Lipidomic profiling of endometrial fluid as a non-invasive diagnostic tool of human endometrial receptivity

Abstract

OBJECTIVE: To investigate the lipid content in human endometrial fluid and the molecular mechanisms of endometrial prostaglandin (PG) production, in order to develop a non-invasive diagnostic tool of endometrial receptivity. DESIGN: Open blinded study on healthy female donors. MATERIALS AND METHODS: Endometrial fluid samples were collected from 39 fertile, regularly cycling volunteers aged 19-36 years with a normal BMI. Lipids content was identified by liquid chromatography combined with tandem mass-spectrometry. PG production was investigated using qPCR and immunohistochemistry in endometrial tissue. RESULTS: Lipids profile in endometrial fluid samples was analyzed in group I (days 0-8, n=8), group II (days 9-14, n=8), group III (days 15-18, n=8), group IV (days 19-23, n=8) and group V (days 24-30, n=7). Interestingly, during the clinical window of implantation (Group IV) PGE2 and PGF2α levels were significantly increased compared to all other groups. Analyses of endometrial epithelium at the mRNA and protein level point at mPGES1 and AKR1C3 as the enzymes responsible for the production of PGE2 and PGF2α, respectively, during the periimplantation period. We did not detect significant changes in the levels of CBR1 and AKR1C1, suggesting that production of PGE2 and PGF2α is mainly the result of PGH2 metabolism rather than an enzyme-driven switch between them.Tabled 1PGE2 and PGF2α concentration in human endometrial fluidPGE2 (moles/g ± SD)PGF2α (moles/g ± SD)Group I1.3E-09 ± 1.5E-092.9E-09 ± 2.9E-09Group II9.2E-11 ± 1.4E-101.1E-10 ± 1.4E-10Group III2.6E-09 ± 4.1E-094.5E-09 ± 5.4E-09Group IV∗U-Mann Whitney p<0.01 between group IV and all other groups.6.7E-09 ± 5.7E-092.4E-08 ± 1.9E-08Group V1.6E-09 ± 2.5E-093.5E-09 ± 4.1E-09∗ U-Mann Whitney p<0.01 between group IV and all other groups. Open table in a new tab CONCLUSION: PGE2 and PGF2α may represent novel predictors of human endometrial receptivity, thus opening the possibility for a non-invasive method to determine the clinical window of implantation.