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Effects of rosiglitazone on ovarian function and fertility in animals with reduced fertility following fetal and neonatal exposure to nicotine

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Abstract

We have previously shown that in utero nicotine exposure causes impaired fertility, follicle immaturity, and ovarian dysfunction in adult female rat offspring. These characteristics overtly resemble the clinical profile of polycystic ovarian syndrome (PCOS) and recent studies have shown that thiazolidinediones such as rosiglitazone improve fertility in women with PCOS but the mechanism is not well defined. Our goal was to examine whether rosiglitazone would (1) ameliorate the altered ovarian physiology that occurs following fetal and neonatal exposure to nicotine and (2) to examine whether this could be due to normalization of ovarian vascularization. At weaning, offspring of nicotine-exposed dams were given either vehicle (NV) or rosiglitazone (3 mg kg−1 day−1; NR). Offspring of saline-exposed dams received vehicle (SV). Tissues were collected when the female offspring reached 26 weeks of age. NV animals had reduced granulosa cell proliferation and increased ovarian cell apoptosis. Treatment with rosiglitazone increased proliferation, and decreased apoptosis, compared NV animals. NV animals had decreased ovarian vascularity relative to controls, whereas NR animals had an intermediate level of ovarian vessel density. Moreover, ovaries from NV animals had decreased levels of the pro-angiogenic growth factors vascular endothelial growth factor (VEGF) and endocrine gland-derived VEGF both of which were increased with rosiglitazone treatment. Rosiglitazone reversed some of the nicotine effects in the ovary and increased ovarian vascularization, follicle maturation and improved oocyte competence. Rosiglitazone may be an important treatment option for PCOS and the present study provides a potential mechanism by which rosiglitazone may have beneficial effects on fertility in these patients.

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Acknowledgements

This work was supported by a research grant from GlaxoSmithKline to ACH and HCG, and the Natural Sciences and Engineering Research Council of Canada and Canadian Institutes for Health Research (JP). Dr. Gerstein holds the Population Health Institute Chair in Diabetes Research (sponsored by Aventis). CEC was funded by a CIHR Strategic Training Program in Tobacco Research Fellowship. We thank Michelle Ross, Ms Sandra Stals and the staff of the McMaster University CAF for their excellent technical assistance.

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Authors and Affiliations

  1. Department of Biomedical Sciences, University of Guelph, Guelph, ON, N1G 2W1, Canada

    J. J. Petrik

  2. Department of Medicine, McMaster University, Hamilton, ON, L8N 3Z5, Canada

    H. C. Gerstein

  3. Reproductive Biology Division, Department of Obstetrics and Gynecology, McMaster University, Hamilton, ON, L8N 3Z5, Canada

    C. E. Cesta, L. D. Kellenberger & A. C. Holloway

  4. Institut National de la Santé et de la Recherche Médicale, U 878, Grenoble, France

    N. Alfaidy

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Correspondence to J. J. Petrik.

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Petrik, J.J., Gerstein, H.C., Cesta, C.E. et al. Effects of rosiglitazone on ovarian function and fertility in animals with reduced fertility following fetal and neonatal exposure to nicotine. Endocr 36, 281–290 (2009). https://doi.org/10.1007/s12020-009-9229-4

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  • DOI: https://doi.org/10.1007/s12020-009-9229-4

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