Lead exposure at the feto-maternal interface: a cause for concern for fetal membrane trophoblasts.

The integrity of fetal membranes enables biological functions that protect the fetus and maintain the pregnancy. Any compromise in fetal membrane function can predispose a pregnant woman to prelabor rupture of the membranes (pPROMs) and subsequently to preterm birth (PTB). Epidemiologic data suggest that lead exposure during pregnancy is one of several risk factors associated with PTB and pPROM. This heavy metal can cross placental and fetal membrane barriers, disrupting homeostasis in these tissues. Autophagy contributes to the maintenance of fetal membrane homeostasis during gestation, and dysfunctional autophagy is associated with pPROM. In this study, we determined the mechanistic impact of lead-induced cellular changes, autophagy, senescence, and inflammation in chorion trophoblast cells (CTCs) and amnion epithelial cells (AECs) of the fetal membranes. Lead exposure in CTCs induced autophagy dysfunction (increase in LC3B-II), augmented senescence (increased SA-β-galactosidase activity), and increased the release of inflammation. In AECs, lead exposure did effect autophagy, senescence, nor inflammation. The differential changes observed in CTCs and AECs after exposure to high lead concentrations may promote the weakening of fetal membranes and contribute to preterm rupture.