Ethanol alters hormone production in cultured human placental trophoblasts.
Maternal alcohol abuse during pregnancy can lead to abnormalities in fetal development, including the fetal alcohol syndrome (FAS). Although intrauterine growth retardation is a hallmark of FAS, the pathophysiology is not fully understood. A contributing factor may be altered placental function, which could affect fetal growth and development. As a major endocrine organ during pregnancy, changes in the production of placental hormones could affect pregnancy and possibly fetal development. In this study, the effect of continued exposure to ethanol on placental hormone production was examined using cultured human placental trophoblasts. Ethanol exposure involved diffusion of ethanol from the atmosphere into the culture medium. This was refreshed daily, leading to daily peak concentrations of 280 to 300 mg/dl (60-65 mM) at 16 to 24 hr. This ethanol exposure for 2 or 4 days significantly increased the production of human chorionic gonadotropin and progesterone by the cultured trophoblasts. However, ethanol treatment had no effect on human placental lactogen production. Acute stimulation (10 min) of cultured trophoblasts with adenosine (50 microM) normally results in increased production of cyclic adenosine 3',5'-monophosphate (cAMP). With ethanol exposure, adenosine-stimulated cAMP production was significantly elevated relative to that in controls. However, the effect of ethanol on adenosine-stimulated cAMP did not appear to be secondary to chronic alterations in adenosine in the culture medium. Measurement of adenosine in the culture medium revealed no difference in concentration or production between control and ethanol treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Karl
P I
PI
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, New York 11030.
Fisher
S E
SE
D000241:Adenosine / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000096:biosynthesis; D000242:Cyclic AMP / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology*; D005317:Fetal Growth Retardation / Q000473:pathology*; D006801:Humans; D007231:Infant, Newborn; D010926:Placental Hormones / Q000096:biosynthesis*; D010928:Placental Lactogen / Q000096:biosynthesis; D011247:Pregnancy; D011374:Progesterone / Q000096:biosynthesis; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects*
D006063:Chorionic Gonadotropin; D010926:Placental Hormones; D000431:Ethanol; D011374:Progesterone; D010928:Placental Lactogen; D000242:Cyclic AMP; D000241:Adenosine