title: Effect of cigarette smoking on mRNA and protein levels of oxytocin receptor and on contractile sensitivity of uterine myometrium to oxytocin in pregnant women.
abstract: OBJECTIVE
  Although smoking is the most important modifiable risk factor associated with preterm delivery, the underlying mechanism by which smoking stimulates premature uterine contractions is still poorly understood. In the present study, we investigated whether cigarette smoking affects the contractile sensitivity of uterine myometrium to oxytocin in pregnant women.
  
  
  METHODS
  Cigarette smoking habits of pregnant women were evaluated by direct interviews and by measuring exhaled carbon monoxide (CO). We isolated myometrial strips from pregnant smokers and non-smokers and evaluated uterine contractile sensitivity to oxytocin. Gene expression levels of oxytocin receptors (OTR) were compared between myometrial strips obtained from smokers and non-smokers by real-time PCR. OTR protein levels in the myometrium were evaluated by Western blotting.
  
  
  RESULTS
  The reported number of cigarettes smoked per day by the interviewee significantly correlated with the concentration of exhaled CO. Oxytocin sensitivity increased significantly in smokers (n=6) compared with non-smokers (n=11). Real-time PCR analysis did not reveal any significant difference in OTR mRNA expression between smokers and non-smokers. Western blotting revealed that OTR level was significantly increased in smokers compared with non-smokers. Both number of cigarettes smoked per day and the concentration of exhaled CO correlated with oxytocin sensitivity.
  
  
  CONCLUSIONS
  Our findings suggest that smoking increases oxytocin sensitivity of pregnant myometrium by increasing OTR levels even though OTR mRNA expression remains unaltered, thereby increasing the risk of preterm delivery in women who smoke during pregnancy. The sensitivity is dependent on number of cigarettes smoked per day.
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Takii Hospital, Kansai Medical University, Osaka, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kanamori
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Takii Hospital, Kansai Medical University, Osaka, Japan. Electronic address: yasuda@takii.kmu.ac.jp.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yasuda
authors.affiliation: Department of Obstetrics and Gynecology, Affiliated Takii Hospital, Kansai Medical University, Osaka, Japan.
authors.forename: Genichiro
authors.initials: G
authors.lastname: Sumi
authors.affiliation: Division of Cardiology, Department of Medicine II, Kansai Medical University, Osaka, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tsuzuki
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan.
authors.forename: Hisayuu
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Okada
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Medical University, Osaka, Japan.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Kanzaki
mesh_terms: D000328:Adult; D002248:Carbon Monoxide / Q000378:metabolism; D005260:Female; D006801:Humans; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism; D007752:Obstetric Labor, Premature / Q000209:etiology; D010121:Oxytocin / Q000494:pharmacology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000096:biosynthesis*; D012907:Smoking / Q000503:physiopathology*; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: D012333:RNA, Messenger; D018045:Receptors, Oxytocin; D010121:Oxytocin; D002248:Carbon Monoxide
keywords: Cigarette smoking; Oxytocin receptor sensitivity; Uterine myometrium; microRNAs