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P.J. HansenDept. of Animal Sciences, University of Florida
Importance of Immune Function for Optimal Reproduction of Dairy Cows
Laval
Daugh
ter Pr
egnanc
y Rate
2426283032343638
Year2004 2006 2008 2010 2012 2014 2016
Milk y
ield (lb
)
2600026500270002750028000
RECENT CHANGES IN FERTILITY AND MILK YIELD IN US HOLSTEINS
• Genetic selection• Timed AI
The Next Major Increase in Fertility Will Occur by Enhancing Dairy Cow Health
Sick cow Healthy cowInfertile cow Fertile cow
MAIN POINT 1 HEALTHY COWS ARE FERTILE COWS
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Sick cow Healthy cow
Immune-compromised cow Immunocompetent cow
Infertile cow Fertile cow
MAIN POINT 2 – COWS ARE OFTEN SICK BECAUSE THEY HAVEPOOR IMMUNE FUNCTION
Sick cow Healthy cow
Immune-compromised cow Immunocompetent cow
Infertile cow Fertile cow
MAIN POINT 3: IMPROVING IMMUNE FUNCTION SHOULD INCREASE FERTILITY
improved immune function
Sick cow Healthy cowInfertile cow Fertile cow
MAIN POINT 1 HEALTHY COWS ARE FERTILE COWS
ImagesDenise RichLavalwww.heidihanskoch.comresumption of cyclicity
Establishment of pregnancy
Survival to term
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Category Cyclic, % Adjusted OR (95% CI) PHealthy 84.1 1.00 ---1 case of disease 80.0 0.97 (0.72 – 1.30) 0.83> 1 case of disease 70.7 0.60 (0.44 – 0.82) 0.001
Type of health problemCalving problem 70.5 0.52 (0.40 – 0.68) < 0.001Metritis 63.8 0.37 (0.28 – 0.50) < 0.001Clinical endometritis 68.9 0.51 (0.37 – 0.71) < 0.001Fever postpartum 80.0 0.55 (0.40 – 0.74) < 0.001Mastitis 81.5 0.87 (0.55 – 1.36) 0.53Clinical ketosis 77.7 0.71 (0.47 – 1.07 0.10Lameness 85.0 0.82 (0.52 – 1.30) 0.40Pneumonia 88.9 1.78 (0.22 – 14.34) 0.59Digestive problem 60.7 0.54 (0.25 – 1.17) 0.12
5,719 postpartum dairy cows evaluated daily for health disorders in seven dairy farms in the US.
Health Problems in the First 60 DIM and Resumption of Estrous Cyclicity in Dairy Cows
Santos et al. (2010) Reprod. Dom. Rum. VII:387-404
Category Pregnant, % Adjusted OR (95% CI) P
Healthy 51.4 1.001 case of disease 43.3 0.79 (0.69 – 0.91) 0.001> 1 case of disease 34.7 0.57 (0.48 – 0.69) < 0.001
Type of health problemCalving problem 40.3 0.75 (0.63 – 0.88) < 0.001Metritis 37.8 0.66 (0.56 – 0.78) < 0.001Clinical endometritis 38.7 0.62 (0.52 – 0.74) < 0.001Fever postpartum 39.8 0.60 (0.48 – 0.65) < 0.001Mastitis 39.4 0.84 (0.64 – 1.10) 0.20Clinical ketosis 28.8 0.50 (0.36 – 0.68) < 0.001Lameness 33.3 0.57 (0.41 – 0.78) < 0.001Pneumonia 32.4 0.63 (0.32 – 1.27) 0.20Digestive problem 36.7 0.78 (0.46 – 1.34) 0.38
5,719 postpartum dairy cows evaluated daily for health disorders in seven dairy farms in the US
Health Problems in the First 60 DIM and Pregnancy in Dairy Cows
Category Loss, % Adjusted OR (95% CI) PHealthy 8.9 1.00 ---1 case of disease 13.9 1.73 (1.25 – 2.39) < 0.001> 1 case of disease 15.8 2.08 (1.36 – 3.17) < 0.001
Type of health problemCalving problem 15.9 1.67 (1.16 – 2.40) < 0.01Metritis 11.3 1.01 (0.71 – 1.60) 0.76Clinical endometritis 15.1 1.55 (1.04 – 2.32) 0.03Fever postpartum 18.0 2.00 (1.24 – 3.14) < 0.01Mastitis 19.8 2.62 (1.48 – 4.64) < 0.001Clinical ketosis 14.6 1.64 (0.75 – 3.59) 0.22Lameness 26.4 2.67 (1.38 – 5.12) < 0.01Pneumonia 16.7 1.87 (0.40 – 8.69) 0.42Digestive problem 15.8 1.81 (0.52 – 6.32) 0.35
Health Problems and Pregnancy Loss in the First 60 d of Gestation in Dairy Cows
5,719 postpartum dairy cows evaluated daily for health disorders in seven dairy farms in the US.Santos et al. (2010) Reprod. Dom. Rum. VII:387-404
Health status Value Adjusted odds ratio
