(809) The fetal membrane metabolome: arachidonic acid and sex steroid metabolism perturbations associated with preterm rupture

Fetal membranes serve critical immune and mechanical functions in pregnancy, as well as provide signals initiating term and preterm labor. Despite these roles, this feto-maternal interface is often overlooked in reproductive research. Metabolomics has emerged as a powerful tool to understand biochemical footprints of cellular function. We sought to identify differences in the fetal membrane metabolome from cases of preterm premature rupture of membranes (PPROM) compared to term controls.


Study Design:

Untargeted metabolomics was performed on amnion and chorion from cases of PPROM (n=25) and term controls (n=25) matched by race, nulliparity, age, and fetal sex from a prospective pregnancy cohort. Log₂ transformed batch-normalized data were analyzed by two-way ANOVA (p < 0.05) with calculation of false discovery rates (q < 0.1).


Results:

Demographic characteristics were similar between groups (Table 1). Amnion from PPROM had higher abundance of eicosanoid, endocannabinoid, phosphatidylcholine, phosphatidylethanolamine, and fatty acid metabolites compared to term (Table 2). Amnion and chorion from PPROM had lower abundance of sex steroid metabolites, including pregnenolone, progestin, estrogenic, and androgenic metabolites compared to term (Table 2).


Conclusion:

Our study is the first to report a fetal membrane metabolome. We detect evidence of increased metabolism in the arachidonic acid/phospholipid pathway and relative sex steroid deficiency in fetal membranes that rupture preterm. Whether differences in sex steroid metabolites are attributable to PPROM pathophysiology versus advancing gestational age warrants future investigation. Hormonal therapeutics, including local progesterone repletion, may carry potential to mitigate inflammation and fortify membrane integrity, thus reducing preterm birth risk. University of Pennsylvania Research Foundation Award (KG)