This document discusses assessing the endometrium through non-invasive lipidomic analysis of endometrial fluid secretions. It finds that 1) the lipidomic profile varies across the menstrual cycle and differs in optimal vs suboptimal cycles, 2) lipids are produced by endometrial epithelial cells and may affect blastocysts, and 3) pre-transfer levels of PGE2 and PGF2α in fluid correlate with cycle outcome. The profile of prostaglandin synthases regulating PGE2 and PGF2α differs between receptive and non-receptive endometrium. Prostaglandin receptors are also present on mouse embryos. Overall, the document suggests lipidomic analysis of endometrial secretions

1. 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.

2.  Aspiration of endometrial secretion does not
affect pregnancy rates
Van der Gaast et al. (2002) RBmOnline
Noyes Endometrium vs
Secretion GdA
0 1 2 3 4 5 6
0
20
40
60
80
r2
=0.141 P= 0.049
Histology Endometrial Dating (POD)
SecretionGdA(ng/mgprotein)
 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

3.  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

4. Lipids from EF extracts are identified by liquid chromatography combined
with tandem mass-spectrometry.
MALDI-TOF/TOFLiquid Chromatography ESI-Ion trap
SAMPLE ANALYSIS

5. 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.

6. 0
5
10
15
20
25
30
I II III IV V
mol/g(x10-9)
Group
PGE2
PGF2 alpha
n=51
LIPIDOMIC PROFILE DURING WOI

7. 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(x10-8)
PGE2 PGF2 alpha

8.  Ovulation
 Menstruation
 Myometrium contractility
 Implantation???
LIPID MEDIATORS COORDINATE DIFFERENT
EVENTS
PGH2 PGD2
PGF2a 11b-PGF2aPGE2
AKR1C3
bimatoprost
CBR1
CAY10607
cPGES
mPGES1
MK886
DRB
Membrane Phospholipids
Arachidonic acid
cPLA2
COX
AKR1B1
AKR1C1
1-phenyl-1-cyclopentane carboxylic acid
mPGES2

9. 0
0,5
1
1,5
2
2,5
cPGES mPGES1 mPGES2 AKR1C3 AKR1C1 CBR1
Relativeunits/GAPDH
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.

10. HUMAN PGs RECEPTORS ON MOUSE EMBRYOS
Antibody DAPIAntibody DAPI
EP1
EP2
EP3
EP4
FP
C-