P% cyclic at day 49 postpartumNo disease 91.1 1.00 --1 clinical disease 88.3 0.74 0.22> 1 clinical disease 77.8 0.34 <0.01% pregnant at first AINo disease 66.9 1.00 --1 clinical disease 56.5 0.64 <0.01> 1 clinical disease 40.8 0.34 <0.01% pregnancy loss, day 30 and 65No disease 9.2 1.00 --1 clinical disease 12.3 1.38 0.34> 1 clinical disease 26.7 3.58 <0.01
Association of disease with postpartum reproduction in 957 cows on two dairies in Florida (Ribeiro et al. J Dairy Sci. 96:5682, 2013)
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Ribeiro et al., J Dairy Sci 99:2201 (2016)
It is Not Only Uterine Disease That Causes InfertilityResults from 5085 cows bred by AI or ET
ImagesDenise RichLavalwww.heidihanskoch.comresumption of cyclicity
Establishment of pregnancy
Survival to term
Body temperature
Cytokines and otherimmune and inflammatoryproducts
Uterine infectious disease
Bacterial toxins
Energy balance
IMMUNE & INFLAMMATORY
SYSTEMSINFECTIOUS AGENTS
energy consumption feed intake metabolism
Hypothalamic-pituitary axis
Ovary
Bacterial toxins
Cytokines & inflammatory products
TISSUE DAMAGE
Sick cow Healthy cow
Immune-compromised cow Immunocompetent cow
Infertile cow Fertile cow
MAIN POINT 2 – COWS ARE OFTEN SICK BECAUSE THEY HAVEPOOR IMMUNE FUNCTION
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Bullvine
INSULT TO HEALTH(injury, inflammation, bacteria, virus)
Resolves insult Does not resolve
--------Immune system------
Sheldon et al., Biol. Reprod. 81:1025 (2009)
Incidence of Uterine Infections and Disease During the Postpartum Period in Cattle
Cows prone to metritis and endometritis experience poor neutrophil function before calving
Hammon et al., Vet ImmunolImmunopathol 113:21 (2006)
endometritis
No uterine disease
metritis
Cytoch
rome c
reduct
ionMy
elopero
xidase a
ctivity
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CON DES implant Days PP
C% (n)
M% (n)
P% (n)
C% (n)
M% (n)
P% (n)
16 33 (3) 33 (3) 33 (3) 16 70 (7) 0 30 (3)23 56 (5) 11 (1) 30 (3) 23 80 (8) 20 (2) 030 60 (6) 10 (1) 20 (2) 30 70 (7) 30 (3) 037 50 (5) 40 (4) 0 37 90 (9) 10 (1) 0Overall 50 (19) 24 (9) 21 (8) 78 (31) 15 (6) 7.5 (3)
Frequencies of cervical discharge scores during the postpartum period for CON and DESL implant groups (Silvestre and Thatcher)
OR=3.2Imp1, CI=0.80 – 12.82; P=0.09Implant added 1-4 days postpartum C = Clean; M = mucupurulent; P = purulent
n=699
Immunize type 1 and 2 test Ag wk -8,-3, 0 rel to calving
Measure Ab titerswk -8,-3,0 and +2 rel to calving
Antibody-mediated immune response(AMIR)Cell-mediated immune response(CMIR)
Skin hypersensitivity test to type 1 Agwk +1 rel to calving DiseaseincidenceIR=Average of AMIR + CMIRCalculated EBV for immune responses using pedigree information
Incidence of Disease (%) as affected byEBV for Overall Immune Response (IR)Disease Low EBV for
IR (n=153)Average EBV for IR (n=407)
High EBV for IR (n=139)
Mastitis 25.7ab 29.0a 19.4bMetritis 7.2 4.7 4.3Ketosis 5.9 5.7 5.8Displaced abomasum
5.8a 1.7b 3.6ab
Retained fetal membranes
13.1a 5.9b 5.0b
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Thompson-Crispi et al., Clin. Vaccine Immunol 20:106 (2013)
Incidence Rate of Clinical Mastitis for Cows Classified by EBV for Antibody-Mediated Immune Responses (cases/100 cow-years)
Administration of Pegylated G-CSF Increases Neutrophil Number and Reduces Incidence of Clinical Mastitis
Canning et al., J Dairy Sci 100:6504 (2017)
~7 d before and 24 h after calving
Bred heifers: 4 g/45 kg BW as daily top-dress 60 d before calving (n=20) or grain mix control (n=20)
A proprietary product that modulates the immune response to a pathogen challenge, especially during periods of immune suppression or dysfunction.
