The role of oestradiol in embryonic development

Abstract

The present study examines the possible roles of oestradiol and its binding sites in increased early embryo demise in rats after hyperstimulation with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG). Normal 2a??cell rat embryos were cultured in high levels of oestradiol and their development was assessed daily. Antia??oestrogens tamoxifen or 4a??hydroxyandrostenedione (4-OHA) at various doses were injected into females at the time of hyperstimulation and embryo count was performed on day 14 of pregnancy. Confocal microscopy and coumestrol, a fluorescent phytoa??oestrogen, were used to measure the density and distribution of oestrogen-binding sites in live oocytes and prea??implanting embryos, and fixed oviducts and uterine horns throughout the oestrous cycle and early pregnancy (days 1a??6) in both control and hyperstimulated rats. High doses of oestradiol retarded embryonic development and caused their demise. Tamoxifen was more effective than 4-OHA in restoring embryo survival in hyperstimulated animals. Confocal imaging revealed that the oestrogena??binding sites in hyperstimulated oocytes, embryos and reproductive tissues were altered in concentration and localisation when compared with controls. Together, the results obtained support the hypotheses that excessive oestradiol is responsible for the negative effects of hyperstimulation on early embryonic development and that altered expression and distribution of oestrogena??binding sites constitute a mechanism by which oestradiol exerts its actions.