Smoking Enhances Oxytocin-Induced Rhythmic Myometrial Contraction1

Abstract

Although smoking during pregnancy is one of the major risk factors of premature delivery, the underlying mechanism by which smoking causes premature delivery is unknown. In the present study, we examined the effects of smoking on uterine contractility induced by oxytocin and prostaglandin F(2alpha). Rats inhaled either cigarette smoke or room air from Day 14 to Day 16 of pregnancy through an inhalation apparatus for experimental animals (type "Hamburg II"). After the rats were killed on Day 17 of pregnancy, the uterine contractile sensitivity and activity on exposure to oxytocin or prostaglandin F2alpha were investigated. The expression levels of oxytocin-receptor mRNA and prostaglandin F(2alpha) receptor mRNA in the uterus were investigated by reverse transcription-polymerase chain reaction. The contractile activity was assessed as the contractile force and the frequency of rhythmic contractions of myometrial strips that were treated with oxytocin or prostaglandin F(2alpha). The contractile sensitivity to oxytocin was significantly higher in the smoking group than in the control group (P < 0.01). Although the contractile force of oxytocin-induced contractions did not differ between the smoking and control groups, the frequency of contractions was significantly higher in the smoking group than in the control group (P < 0.01). On the other hand, no significant differences were found in the contractile sensitivity and activity in response to prostaglandin F(2alpha) between the smoking and control groups. The expression of oxytocin-receptor mRNA in the myometrium was significantly increased in the smoking group compared with the control group (P < 0.01). However, no significant difference was found in the level of expression of prostaglandin F(2alpha)-receptor mRNA between the two groups. These results suggest that smoking during pregnancy increases the contractile sensitivity and activity of the myometrium in response to oxytocin by up-regulating the expression of oxytocin-receptor mRNA. The effects of smoking on the contractile sensitivity and activity of the myometrium in response to oxytocin may increase the risk of premature delivery in smokers.

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

“…Although the mechanisms through which cigarette smoke cause preterm uterine contractions and preterm delivery have not been known, it is well known that OT and PG F 2a induce pregnant uterine contractions and preterm delivery (Takahashi et al 1980, Fuchs et al 1984, Ivanisevic et al 2001. We have recently demonstrated that inhalation of cigarette smoke for 3 days (seven cigarettes/day) by pregnant Wistar rats significantly reduces both fetal and placental weight (Egawa et al 2003), and confirmed that smoking during pregnancy is an important cause of low birth weight, as has often been reported. We have also demonstrated that the sensitivity of pregnant rat uterus to OT (but not PG F 2a ) was significantly increased in the smoking group in comparison with the control group, and the expression of OTR mRNA, but not FP mRNA, in the uterus was significantly increased in the smoking group (Egawa et al 2003).…”

“…We have recently demonstrated that inhalation of cigarette smoke for 3 days (seven cigarettes/day) by pregnant Wistar rats significantly reduces both fetal and placental weight (Egawa et al 2003), and confirmed that smoking during pregnancy is an important cause of low birth weight, as has often been reported. We have also demonstrated that the sensitivity of pregnant rat uterus to OT (but not PG F 2a ) was significantly increased in the smoking group in comparison with the control group, and the expression of OTR mRNA, but not FP mRNA, in the uterus was significantly increased in the smoking group (Egawa et al 2003). However, it remains unclear whether the inhalation of cigarette smoke directly enhances the expression of OTR mRNA in the myometrium.…”

“…We have recently reported that 3 days of inhalation of cigarette smoke by pregnant rats (days 14-16) increases contractile sensitivity and activity of the myometrium upon exposure to OT, but not to PG F 2a (Egawa et al 2003). Additionally, we have indicated that the expression of OTR mRNA, but not FP mRNA, in rat myometrium is increased by the inhalation of cigarette smoke (Egawa et al 2003).…”

“…Additionally, we have indicated that the expression of OTR mRNA, but not FP mRNA, in rat myometrium is increased by the inhalation of cigarette smoke (Egawa et al 2003). Therefore, the increased contractile sensitivity and activity of pregnant myometrium in response to OT may result from the increased expression of OTR mRNA caused by smoking and increase the risk of preterm delivery in smokers.…”

“…The contractile sensitivity and activity of myometrium were evaluated by a previously described method (Egawa et al 2003). Briefly, each strip after the overnight incubation under one of the several conditions was attached to a holder under a 1 g resting tension.…”