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Effects of OmniGen-AF on Incidence of Adverse Health Effects
Nace et al., Vet Immunol Immunopathol 161:240 (2014)
Effects of OmniGen-AF on Mammary Infection, SCC and Milk Yield
Sick cow Healthy cow
Immune-compromised cow Immunocompetent cow
Infertile cow Fertile cow
MAIN POINT 2 – COWS ARE OFTEN SICK BECAUSE THEY HAVEPOOR IMMUNE FUNCTION
• Cows that get metritis have lower PMN function• Progesterone is immunosuppressive; concentrations are related to incidence of uterine disease• Cows with genetic merit for low immune response are less likely to develop disease• Boosting immune function decreases incidence of specific disease
Sick cow Healthy cow
Immune-compromised cow Immunocompetent cow
Infertile cow Fertile cow
MAIN POINT 3: IMPROVING IMMUNE FUNCTION SHOULD INCREASE FERTILITY
improved immune function
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Neutrophils (green) phagocytosing E. coli (red) injecteds.c. into zebrafish larvaeColucci-Guyon et al., J Cell Sci 2011; 124:3053
Strategies to Enhance Immune Function in Postpartum Dairy Cows• Regulation of calcium metabolism to reduce hypocalcemia• Improving energy balance• Administer nonsteroidal anti-inflammatory molecules• Feed nutritional supplements that enhance immune function (OmniGen-AF)• Administer biologicals that regulate immune function (Imrestor)• Select for cows with superior genetics for immune function
Administration of G-CSF Increases Neutrophil Numberand Reduces Incidence of Clinical Mastitis
Canning et al., J Dairy Sci 100:6504 (2017)
~7 d before and 24 h after calving
Canning et al., J Dairy Sci 100:6504 (2017)
Saline G-CSFMetritis 3.0% (9/300) 4.8% (14/290)Failure to be detected in estrus, day 80
9.4% (27/286) 4.6% (13/285)*Failure to conceive at first service
61.8% (160/259) 57.4% (156/272)
Incidence of Reproductive Problems as Affected by Pegylated G-CSF
10,238 primiparous and multiparous Holsteins from 17 dairies in MexicoTreatment with Imrestor® (i.e, pegbovigrastrim; i.e., pegylated G-CSF) at~ day 7 before calving and at 24 h after calving
Untreated G-CSFIncidence of clinical mastitis (%) 4.9 3.7**Incidence of retained placenta (%) 5.8 5.6Incidence of metritis (%) 8.4 9.8*
G-CSF treated cows had 5.8% greater chance of being inseminated by day 100 PP(Cox-Hazard ratio=1.058; P<0.05)
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ImagesDenise RichLavalwww.heidihanskoch.comresumption of cyclicity
Establishment of pregnancy
Survival to term
Manage transition nutrition toavoid excessive NEB, hypocalcemia
Consider treatmentsthat boost immunity
Possibly prevent negative effectsof overactivation of immune function – chronic inflammationSelect for genes controlling immune function
Pete Hansen [email protected]