Fetal and Neonatal Exposure to Nicotine Disrupts Ovarian Function and Fertility in Adult Female Rats

Reproductive Biology Division, Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, Canada.
Endocrine (Impact Factor: 3.88). 11/2006; 30(2):213-6. DOI: 10.1385/ENDO:30:2:213
Source: PubMed


Women born to mothers who smoked during pregnancy have been shown to have impaired fertility, although the mechanisms underlying this association are unknown. Nicotine administration in adult animals has adverse effects on the ovary and uterus; however, the effects of fetal exposure to nicotine on postnatal ovarian function have not been determined. The goal of this study was to assess the effect of fetal and neonatal exposure to nicotine on ovarian function and fertility of the offspring. Nulliparous female Wistar rats were given 1 nicotine bitartrate, subcutaneously for 14 d prior to mating, during pregnancy and throughout lactation until weaning. Measures of fertility, breeding success, and serum levels of ovarian steroid hormones in offspring were assessed at 4 and 6 mo of age. Fetal and neonatal exposure to nicotine significantly increased the time to pregnancy as the animals aged. Similarly, evidence of altered ovarian steroidogenesis including increased serum progesterone concentrations and a decreased estrogen:progesterone ratio was observed in 6-mo-old animals. We conclude that fetal and neonatal exposure to nicotine results in delayed ovarian dysfunction in adult female offspring.

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    • "In females, a general ovarian toxicity has also been suggested,83141142143144 as in utero exposure to components in cigarette smoke have caused a reduction in the final pool of oocytes and altered ovarian steroidogenesis.142 Lutterodt et al.83141142143144 and Mamsen et al.83141142143144 investigated whether early in utero exposure to cigarette smoking affected the number of oogonia in ovaries from human embryos. "
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    ABSTRACT: Maternal cigarette smoking may affect the intrauterine hormonal environment during pregnancy and this early fetal exposure may have detrimental effects on the future trajectory of reproductive health. In this review, we discuss the epidemiological literature on the association between prenatal exposure to maternal cigarette smoking and several aspects of reproductive health. The literature points towards an increased risk of the urogenital malformation cryptorchidism, but a potential protective effect on the risk of hypospadias in sons following prenatal cigarette smoking exposure. Studies on sexual maturation find a tendency towards accelerated pubertal development in exposed boys and girls. In adult life, prenatally exposed men have impaired semen quality compared with unexposed individuals, but an influence on fecundability, that is, the biological ability to reproduce, is less evident. We found no evidence to support an association between prenatal cigarette smoking exposure and testicular cancer. Among adult daughters, research is sparse and inconsistent, but exposure to cigarette smoking in utero may decrease fecundability. In conclusion, prenatal exposure to cigarette smoking may cause some long-term adverse effects on the reproductive health.
    Asian Journal of Andrology 01/2014; 16(1):39-49. DOI:10.4103/1008-682X.122351 · 2.60 Impact Factor
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    • "(B) The percentage of degenerated seminiferous tubules in 7 week old rats in the saline control group vs. rats with in utero and lactational exposure to nicotine. Each bar represents the mean ± SD. comes including reduced fertility in female offspring [26]; however, the effects on male reproductive tract development have not been reported previously. Results from the present study demonstrate that fetal and neonatal exposure to nicotine has adverse, albeit transient, effects on male reproductive tract development. "
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    ABSTRACT: The objective of this study was to determine the effect of in utero and lactational exposure to nicotine on the male reproductive tract. Dams were randomly assigned to receive saline or nicotine bitartrate (1mg/kg-d s.c.) daily for two weeks prior to mating until weaning (postnatal day 21). Male offspring were sacrificed at 7 (peri-pubertal) and 26 (adult) weeks of age. Nicotine-exposure resulted in retention of spermatids after stage VIII, tubular vacuolation, degeneration of pachytene and round spermatids at stage VII in the testes; and lymphocyte infiltration, germ cell exfoliation, and hypospermia in epididymides, at 7 weeks of age. Nicotine-exposure had no effect on testis or epididymal morphology, daily sperm production, epididymal sperm reserve, sperm viability at 26 weeks of age, and circulating testosterone levels at either age examined. We conclude that maternal nicotine-exposure during pregnancy and lactation can induce transient structural changes in the testis and epididymis of male offspring.
    Reproductive Toxicology 12/2010; 31(4):418-23. DOI:10.1016/j.reprotox.2010.12.004 · 3.23 Impact Factor
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    • "The dose of nicotine used in our animal model results in maternal serum cotinine concentrations of 136 ng/ml (Holloway et al., 2006), which is within the range of cotinine levels reported in women who are considered “moderate smokers” (80–163 ng/ml) (Eskenazi and Bergmann, 1995). In addition, this dose of nicotine results in serum cotinine concentrations of 26 ng/ml in the nicotine-exposed offspring at birth (Holloway et al., 2006), which is also within the range (5–30 ng/ml) observed in infants nursed by smoking mothers (Luck and Nau, 1985). The following sections will evaluate findings from our animal model as well as similar models of developmental nicotine exposure by others in the field. "
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    ABSTRACT: Cigarette smoking during pregnancy is associated with numerous obstetrical, fetal, and developmental complications, as well as an increased risk of adverse health consequences in the adult offspring. Nicotine replacement therapy (NRT) has been developed as a pharmacotherapy for smoking cessation and is considered to be a safer alternative for women to smoking during pregnancy. The safety of NRT use during pregnancy has been evaluated in a limited number of short-term human trials, but there is currently no information on the long-term effects of developmental nicotine exposure in humans. However, animal studies suggest that nicotine alone may be a key chemical responsible for many of the long-term effects associated with maternal cigarette smoking on the offspring, such as impaired fertility, type 2 diabetes, obesity, hypertension, neurobehavioral defects, and respiratory dysfunction. This review will examine the long-term effects of fetal and neonatal nicotine exposure on postnatal health.
    Toxicological Sciences 04/2010; 116(2):364-74. DOI:10.1093/toxsci/kfq103 · 3.85 Impact Factor
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