seymour at 217-398-4119.

PLEASE MAKE SURE YOU HAVE VOTED PRIOR TO 15 NOVEMBER, 2010

Retiring GovernorsCompleting their term of service as of January 2011 are Pat Lonergan (Ireland, academic), Andras Dinnyes (Hungary, academic), and Peter Hansen (USA, academic). Remaining on the board as officers will be Peter Farin, immediate past president (USA, academic), and Gabriel Bo, president (Argentina, academic). Remaining on the board as governors for the third year of their terms will be Pascale Chavatte-Palmer (France, academic) and Matt Wheeler (USA, academic). Also remaining on the board as governors for the second year of their terms will be Gregg Adams (Canada, academic) and Lucky Nedambale (USA, industry).

Responsibilities of GovernorsArticle VI, Section 1. The Board of Governors shall be the governing body of the Society, and it shall have control and man-agement of the affairs and business of the Society. Without limiting the generality of the foregoing, the Board of Governors shall approve the format and guidelines for the conduct of the annual conference and business meeting and that for any other meeting or activity including the approval of documents issued in the name of the Society. It shall have the discretion in the disbursement of its funds and may adopt such rules and regulations for the conduct of its business as shall be deemed ap-propriate. The Board of Governors shall report its actions to the Members of the Society at the Annual Meeting as well as in its regularly published newsletter.

Eligibility to Hold OfficeArticle III, Section 3. Only persons holding Regular Membership in the Society and those entitled to the rights of Regular Membership by virtue of their Emeritus status or representing a Sustaining Member are eligible to vote, hold office, or to nominate candidates for office in the Society.Election ProceduresArticle X, Section 1. Election for members of the Board of Governors and for the position of Vice President shall be by mail or electronic ballot, by Regular Members following publication of the names and biosketches of the candidates. Votes shall be counted by the Business Office, which will communicate the results to the Board of Governors. In the event of a tie for the positions of Governor or Vice President, the outcome shall be decided by a ballot among the Board of Governors.

Election InformationArticle VI, Section 2. The Board of Governors shall consist of Governors elected from and by the Regular Membership of the Society by means of an annual ballot. The Governors shall be divided into three classes, each class consisting of two Governors being elected every third year. Each member of a class of Governors shall be elected and hold office for a term of three years and until a successor has been elected and qualified or until such Governor’s early death, resignation or removal


September 201013

in a manner hereinafter provided. In the event that a Governor is serving as Secretary/Treasurer in the third year of his/her term, and designated by the Board in unanimous action to succeed him/herself and if such Governor has committed to serve asSecretary/Treasurer in a succeeding term, such Governor shall not stand for re-election but will continue as a Governor in the class to which such Governor would have been elected. The chairman of the Nominating Committee will include such action in his/her report to the membership. From each annual ballot, a number of Governors equal to that of those whose terms are about to expire, shall be elected for a term of three years. In addition, as deemed necessary by the Board to main-tain the number of Governors, one or more replacement Governors may also be elected by the Regular members when a Governor’s position has become vacant prematurely due to resignation, removal or death. In the event that the elected term of a Governor has expired by the time of commencing his/her term of office as vice president succeeding to president and/or as president succeeding to past president, such officers will continue as members of the Boardof Governors until completion of their terms as past president. Any Governor shall be eligible for re-election but may not serve more than two consecutive three-year terms as a Governor. A Member of the Society who is elected to the position of Vice President and who is not a current Governor shall become ex officio a member of the current Board of Governors. Board members shall take office at the end of the Annual Meeting.

