Ethanol and mitotic inhibitors promote differentiation of trophoblastic cells.
Chronic ethanol abuse during pregnancy can cause fetal injury. A contributing factor in this fetal injury may be the effect of ethanol on the placenta. Ethanol treatment increases human chorionic gonadotropin (hCG) production by cultured human placental trophoblasts. In this study, we show that ethanol treatment reduces total DNA and total protein while stimulating hCG production in term trophoblasts. Ethanol treatment inhibits growth in rapidly proliferating trophoblastic cells from a first trimester placenta and JEG-3 choriocarcinoma cells. In both cell types, the normal increases in total DNA were inhibited in an ethanol dose-dependent manner. Normal increases in total protein were inhibited as well. In contrast, hCG production, an indicator of differentiation, was stimulated by ethanol treatment. Treatment of JEG-3 cells with antimitogenic agents, methotrexate (MTX) or cytosine arabinoside (Ara-C), inhibited cell growth as indicated by decreased total DNA and total protein accumulation. Similar to that with ethanol treatment, inhibition of cell proliferation was accompanied by increases in hCG production. Taken together, these data suggest that one mechanism by which ethanol increases hCG production in human placental trophoblasts may involve alterations in cellular growth and/or differentiation; such alterations may also occur in other proliferating cells in the growing fetus.
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, New York 11030, USA.
P I
PI
Karl
B
B
Harvey
S E
SE
Fisher
D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002822:Choriocarcinoma; D006063:Chorionic Gonadotropin / Q000378:metabolism; D003561:Cytarabine / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008727:Methotrexate / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects*; D010920:Placenta / Q000187:drug effects; D011247:Pregnancy; D014327:Trophoblasts / Q000187:drug effects*; D014594:Uterine Neoplasms
D006063:Chorionic Gonadotropin; D003561:Cytarabine; D000431:Ethanol; D008727:Methotrexate