Transfer and Metabolism of Prostaglandin E2in the Dual Perfused Human Placenta

Abstract

Prostaglandins (PGs) are potent paracrine hormones that are important for the control of several functions in the uterus and fetus during pregnancy and parturition. PGs are rapidly metabolized to inactive metabolites by prostaglandin dehydrogenase (PGDH). However, the regulation of transfer and metabolism of PGs across the placenta is not well understood. This study used an in vitro dual perfused human placental cotyledon preparation to examine the production of the potent vasoactive and myometrial stimulants PGE2and PGF2α, transfer of PGs from the maternal to the fetal circulation and the metabolism of PGs by PGDH. Secretion of PGE2was greater into the fetal compared to the maternal circulation. PGE2output was higher than PGF2αand concentrations of PGE2and PGF2αmetabolites (PGEM and PGFM) were greater in both fetal and maternal outputs when compared to the primary prostaglandins. Infusion of PGE2into the maternal circulation did not result in increased PGE2efflux but PGEM was output was increased, demonstrating a rapid and efficient metabolism by the placenta. There was no significant transfer of PGE2across to the fetal circulation, although there was some transfer but in the form of inactivated PGEM. There was no significant interconversion of PGE2to PGF2αby the 9-keto-reductase pathway. Expression of PGDH as detected by immunoblot was high in placenta. This PGDH was localized throughout the syncytiotrophoblast at the fetal–maternal interface and also in extravillous trophoblast cells. The presence of PGDH at this site acts to stabilize output of primary PG from the placenta and also as a barrier preventing transfer to the fetal circulation, resulting in the separation of PG homeostasis in the fetus and mother.