Candidates Put Forward

Vice PresidentHenrik Callesen, DVM, PhD, DVSc (Denmark)

Henrik Callesen is currently research professor at Aarhus University in Denmark. He was born in Denmark in 1956, and from Royal Veterinary and Agricultural University in Co-penhagen, Denmark, he later received his veterinary (1982), PhD (1988), and DrVetSci (1995) degrees. Callesen has worked in basic and applied research in farm animals, start-ing in superovulation, embryo transfer, and ovum pickup in cattle. He later moved into in vitro production and cryopreservation in cattle and pig and also to various methods for monitoring embryo development. His last year’s main efforts have been on somatic cell nuclear transfer to create transgenic pigs as models for human diseases. Callesen gives high priority to close university–industry collaborations and to a strong international network. Other priorities have been lectures to colleagues and students about reproduc-tive technologies and to the public on aspects such as animal welfare and acceptance of controversial technologies. He has been an invited speaker at several meetings nationally

and internationally. Callesen has been an IETS member since 1986, served from 2000 to 2005 on the board as treasurer, and was LOC co-coordinator of the IETS 2005 conference in Copenhagen, Denmark. With his experiences as an IETS member, IETS officer, and organizer of an IETS conference, Henrik Callesen would like again to serve on the IETS board to add to the corporate memory within the board, to continue strengthening the society’s broad scientific coverage from basics to practice and its role in student education, and to recognize the responsibility of the IETS to both animal and society.

Peter J. Hansen, PhD (USA)

Peter J. Hansen is distinguished professor and L. E. “Red” Larson Professor of Animal Sciences at the University of Florida. His research interests center on elucidating ef-fects of elevated temperature on early embryonic development; development of embryo transfer as a reproductive management strategy to overcome infertility in dairy cows; and characterizing interactions between the immune system, the reproductive tract, and the embryo. His education was at the University of Illinois (BS), University of Wisconsin (MS, PhD), University of Florida (postdoc), and University of Guelph (sabbatical). Han-sen has published 220 refereed papers and has received several awards. He is a past presi-dent of the American Society for Reproductive Immunology. He has served the IETS as co-chair of the Scientific Program Committee for the 2001 meeting and chair of the Local Organizing Committee for the 2006 and 2010 meetings, and he currently serves as


September 201014

director and treasurer. If elected, a major goal would be to work with other officers to develop ways for the IETS to influence the setting of research priorities by national and private funding agencies. The embryo is at the center of genetic and assisted reproduction technologies, and the funding to support embryo research is inadequate to fully capture the benefits of these technologies. Other goals would be to continue current IETS efforts to strengthen ties between practitioners and scientists and to continue to support student participation in IETS and assist the new student group (The Morulas).

GovernorPatrick Blondin, PhD (Canada)

Patrick Blondin obtained an MSc in physiology-endocrinology (1993) and a PhD in animal science (1997) at Laval University and then went on to complete a two-year post-doctoral internship at North Carolina State University (1999). He then joined L’Alliance Boviteq as an industrial research fellow to assist in the development of novel ART. Blon-din became director of clinical research in a human ART laboratory to advance the field of reproductive biology in humans. Then, as business developer with McGill University, Blondin helped professors meet key industrial partners to transfer innovative scientific discoveries. Finally, Blondin returned to Boviteq in 2003 as director of research and development. L’Alliance Boviteq is The Semex Alliance’s research subsidiary, where Blondin manages an embryology laboratory that focuses on the development of various biotechnologies such as in vitro fertilization, embryo freezing, and genomics, and a se-men laboratory that focuses on semen quality, semen sexing, sperm fertility, and cryo-

preservation. Blondin collaborates with many scientists from academic, private, and government laboratories and manages services for producers from Canada and the United States to accelerate the genetic gain of their herds or treat infertility problems for elite cows. Furthermore, L’Alliance Boviteq has its own semen sexing laboratory.Blondin is part of the Scientific Program Committee for the next ICAR meeting in Vancouver (2012). He is a member of the Scientific Committee of the Quebec Research Network on Reproduction. Blondin is a member of the Board of Directors for the research network EmbryoGENE and is also a member of the Board of Directors for the CRRA of the University of Montreal. Blondin is associate professor with Université Laval, Université de Montreal, and University of Guelph, codirect-ing many young scientists undergoing graduate studies. A member of IETS since 1995, Blondin now has the opportunity to act as a bridge between scientists and producers to assist in the development and transfer of new, innovative biotechnologies that will address the true needs of many producers in today’s agriculture.

