MATERNAL SMOKING INHIBITS EARLY HUMAN CYTOTROPHOBLAST DIFFERENTIATION

Differentiation of the specialized epithelial cells of the placenta, t ermed cytotrophoblasts, is a particularly important aspect of placenta l development during the first trimester of pregnancy. During this pro cess cytotrophoblast stem cells either fuse to form the syncytium or a ggregate to form cell columns that adhere to, then invade the uterus. We found that chorionic villi from early gestation placentas of mother s who smoke showed a marked reduction in cell columns, a defect that c ould not be corrected by placing them in culture. We used two differen t in vitro models to determine if nicotine plays a role in the etiolog y of this defect. Exposing early gestation chorionic villi from nonsmo king women to nicotine inhibited subsequent cell column formation in v itro. Nicotine also inhibited normal first trimester cytotrophoblast i nvasion, apparently by reducing the ability of treated cells to synthe size and activate the 92 kDa type IV collagenase, an important mediato r of invasion in vitro. These results suggest that maternal cigarette smoking inhibits the trophoblast differentiation pathway that leads to column formation and uterine invasion. This effect, which is due at l east in part to the effects of nicotine, may contribute to the growth retardation observed in fetuses of mothers who smoke during pregnancy.