In Utero and Lactational Exposure to Nicotine Alters the Intra-Ovarian IGF System in Adult Female Rats

Abstract: In humans there is evidence that in utero exposure to cigarette smoke results in decreased fertility in female offspring. We have demonstrated in rats that fetal and neonatal exposure to nicotine alone results in impaired fertility and increased follicular atresia in the adult female offspring. In mammals, the insulin-like growth factor-I and-II (IGF-I and-II) and their binding proteins (IGFBPs) are considered stimulators and inhibitors of follicular growth and maturation. Therefore we hypothesized that dysregulation of the intra-ovarian IGF system could be implicated in the impaired fertility observed in nicotine-exposed offspring. Nulliparous female Wistar rats were exposed to nicotine (1 mg/kg/d) for 2 weeks prior to mating until weaning. Ovaries were collected on the morning of estrus from sexually mature saline- and nicotine-exposed offspring. Protein expression of IGF ligands and receptors (IGFR-I and IGFR-II) were quantifi ed by western blot and immunohistochemistry. The expression of IGF-I, IGF-II; IGFR-I, IGFR-II; and IGFBP1–6 mRNA in the ovary was deter-mined by semi-quantitative reverse transcriptase-PCR. Results showed that nicotine exposure signifi cantly reduced IGF-I, IGF-II and IGFR-I protein expression (p 0.01) relative to saline controls. Furthermore, nicotine-exposed offspring had signifi cantly reduced IGFR-II mRNA expression (p 0.01) in the ovary. Data from this study suggest that the decreased fertility and increased follicular atresia in nicotine-exposed animals may be due, in part, to disruption of IGF regulation i