Andras Dinnyes, DVM, PhD, DSc, Prof. Habil. (Hungary)

Andras Dinnyes is a Hungarian veterinarian with PhD and doctor of sciences degrees in animal biotechnology. He has been working in many countries, including the United States (at the Smithsonian Institution as a Fulbright Scholar with Bill Rall on vitrifica-tion, and at the University of Connecticut with Jerry Yang pioneering cattle and rabbit cloning), Belgium with Alban Massip, and Japan with Taku Nagai and the Roslin Insti-tute with Ian Wilmut as team leader for cloning. Currently he is full professor in Hungary and director of his biotech company, BioTalentum Ltd., focusing on animal and human stem cell research. Furthermore, he is invited professor in the Veterinary Faculty of the University of Utrecht, the Netherlands. He has been a member of IETS since 1992, and he was among the funding members of CANDES and DABE. He has been a governor of IETS since 2008, in charge of membership issues, one of the key areas for the future of the society. He has initiated programs to regain lost memberships in regions such as

Europe and Asia and to strengthen the international and US opinion of the leadership position of IETS. After completing his term, he would like to continue his efforts on the board to optimize the benefits for members by promoting active interaction between academia and industry, among various countries and market and research segments of agriculture, medicine, and species preservation. His personal experience on four continents and in academia and industry has prepared him for the diversity of issues to be solved for IETS members.


September 201015

Osamu Dochi, PhD (Japan)

Osamu Dochi received his BSc in agriculture at Rakuno Gakuen Univeristy in Hokkaido, Japan, in 1983, and he received his PhD under the supervision of Dr. Kanagawa at Hok-kaido University, Japan, in 1988. Dochi was employed at the National Livestock Breed-ing Center by the Ministry of Agriculture, Forestry and Fisheries in Japan as a technical official and then research scientist until 1998. In 1998 he joined the faculty of the De-partment of Dairy Science at Rakuno Gakuen University, where he is currently professor of the Laboratory of Applied Reproductive Technologies, teaching animal reproduction and embryo transfer. Dochi has been working in applied research, and his main interests are application of embryo transfer for reproductive management, reproductive physiol-ogy in high-producing dairy cows and genetic improvement, crypreservation of bovine oocytes and embryos, and in vitro fertilization. Dochi attended his first IETS meeting in 1992 in Denver and has attended regularly ever since. He has served as section editor for

abstracts on embryo transfer and organized the Practitioner’s Forum at the IETS annual conference in 2007. He also serves on the data retrieval committee, providing statistics on embryo transfer activity as a representative from Japan. Dochi would like to promote the IETS as an international leader in reproductive technology for livestock improvement and in scientific exchange and collaboration globally for the development of contributing technologies. He would also like to contribute to the participation of young scientists and students in IETS activities.

Daniel Salamone, DVM, PhD (Argentina)

Daniel Salamone was born in Argentina and received his DVM in the College of Veteri-nary Science at the University of Buenos Aires (UBA). He received his MSc at the Uni-versity of Saskatchewan, Canada, and his PhD at the University of Massachusetts, USA. He made a graduated training course in the National Breeding Center, Japan. Since 1985 he has been involved in embryo research. Initially, he worked in disease transmission and embryo transfer in bovine, sheep, and goat. During the period between 1992 and 2000, he worked in IVF, OPU, and oocyte developmental competence in bovine. In 2000 he won the IETS student competition. Since 1997 he has been working in NT, producing several cloned and transgenic bovines in South America between 2001 and 2002 and a cloned horse in 2010. Now he is a professor in the College of Agriculture, UBA, work-ing in micromanipulation and transgenesis in different domestic species such as bovine, horse, sheep, goat, pig, and cat. During 1993, 2007, and 2009, he organized theoretical-

practical courses on IVF, cloning, and transgenesis supported by the Argentinean Brazilian Center of Biotechnology. In addition, he has taught graduate courses at universities in Zaragoza and Valencia, Spain, and has given more than 111 presentations at national and international conferences. He has published more than 25 peer-reviewed papers. He has been an active member of IETS since 1995. Salamone would like to support active participation of a larger number of society members in oral presentations during IETS meetings, preconference and postconference.


