title: Nicotine, but not cotinine, has a direct toxic effect on ovarian function in the immature gonadotropin-stimulated rat.
abstract: PMSG-primed and hCG-triggered rat ovaries were exposed to nicotine and its major metabolite, cotinine, using in vitro and in vivo experimental approaches. In vivo, a dose-dependent reduction in oocytes within the fallopian tube was noted in nicotine treated rats (6.25 ng/g animal weight, P < 0.001). Serum estradiol concentrations were also reduced in rats receiving nicotine (P < 0.04). There were no significant differences in weight gain. Cotinine had no effects. In vitro, nicotine also caused a dose-dependent reduction in oocytes in the collection chamber (P < 0.0001). Estradiol levels in nicotine-treated perfusions were reduced and reached statistical significance at 7 h (P < 0.003). The in vitro fertilization rate was reduced for nicotine-treated perfusions exposed to 1.43 pg/mL of nicotine (P < 0.001). Cotinine had no effect in vitro. We conclude that nicotine inhibits ovulation, estradiol production, and fertilization both in vivo and in vitro in rat models of ovulation. Cotinine did not affect these parameters. These effects of nicotine are notably independent of nicotine's known effect on the midcycle gonadotropin surge.
authors.affiliation: Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City 84132.
authors.forename: C W
authors.initials: CW
authors.lastname: Blackburn
authors.forename: C A
authors.initials: CA
authors.lastname: Peterson
authors.forename: H A
authors.initials: HA
authors.lastname: Hales
authors.forename: D T
authors.initials: DT
authors.lastname: Carrell
authors.forename: K P
authors.initials: KP
authors.lastname: Jones
authors.forename: R L
authors.initials: RL
authors.lastname: Urry
authors.forename: C M
authors.initials: CM
authors.lastname: Peterson
mesh_terms: D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003367:Cotinine / Q000633:toxicity*; D004958:Estradiol / Q000097:blood; D005260:Female; D005306:Fertilization / Q000187:drug effects; D006062:Gonadotropins / Q000494:pharmacology*; D006064:Gonadotropins, Equine / Q000494:pharmacology; D009538:Nicotine / Q000633:toxicity*; D009865:Oocytes / Q000187:drug effects; D010053:Ovary / Q000166:cytology / Q000187:drug effects*; D010060:Ovulation / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects
chemical_list: D006063:Chorionic Gonadotropin; D006062:Gonadotropins; D006064:Gonadotropins, Equine; D011374:Progesterone; D004958:Estradiol; D009538:Nicotine; D003367:Cotinine