L8 key slides simon
- 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-