September 201016

IETS BALLOT(The use of this ballot is only for those individuals without Internet access.)

Please print and fax this form to Debi Seymour at 217-398-4119.

Nominees for Vice President (Please vote for One) Nominees for Governor (Please vote for Two)___ Henrik Callesen, DVM, PhD, DVSc (Denmark)

___ Peter Hansen, PhD (USA)

___

___

___ Patrick Blondin, PhD (Canada)

___ Andras Dinnyes, DVM, PhD, DSc, Prof. Habil. (Hungary)

___ Osamu Dochi, PhD (Japan)

___ Daniel Salamone, DVM, PhD (Argentina)

___

___

Please note the blank lines are for write-in candidates.

For verification of eligibility to vote, please print and sign your name below:

_______________________________________________ Signature

_____________________________________________ Printed Name


September 201017

As you all know, the IETS has always been a pioneer when it comes to suggesting sanitation regulations of international transport of embryos, semen, and other tissues, and related issues such as biosafety hazards of liquid nitrogen and poten-tial contamination during processing of reproductive tissues. These suggestions are based on scientific research that has been published on these topics. The HASAC Research Sub-committee is listing all of these publications and discussing new evidence that has accrued on these topics on the Friday before the annual meeting of the IETS. Previous chairpersons of this Research Subcommittee include David Stringfellow, who was recently replaced by Dan Givens. Dan had to step down last year because of other duties. He was then replaced by Ann Van Soom, who will chair the next meetings with the help of Michel Thibier and Pascal Chavatte-Palmer, who are also members of this committee. Other members of this subcommittee include Bernard Guérin, Masumi Sato, Tony Wrathall, Andrej Bielanski, Claire Ponsart, Reed Holyoak, Naida Loskutoff , Ann Lindberg (Sw), and Ian Parsonson (Austr.)At the meeting in Cordoba on January 8, 2010, we recorded the new papers published on topics of interest to HASAC. Papers on the risk of contamination of somatic cells collected for the purpose of cloning were especially studied because

for particular viruses of concern, a validated assay needs to be performed. Another topic of concern was the disease cat-egorization of scrapie regarding the risk of transmission via in vivo derived embryos, in which it is essential to distin-guish classical scrapie from atypical scrapie. The HASAC Research Committee agreed that further assessment of the potential for disease transmission resulting from production of embryos from cattle infected with bluetongue virus (BTV) serotype 8 is necessary, and the committee would like to en-courage scientists to investigate this further in full papers.I would like to finish this short report by stressing that em-bryo-pathogen related research is very important from a prac-tical point of view, both for the IETS and for its members. If any members of the IETS or other researchers are interested in this line of research, they can contact the members of the HASAC Subcommittee to discuss potential experimental designs. I would also like to invite anyone who is already involved in embryo-pathogen related research in any species to contact us and apply to become a member of the Research Subcommittee because new members who are attending the IETS meeting each year are very welcome.

Respectfully submitted,Ann Van [email protected]

Letter from the chairperson of the HASAC Research Subcommittee

American Embryo Transfer Association (AETA) & Canadian Embryo Transfer Association (CETA/ACTE)

2010 Joint Scientific Convention

October 21–23, 2010Charlotte-Concord, North Carolina, USA

For information, please visit the AETA website:http://www.aeta.org/2010/

or the CETA/ACTE website:http://www.ceta.ca/convention.htm


http://www.aeta.org/2010/

http://www.ceta.ca/convention.htm


September 201018

Letter of InvitationTo: IETS MembersFrom: Eckhard Wolf and Ciro M. Barros, 2011 Program Co-ChairsSubject: Call for Abstracts

On behalf of the IETS, the chairs of the Local Organizing Committee, and Peter Hansen, we would like to extend a warm invitation to all IETS members to join us at the annual conference of the IETS, scheduled for January 8–12, 2011, in Orlando, Florida, USA.

