Placental Transport in Early Pregnancy—A Workshop Report

Abstract

Most studies concerning placental transport in humans have concentrated on term placenta, undoubtedly because this tissue is more readily available than from earlier in pregnancy. As a result, our understanding of placental transport in early pregnancy is somewhat limited. Certainly this aspect of placental physiology needs exploring, not least because in early pregnancy both the fetus and the developing placenta will have changing metabolic demands for nutrients/metabolites. Additionally, the uterine environment in which the placenta is developing in early pregnancy is also changing concomitantly. This is especially notable with respect to the partial pressure of oxygen (pO 2 ) in the intervillous space (IVS), which is raised following the onset of blood flow to the IVS after progressive dislocation of trophoblast plugs from the openings of the spiral arterioles at 10‐12 weeks of pregnancy [1]. This leads us to consider several questions. How is fetal nutrition mediated in early pregnancy before the onset of blood flow to the IVS? What is the impact of the changing oxygen environment on placental transport processes? What placental transporters are expressed in first trimester and how might these be regulated? What is the relative importance of transcellular and paracellular pathways of transport during early pregnancy and how might these change with advancing gestation? The aim of this workshop was to address these issues with a view to gaining a better understanding of placental transport events in early pregnancy. Graham Burton (Cambridge) started by reviewing the placental environment during the first trimester. During the first week of development, the embryo most likely obtains nutrients by simple diffusion from blood pooled in the trophoblastic lacunae. However, the metabolic demands of the developing embryo soon outstrip this means of nutrient delivery and progressive placental development and the establishment of uteroplacental and fetoplacental circulations provides a more efficient means of maternofetal exchange. However, before 8 weeks of pregnancy, no maternal arterial connections with the IVS space exist, and endovascular extravillous trophoblast occlude the openings of spiral arteries. But from 10 weeks onwards direct communication between the spiral arteries and the IVS could be delineated [2]. The intervillous circulation is, however, not continuous over the whole placenta until about after 12 weeks [1]. So, how does the fetus obtain nutrients prior to the establishment of the maternal circulation through the placenta allowing haemotrophic nutrition to occur? One possibility is that a plasma filtrate percolates through the arterial plugs into the IVS providing a source of nutrients for histiotrophic nutrition [2]. Another proposal is that carbohydrate-rich uterine glandular secretions, discharged into the IVS are taken up by trophoblastic tissue [2].