ETHANOL AND MITOTIC INHIBITORS PROMOTE DIFFERENTIATION OF TROPHOBLASTIC CELLS

Chronic ethanol abuse during pregnancy can cause fetal injury. A contr ibuting factor in this fetal injury may be the effect of ethanol on th e placenta. Ethanol treatment increases human chorionic gonadotropin ( hCG) production by cultured human placental trophoblasts. In this stud y, we show that ethanol treatment reduces total DNA and total protein while stimulating hCG production in term trophoblasts. Ethanol treatme nt inhibits growth in rapidly proliferating trophoblastic cells from a first trimester placenta and JEG-3 choriocarcinoma cells. In both cel l types, the normal increases in total DNA were inhibited in an ethano l dose-dependent manner. Normal increases in total protein were inhibi ted as well. In contrast, hCG production, an indicator of differentiat ion, was stimulated by ethanol treatment. Treatment of JEG-3 cells wit h antimitogenic agents, methotrexate (MIX) or cytosine arabinoside (Ar a-C), inhibited cell growth as indicated by decreased total DNA and to tal protein accumulation. Similar to that with ethanol treatment, inhi bition of cell proliferation was accompanied by increases in hCG produ ction. Taken together, these data suggest that one mechanism by which ethanol increases hCG production in human placental trophoblasts may i nvolve alterations in cellular growth and/or differentiation; such alt erations may also occur in other proliferating cells in the growing fe tus.