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Increase in endogenous estradiol in the progeny of obese rats is associated with precocious puberty and altered follicular development in adulthood

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Abstract

Maternal obesity during pregnancy has been related with several pathological states in offspring. However, the impact of maternal obesity on reproductive system on the progeny is beginning to be elucidated. In this work, we characterize the effect of maternal obesity on puberty onset and follicular development in adult offspring in rats. We also propose that alterations in ovarian physiology observed in offspring of obese mothers are due to increased levels of estradiol during early development. Offspring of control dams and offspring of dams exposed to a high-fat diet (HF) were studied at postnatal days (PND) 1, 7, 14, 30, 60, and 120. Body weight and onset of puberty were measured. Counting of ovarian follicles was performed at PND 60 and 120. Serum estradiol, estriol, androstenedione, FSH, LH, and insulin levels were measured by ELISA. Hepatic CYP3A2 expression was determined by Western blot. HF rats had a higher weight than controls at all ages and they also had a precocious puberty. Estradiol levels were increased while CYP3A2 expression was reduced from PND 1 until PND 60 in HF rats compared to controls. Estriol was decreased at PND60 in HF rats. Ovaries from HF rats had a decrease in antral follicles at PND60 and PND120 and an increase in follicular cysts at PND60 and PND120. In this work, we demonstrated that maternal obesity in rats alters follicular development and induces follicular cysts generation in the adult offspring. We observed that maternal obesity produces an endocrine disruption through increasing endogenous estradiol in early life. A programmed failure in hepatic metabolism of estradiol is probably the cause of its increase.

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Acknowledgments

This work was supported by Fondecyt Initiation Grant 11130707-CONICYT. Additional funds were provided by Center for Neurobiology and Cerebral Plasticity (CNPC)—Universidad de Valparaíso. We thank Dr. Gladys Tapia from University of Chile for helping with hepatic studies and Dr. Alfonso Paredes from University of Chile for kindly providing LH and FSH kits. We thank to Ms. Tania Cerda from University of Valparaíso for technical support.

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    1. Laboratorio de Alteraciones Reproductivas y Metabólicas, Facultad de Ciencias, Centro de Neurobiología y Plasticidad Cerebral (CNPC), Instituto de Fisiología, Universidad de Valparaíso, Av. Gran Bretaña 1111, Playa Ancha, 2360102, Valparaiso, Chile

      Valery Ambrosetti, Marcelo Guerra, Luisa A. Ramírez, Aldo Reyes, Daniela Álvarez, Sofía Olguín & Gonzalo Cruz

    2. Molecular and Clinical Pharmacology Program, Faculty of Medicine, Institute of Biomedical Sciences, University of Chile, 8380492, Santiago, Chile

      Daniel González-Mañan

    3. Programa de Doctorado en Farmacología, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, 8380492, Santiago, Chile

      Daniela Fernandois

    4. Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral (CNPC), Facultad de Ciencias, Instituto de Fisiología, Universidad de Valparaíso, 2360102, Valparaiso, Chile

      Ramón Sotomayor-Zárate

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    Valery Ambrosetti and Marcelo Guerra have contributed equally to this work.

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    Ambrosetti, V., Guerra, M., Ramírez, L.A. et al. Increase in endogenous estradiol in the progeny of obese rats is associated with precocious puberty and altered follicular development in adulthood. Endocrine 53, 258–270 (2016). https://doi.org/10.1007/s12020-016-0858-0

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