NICOTINE, BUT NOT COTININE, HAS A DIRECT TOXIC EFFECT ON OVARIAN-FUNCTION IN THE IMMATURE GONADOTROPIN-STIMULATED RAT

PMSG-primed and hCG-triggered rat ovaries were exposed to nicotine and its major metabolite, cotinine, using in vitro and in vivo experiment al approaches. In vivo, a dose-dependent reduction in oocytes within t he 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 diffe rences in weight gain. Cotinine had no effects. In vitro, nicotine als o caused a dose-dependent reduction in oocytes in the collection chamb er (P < 0.0001). Estradiol levels in nicotine-treated perfusions were reduced and reached statistical significance at 7 h (P < 0.003). The i n 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 pro duction, 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 mid cycle gonadotropin surge.