The theme of the 2011 annual meeting program is

“Reproductive Biotechnology at the Interface BetweenAnimal Agriculture and Biomedical Research”

The program topics include• Follicular Reserve • Growth Factors and Follicular Development• Recent Advances in In Vivo and In Vitro Cryopreservation • Genetic Engineering of Livestock • From Epigenetics to Epigenomics• Molecular Networks as Sensors and Drivers of Fertility

There will also be a Practitioner’s Forum on commercial IVF, and the program will conclude with a keynote address by Dr. Thomas Cremer, titled “Higher order chromatin organization and nuclear architecture in develop-mental biology and cell specialization.”

The Local Organizing Committee is planning a variety of social events. Tours will be available for before and after the meeting. There will be an opening reception on Sunday evening and the closing banquet and activities on Tuesday evening.

Details about the program, including the invited speakers and titles of their presentations, are currently avail-able on the IETS website:


In addition to the main program, there are plans to hold a Preconference Symposium on Saturday (January 8, 2011), “Advances in bovine reproduction and embryo technology,” organized by Dr. Jose Santos and Dr. Cliff Lamb, and an afternoon Preconference Workshop on Saturday (January 8, 2011) titled “Plasticity, fate control, and therapeutic safety of stem cells,” organized by Dr. Fulvio Gandolfi and the DABE committee. All of these events will be held at the Wyndham Orlando Resort in Orlando, Florida. Registration information will be posted on the website as soon as it is available.

We once again urge all members to use the electronic submission format to help keep costs to a minimum.

We sincerely hope that you will all be able to join us in Orlando to participate in IETS 2011!



September 201019

IETS Annual Conference 2011Wyndham Orlando Resort, Orlando, Florida

Program Co-Chairs: Eckhard Wolf and Ciro Barros“Reproductive Biotechnology at the Interface Between Animal Agriculture and Biomedical Research”

Thursday, January 6, 2011

10:00 – 18:00 IETS Board of Governors Meeting

Friday, January 7, 2011

9:00 – 17:00 IETS Board of Governors Meeting

9:00 – 18:00 Health and Safety Advisory Committee (HASAC) – Research Subcommittee 16:00 – 19:00 Registration

Saturday, January 8, 2011

7:00 – 18:00 Registration 8:00 – 17:00 Preconference Symposium – Advances in Bovine Reproduction and Embryo Technology9:00 – 12:00 Heath and Safety Advisory Committee (HASAC) – Regulatory Subcommittee13:00 – 17:00 IETS Foundation Board of Trustees Meeting 13:00 – 18:00 2nd DABE Workshop: Plasticity, Fate Control, and Therapeutic Safety of Stem Cells11:00 – 18:00 Poster Setup11:00 – 18:00 Commercial Exhibit Setup 14:00 – 17:00 Health and Safety Advisory Committee (HASAC) – Food Safety Subcommittee17:00 – 18:00 IETS Student Group (The Morulas) Meet and Greet

Sunday, January 9, 2011

6:30 – 8:00 Poster Setup 7:30 – 8:30 Past President’s Breakfast 7:30 – 8:30 Student Competition Breakfast with Foundation Education Committee 7:00 – 18:00 Registration8:00 – 17:00 Commercial Exhibition 8:30 – 9:30 IETS Foundation Education Committee 8:45 – 9:00 Opening and Welcome (E. Wolf and C. Barros)9:00 – 10:30 Session I: Follicular Reserve9:00 – 9:45 Does Size Matter in Females? James J. Ireland, Michigan State University 9:45 – 10:30 In Vitro and In Vivo Regulation of Follicular Formation and Activation in Cattle

Joanne E. Fortune, Cornell University10:30 – 11:00 Refreshment Break/Exhibition 11:00 – 12:30 IETS Foundation Student Competition Presentations 12:30 – 14:00 Lunch Break 12:30 – 14:00 IETS Board Luncheon with Affiliate Society Representatives 12:30 – 14:00 Health and Safety Advisory Committee (HASAC) - Forms and Certificates Subcommittee 14:00 – 15:30 Session II: Growth Factor and Follicular Development14:00 – 14:45 Recent Insights into Oocyte-Follicle Cell Interactions Provide Opportunities for the Development of New

