Egawa Makoto, Yasuda Katsuhiko, Nakajima Tatsuya, Okada Hidetaka, Yoshimura Tomoo, Yuri Takashi, Yasuhara Masahiro, Nakamoto Tsuyoshi, Nagata Fumie, Kanzaki Hideharu
Department of Obstetrics and Gynecology, Kansai Medical University, Moriguchi, Osaka, 570-0074, Japan.
Biol Reprod. 2003 Jun;68(6):2274-80. doi: 10.1095/biolreprod.102.010785. Epub 2003 Feb 19.
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.
尽管孕期吸烟是早产的主要危险因素之一,但吸烟导致早产的潜在机制尚不清楚。在本研究中,我们研究了吸烟对催产素和前列腺素F(2α)诱导的子宫收缩的影响。从妊娠第14天至第16天,大鼠通过实验动物吸入装置(“汉堡II型”)吸入香烟烟雾或室内空气。在妊娠第17天处死大鼠后,研究子宫对催产素或前列腺素F2α暴露的收缩敏感性和活性。通过逆转录-聚合酶链反应研究子宫中催产素受体mRNA和前列腺素F(2α)受体mRNA的表达水平。收缩活性通过用催产素或前列腺素F(2α)处理的子宫肌条的收缩力和节律性收缩频率来评估。吸烟组对催产素的收缩敏感性显著高于对照组(P < 0.01)。虽然吸烟组和对照组之间催产素诱导收缩的收缩力没有差异,但吸烟组的收缩频率显著高于对照组(P < 0.01)。另一方面,吸烟组和对照组之间对前列腺素F(2α)的收缩敏感性和活性没有显著差异。与对照组相比,吸烟组子宫肌层中催产素受体mRNA的表达显著增加(P < 0.01)。然而,两组之间前列腺素F(2α)受体mRNA的表达水平没有显著差异。这些结果表明,孕期吸烟通过上调催产素受体mRNA的表达增加子宫肌层对催产素的收缩敏感性和活性。吸烟对子宫肌层对催产素的收缩敏感性和活性的影响可能会增加吸烟者早产的风险。