l8 key slides simon (1)
TRANSCRIPT
Non invasive technologies to assess the most receptive endometrium: LIPIDOMICS
Prof. Carlos Simón MD, PhD
Professor Obs/Gyn, University of Valencia. Scientific Director, Fundación IVI.
Aspiration of endometrial secretion does not affect pregnancy rates
Van der Gaast et al. (2002) RBmOnline
Noyes Endometrium vsSecretion GdA
0 1 2 3 4 5 60
20
40
60
80r
2=0.141 P= 0.049
Histology Endometrial Dating (POD)
Se
cre
tio
n G
dA
(n
g/m
g p
rote
in)
Glycodelin levels correlate with menstrual cycle phase on endometrial aspirations
Van der Gaast et al. (2009) BJOG
The profile of cytokines can be determined in endometrial secretions Simón et al. (1996) J Reprod Immunol
Boomsma et al. (2009) RBmOnline
SECRETOMICS OF ENDOMETRIAL FLUID (EF): NON-INVASIVE DIAGNOSIS
The lipidomics can be defined as large-scale study of lipid species present in a cell or biological system and their interacting pathways and metabolic networks.
LIPIDOMICS
Lipids from EF extracts are identified by liquid chromatography combined with tandem mass-spectrometry.
MALDI-TOF/TOF Liquid Chromatography ESI-Ion trap
SAMPLE ANALYSIS
OBJECTIVES
a) To demonstrate the specificity of the lipidomic profile in endometrial secretions in optimal, suboptimal and refractory endometrial cycles.
b) To understand the production mechanism/s of these lipids by human endometrial epithelial cells and their putative effects in blastocysts.
c) To prove the diagnostic accuracy of PGE2, PGF2 levels in EF
obtained 24 hours before embryo transfer by correlating them with cycle outcome.
0
5
10
15
20
25
30
I II III IV V
mo
l/g
(x1
0-9
)
Group
PGE2
PGF2 alpha
n=51
LIPIDOMIC PROFILE DURING WOI
Comparison between HRT without vs with IUD in the same patient in the next cycle
HRT (n=25) HRT and IUD (n=25)
0
1
2
3
4
5
6
P0
(n=5)
P0+DIU
(n=5)
P1
(n=5)
P1+DIU
(n=5)
P3
(n=5)
P3+DIU
(n=5)
P5
(n=5)
P5+DIU
(n=5)
P7
(n=5)
P7+DIU
(n=5)
mol
/g (x
10-8
)
PGE2 PGF2 alpha
Ovulation
Menstruation
Myometrium contractility
Implantation???
LIPID MEDIATORS COORDINATE DIFFERENT EVENTS
PGH2 PGD2
PGF2a 11b-PGF2a PGE2
AKR1C3
bimatoprost
CBR1
CAY10607
cPGES
mPGES1
MK886
DRB
Membrane Phospholipids
Arachidonic acid
cPLA2
COX
AKR1B1
AKR1C1
1-phenyl-1-cyclopentane carboxylic acid
mPGES2
0
0,5
1
1,5
2
2,5
cPGES mPGES1 mPGES2 AKR1C3 AKR1C1 CBR1
Rela
tive
un
its/G
AP
DH
P0
P5
*
*
*
1 2 3 1 2 3
+P day0 +P day5
cPGES
mPGES2
AKR1C3
AKR1C1
CBR1
GAPDH
mPGES1
23 KDa
15 KDa
33 KDa
36 KDa
37 KDa
30 KDa
REGULATION OF PG SINTHASES IN HUMAN ENDOMETRIUM
PGE2 and PGF2 are regulated by PG synthases in R vs non-R endometrium.
HUMAN PGs RECEPTORS ON MOUSE EMBRYOS
Antibody DAPI Antibody DAPI
EP1
EP2
EP3
EP4
FP
C-