Approaches to IVM Robert B. Gilchrist, University of Adelaide14:45 – 15:30 Follicular Somatic Cell Factors and Follicle Development José Buratini, Jr., São Paulo State University15:30 – 16:00 Refreshment Break/Exhibition


September 201020

16:00 – 17:30 Session III: Recent Advances in In Vivo and In Vitro Cryopreservation16:00 – 16:45 Cryopreservation and In Vitro Culture of Caprine Preantral Follicles José R. de Figueiredo, LAMOFOPA16:45 – 17:30 Cells Under Pressure: How Sublethal Hydrostatic Pressure – Stress Treatment Increases Gametes’ and

Embryos’ Performance Csaba Pribenszky, Szent Istvan University17:30 – 18:00 Short presentations from submitted abstracts18:00 – 20:00 Health and Safety Advisory Committee (HASAC) Open Meeting20:00 Welcome Reception

Monday, January 10, 2011

7:30 – 16:00 Registration 8:00 – 18:00 Commercial Exhibits 8:00 – 17:00 A/V Library/Speaker Preparation 8:30 – 10:30 Poster Session I/Refreshment Break/Exhibition 10:30 – 11:15 Session IV: Genetic Engineering of Livestock10:30 – 11:15 Perspectives on Transgenic Livestock in Agriculture and Biomedicine – An Update Jorge Piedrahita, North Carolina State University11:15 – 12:30 Session V: From Epigenetics to Epigenomics11:15 – 12:00 Epigenetic Control of Development and Expression of Quantitative Traits Hélène Jammes, INRA, UMR INRA-ENVA 12:00 – 12:30 Short presentations from submitted abstracts12:30 – 14:00 IETS Data Retrieval Committee Meeting 12:30 – 14:00 Lunch Break 12:30 – 13:30 Exhibitors Luncheon with the IETS Board14:00 – 16:00 Session VI: Molecular Networks as Sensors and Drivers of Fertility14:00 – 14:45 Next Generation Sequencing Allows Deeper Analysis and Understanding of Genomes and Transcriptomes

Including Aspects to Fertility Thomas Werner, Genomatix Software Inc.14:45 – 15:30 Dynamic Proteome Signatures in Gametes, Embryos and Their Maternal Environment Georg J. Arnold, Ludwig Maximilian University of Munich 15:30 – 16:00 Short presentations from submitted abstracts16:00 – 16:30 Refreshment Break/Exhibition16:30 – 17:00 IETS Pioneer Award Presentation 17:00 – 18:00 IETS Annual Business Meeting 18:00 – 20:00 Companion Animal, Non-Domestic and Endangered Species (CANDES) Open Meeting 18:00 – 19:00 Domestic Animal Biomedical Embryology Committee (DABE) Open Meeting

Tuesday, January 11, 2011

7:00 – 8:30 Organizational Meeting of the IETS Board of Governors8:00 – 15:00 Registration 8:00 – 13:30 Commercial Exhibits 8:00 – 17:00 A/V Library/Speaker Preparation 8:30 – 10:30 Poster Session II/Refreshment Break/Exhibition 10:30 – 12:30 Practitioners’ Forum: Recent Advances in Superovulation and Embryo Production

Reuben J. Mapletoft, University of Saskatchewan, ChairmanSpeakers: Gabriel A. Bo, Institute of Animal Reproduction Cordoba (IRAC) and University of Villa Maria, Argen-tina: Simplified superovulation protocols using GnRH to control follicular development and one or two injec-tions of FSH for superstimulationPietro S. Baruselli and Manoel Sa Filho, University of São Paulo, Brazil: Use of sexed semen in superovulated Bos indicus donors Richard Remillard, Trans Ova Genetics, USA: Use of sexed semen in superovulated Bos taurus donors and in vitro embryo production

