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-