Oestradiol stimulates morphological and functional differentiation of human villous cytotrophoblast

Trophoblast differentiation is a complex process involving interactions of cytotrophoblastic cells with their evolutive milieu. During pregnancy, the fete-placental unit produces large amounts of steroids. Progesterone and oe stradiol are increasingly produced when the syncytiotrophoblast is highly d ifferentiated. Furthermore, receptors to these hormones are expressed by th e trophoblast. This led us to test the hypothesis that steroid production c ould affect the morphological and functional differentiation of the trophob last during gestation. The fusion of cytotrophoblastic cells into syncytiotrophoblast was assessed using fluorescence recovery after photobleaching for gap junctional commun ication analysis (gap-FRAP), desmoplakin immunostaining and connexin 43 exp ression. In parallel, functional differentiation was assessed by beta-human chorionic gonadotrophin (beta hCG) production and human chorionic somatoma mmotropin (hCS) expression analysis. The presence of oestradiol, 1 mu M, in creased the percentage of coupled cells (3.8-fold), connexin 43 expression and stimulated the syncytium formation. In parallel, oestradiol (1, 3 and 5 mu M) induced a significant increase in the daily hCG production. The ster oid action was specific, as the stimulatory effects were inhibited by tamox ifen. Oestradiol also stimulated hCS expression (51 per cent compared to co ntrol after 3 days). As trophoblastic differentiation is specifically stimu lated by hCG, oestradiol could act via the stimulation of hCG production or via a direct action. In the presence of an efficient concentration of hCG antibody, oestradiol still stimulated hCS expression, suggesting a self-suf ficient effect of the steroid. Physiological concentrations of progesterone were ineffective in modulating trophoblast differentiation. In conclusion, oestradiol could be implicated in the maturation and aging o f the trophoblast. (C) 1999 Harcourt Publishers Ltd.