12:30 – 13:30 Lunch Break


September 201021

12:00 – 13:30 Organizational Lunch Meeting of the IETS Foundation 13:30 – 17:00 Commercial Exhibit and Poster Teardown 13:30 – 14:00 IETS Foundation Student Competition Awards, CANDES and HASAC Updates 14:00 – 14:45 IETS Distinguished Service Award Presentation15:00 – 15:45 Session VII: Keynote Address15:00 – 15:45 Nuclear Architecture in Developmental Biology and Cell Specialization Thomas Cremer, Ludwig Maximilian University of Munich15:45 – 16:00 Closing Ceremony 16:30 – 17:30 9th IETS Annual Running Competition19:00 Closing Party

Wednesday, January 12, 2011

7:30 – 11:00 Registration 8:30 – 17:00 Postconference Workshop: International Regulations and Requirements for the Import/Export of Reproductive Bio-

materials: Embryos, Semen, and Tissue Sponsored by the IETS Committee on Companion Animals, Non-Domestic and Endangered Species (CANDES)

Advances in Bovine Reproduction and Embryo TechnologyPreconference Symposium

Orlando, Florida, Wyndham Orlando Resort January 8, 2011

8:00 – 17:00

IntroductionJose Santos, University of Florida; Cliff Lamb, University of FloridaUnderstanding the relationship between the follicle and embryoJo L. Leroy, University of AntwerpMechanism of uterine defense and control of uterine disease in cattleStephen Leblanc, University of GuelphControlling the dominant follicleMilo Wiltbank, University of WisconsinTimed ET programs for management of donor and recipient cowsPietro Baruselli, University of São PauloInfluence of pregesterone on oocyte quality and embryo development in cowsPat Lonergan, University College DublinThe role of cytokines and growth factors to improve pregnancy in IVF-ET programsJeremy Block, University of FloridaDietary manipulations to improve embryonic survival in cattleWilliam Thatcher, University of FloridaWhat technologies are needed in the future of bovine reproduction and ET—RoundtableDon Bennink, North Florida Holsteins; Brad Stroud, Embryo Service; Mel DeJarnette, Select Sires Inc. ConclusionJose Santos, University of Florida; Cliff Lamb, University of Florida


September 201022

2nd DABE Workshop

Plasticity, Fate Control, and Therapeutic Applications of Domestic Animal Stem Cells

Orlando, Florida, Wyndham Orlando Resort January 8, 2011

Welcome and opening remarksFulvio Gandolfi, University of Milano

Production of Oct4/GFP transgenic pigs: A new large animal model for reprogrammingHeiner Niemann, Institut Fuer Tierzucht

Mechanical phenotyping of embryonic stem cellsCarol Keefer, University of Maryland

Development of porcine neural progenitor stem cells for studying and treating Alzheimer’s diseaseVanessa Hall and Poul Hyttel, University of Copenhagen

Equine amniotic-derived stem cells: Progress and perspectivesFausto Cremonesi, University of Milano

The multi-potentiality of skin-derived stem cells in pigsRandall S. Prather and Mingtao Zhao, University of Missouri

Markers of stemness in equine mesenchymal stem cellsAnn Van Soom, Ghent University

Strategies for regeneration of the bone using porcine adult adipose-derived mesenchymal stem cellsMatt Wheeler, University of Illinois

Porcine cardiac progenitor cells: A promising biomedical modelFulvio Gandolfi, University of Milano


September 201023

The goal of this workshop will be to present and discuss the current status of biosafety issues when transporting biomaterials from CANDES as well as humans and livestock for use in biomedical research, embryo production in vivo and in vitro, and artificial insemination. Members of IETS and experts working at regulatory agencies and in relevant research will provide presentations that will cover a variety of topics that will include cloning and stem cell research. The workshop will cover issues such as the potential for disease transmission via reproductive biomaterials and methods to reduce those risks, the cur-rent status of international regulatory agencies in their biosafety guidelines for the import/export of these biomaterials, and suggestions for research or actions to overcome some of the hurdles that currently hamper use of reproductive biomaterials in biomedical and conservation science research. No proceedings articles will be provided; however, the IETS Committee on CANDES will prepare a publication summarizing the results of the workshop in a 2011 issue of the Embryo Transfer Newsletter. The proposed topics and suggested speakers for the program are listed below:

Session I International regulations for the transport of embryos, semen, and tissues from domestic and non-domestic livestock08:00 – 08:45 USDA-APHIS guidelines and regulations regarding the transport of reproductive tissues versus live

animals Dr. Linda Penfold, White Oak Conservation Center, IETS CANDES Subcommittee Co-Chair; and Dr.

