title: Transfer and metabolism of prostaglandin E(2)in 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 PGE(2)and PGF(2alpha), transfer of PGs from the maternal to the fetal circulation and the metabolism of PGs by PGDH. Secretion of PGE(2)was greater into the fetal compared to the maternal circulation. PGE(2)output was higher than PGF(2alpha)and concentrations of PGE(2)and PGF(2alpha)metabolites (PGEM and PGFM) were greater in both fetal and maternal outputs when compared to the primary prostaglandins. Infusion of PGE(2)into the maternal circulation did not result in increased PGE(2)efflux but PGEM was output was increased, demonstrating a rapid and efficient metabolism by the placenta. There was no significant transfer of PGE(2)across to the fetal circulation, although there was some transfer but in the form of inactivated PGEM. There was no significant interconversion of PGE(2)to PGF(2alpha)by 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.
authors.affiliation: Department of Obstetrics and Gynaecology, Western General Hospital University of Edinburgh, Edinburgh, UK.
authors.forename: A P
authors.initials: AP
authors.lastname: Greystoke
authors.forename: R W
authors.initials: RW
authors.lastname: Kelly
authors.forename: R
authors.initials: R
authors.lastname: Benediktsson
authors.forename: S C
authors.initials: SC
authors.lastname: Riley
mesh_terms: D001693:Biological Transport, Active; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange; D010477:Perfusion; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
chemical_list: D015237:Dinoprost; D006911:Hydroxyprostaglandin Dehydrogenases; D015232:Dinoprostone