Cigarette smoke extract enhances oxytocin-induced rhythmic contractions of rat and human preterm myometrium

Although smoking during pregnancy is a major risk factor for preterm delivery, the underlying mechanism by which smoking stimulates uterine contractions is still poorly understood. In the present study, we tried to clarify the effects of smoking on myometrial contractility induced by oxytocin (OT) using cigarette smoke extract (CSE). Myometrial strips, which were taken from the rat on day 16 of pregnancy, and from human preterm and term delivery groups, were incubated overnight with several doses of CSE at 37 8C under non-hormonal conditions. The uterine contractile sensitivity and activity (force and frequency) upon exposure to OTwere investigated. Furthermore, the expression levels of oxytocin receptor (OTR) mRNA in the myometrial strips were investigated by real-time PCR. Contractile sensitivity to OT in the rat CSE (10 K7 pieces/ml) group was found to be significantly higher than in the control group (P!0.05). Contractile activity did not differ between the CSE and control groups. The expression levels of rat OTR mRNA in the CSE (10 K7 pieces/ml) group were significantly higher than in the control group (P!0.01). Similarly, in preterm myometrial strips, the expression levels of human OTR mRNA in the CSE (10 K7 pieces/ml) group were significantly higher than in the control group (P!0.05). These findings suggest that CSE directly increases the contractile sensitivity of preterm myometrium in response to OT by upregulating the expression of OTR mRNA and thereby increases the risk of preterm delivery in women, who smoke during pregnancy.