William White, USDA-APHIS, Foreign Animal Disease Diagnostic Laboratory08:45 – 09:00 Discussion09:00 – 09:45 OIE and international guidelines and regulations regarding the transport of reproductive tissues versus

live animals Dr. Larry Delver, VM Agriculture Consulting Ltd., Canada, IETS Health and Safety Committee (HASAC)

Regulatory Subcommittee Chair; and Dr. Pascale Chavatte-Palmer, INRA, France, IETS HASAC Chair09:45 – 10:00 Discussion10:00 – 10:30 Break10:30 – 11:15 Biosafety issues and mitigations regarding the use of tissues for cloning Dr. Irinia Polejaeva, Viagen Inc., IETS HASAC member; Dr. Kegin Gregg, Viagen Inc.; and Dr. Duane

C. Kraemer, Texas A & M University, IETS CANDES member11:15 – 11:30 Discussion11:30 – 12:15 Risks and methods for reducing risks of transmitting infectious pathogens when transporting reproduc-

tive biomaterials Dr. Ann Van Soom, Ghent University, IETS HASAC Research Subcommittee Chair; and Dr. Naida Losk-

utoff, Omaha’s Center for Conservation and Research, IETS CANDES Chair12:15 – 12:30 Discussion12:30 – 14:00 Lunch

Session II International guidelines and regulations for the import/export of reproductive tissues from rare or endangered livestock breeds and non-domestic species14:00 – 14:45 Current trends and disease risk assessments for the development of biobanks for tissues from a diverse

array of taxa, including rare domestic and non-domestic livestock Dr. Bill Holt, Zoological Society of London, IETS CANDES Health and Safety Co-Chair14:45 – 15:00 Discussion15:00 – 15:30 CITES international guidelines and regulations regarding the transport of tissues from endangered spe-

cies Dr. Mike Carpenter, US Fish and Wildlife Department, CITES Representative

International Regulations and Requirements for the Import/Export of Reproductive Biomaterials: Embryos, Semen, and Tissues

Sponsored by

The IETS Committee on Companion Animals, Non-Domestic and Endangered Species (CANDES)

Wednesday, January 12, 2011, Windham Orlando Resort, Orlando, Florida


September 201024

15:30 – 16:00 Break16:00 – 17:00 Panel discussion with representatives from USDA-APHIS, IETS HASAC, US Fish and Wildlife Service,

and CITES Moderators: Dr. Gabriela Mastromonaco, Toronto Zoo, Canada, IETS CANDES Technology Subcommittee

Co-Chair; and Dr. Jason Herrick, University of Illinois, IETS CANDES Research Subcommittee

Co-Chair Panel: • Dr. William White, USDA-APHIS, Foreign Animal Disease Diagnostic Laboratory; • Dr. Larry Delver, VM Agriculture Consulting Ltd., Canada, IETS HASAC Regulatory Subcommittee

Chair; • Dr. Pascale Chavatte-Palmer, INRA, France, IETS HASAC Chair; • Dr. Ann Van Soom, Ghent University, IETS HASAC Research Subcommittee Chair; • Dr. Mike Carpenter, US Fish and Wildlife Department, CITES Representative

The focus will be on suggestions as to how to approach regulatory agencies for guidance to standardize regulatory require-ments for reproductive biomaterial transport and for possible methods needed for relaxing certain regulations that currently affect biomedical and conservation research programs—similar to the OIE’s acceptance of the Embryo Appendices in the Animal Health Code based on the efforts of the IETS HASAC.

embryo transfer newsletter - iets · embryo transfer newsletter september 2010 2 from the president...

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