Ethanol has direct effects on human choriocarcinoma cell steroid hormone secretion

Clinical observations indicate that ethanol (EtOH) consumption has significant detrimental effects on pregnancy. However, there is a paucity of information on effects of EtOH on human placental function. We have used JEG choriocarcinoma cells that have many of the functional capabilities of syncytiotrophoblasts, as a model to study direct effects of EtOH on placental function. Between 20-100 mM EtOH decreased rate of cell growth by 25%, but no decrease in [35S]methionine incorporation into protein was noted. EtOH decreased in a dose-dependent manner the secretion of progesterone (P4) in response to cAMP when added with cAMP or when cells were pretreated with EtOH for 2 days. But after 4 or 6 days of pretreatment with EtOH, the P4 response to cAMP was increased by EtOH. Furthermore, EtOH increased the stimulation of P4 secretion by Forskolin. The development of this response was dependent on the period of exposure to EtOH. EtOH also increased estradiol (E2) secretion by unstimulated JEG cells in a dose- and time-dependent manner and increased cAMP stimulated E2 secretion > 2-fold following 4 days of pretreatment with EtOH. These results suggest that EtOH may directly alter hormone secretion by placental cells and such perturbations of endocrine function of the placenta may be responsible for some of the effects of EtOH on pregnancy.