The placenta, PGE2 and parturition.

Abstract

It is proposed that prostaglandin E2 (PGE2), secreted by the fetal placenta of the sheep, acts as a circulating regulator of the physiological function of many fetal organs (tissue) in a way analogous to catecholamines in the adult. The specificity of PGE2 action in different tissues is determined by three different receptor subtypes which regulate intracellular calcium concentrations via the IP3 pathway, or cyclic AMP concentrations via the adenylcyclase system. The placenta, by secreting PGE2 (and possibly other factors such as adenosine), modifies the function of key organ systems allowing the fetus to survive and develop in the aqueous environment of the uterus. During fetal development, fetal organs and metabolic pathways can mature while their function is suppressed by placental PGE2. At birth, by ligating the cord and removing the placenta as the source of these inhibitory substances, the newborn is able to adapt readily to its new environment with fully-functional, mature organ systems. This paper discusses how placental PGE2 may regulate fetal breathing movements, whether the removal of placental PGE2 is involved in the initiation of continuous breathing at birth, and whether it suppresses the activity of the peripheral chemoreceptors during fetal life. The ability of PGE2 to maintain a widely patent ductus arteriosus, to suppress non-shivering thermogenesis, to stimulate fetal insulin secretion and to suppress the hepatic gluconeogenic pathway in the fetus is also discussed. Finally, the ability of PGE2 to activate the fetal hypothalamo-pituitary-adrenal axis is discussed, raising the possibility that the placenta also plays a key role in the initiation of birth in this species.