Greystoke A P, Kelly R W, Benediktsson R, Riley S C
Department of Obstetrics and Gynaecology, Western General Hospital University of Edinburgh, Edinburgh, UK.
Placenta. 2000 Jan;21(1):109-14. doi: 10.1053/plac.1999.0452.
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.
前列腺素（PGs）是强效的旁分泌激素，对孕期和分娩期间子宫及胎儿的多种功能控制至关重要。PGs可被前列腺素脱氢酶（PGDH）迅速代谢为无活性的代谢产物。然而，PGs跨胎盘转运和代谢的调控机制尚不清楚。本研究采用体外双灌注人胎盘小叶制备方法，检测强效血管活性物质和子宫肌层刺激物前列腺素E2（PGE2）和前列腺素F2α（PGF2α）的产生、PGs从母体循环向胎儿循环的转运以及PGDH对PGs的代谢情况。与母体循环相比，PGE2向胎儿循环的分泌量更大。PGE2的输出量高于PGF2α，与主要前列腺素相比，胎儿和母体输出中PGE2和PGF2α代谢产物（PGEM和PGFM）的浓度更高。向母体循环中输注PGE2并未导致PGE2流出增加，但PGEM输出增加，表明胎盘具有快速有效的代谢作用。虽然有一些PGE2以无活性的PGEM形式转运至胎儿循环，但PGE2向胎儿循环的显著转运并不存在。9-酮还原酶途径未导致PGE2向PGF2α的显著相互转化。免疫印迹检测显示胎盘PGDH表达较高。该PGDH定位于胎儿-母体界面的整个合体滋养层以及绒毛外滋养层细胞。PGDH在此部位的存在有助于稳定胎盘主要PG的输出，同时作为屏障阻止其向胎儿循环转运，从而使胎儿和母体的PG内环境稳定得以分离。
