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

• Published in: Endocrine Vol. 53; no. 1; pp. 258 - 270
• Main Authors: Ambrosetti, Valery, Guerra, Marcelo, Ramírez, Luisa A., Reyes, Aldo, Álvarez, Daniela, Olguín, Sofía, González-Mañan, Daniel, Fernandois, Daniela, Sotomayor-Zárate, Ramón, Cruz, Gonzalo
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.07.2016
• Subjects: Androstenedione - blood; Animals; Body Weight - physiology; Cytochrome P-450 CYP3A - metabolism; Diabetes; Diet, High-Fat; Endocrinology; Estradiol - blood; Estriol - blood; Female; Follicle Stimulating Hormone - blood; Humanities and Social Sciences; Insulin - blood; Internal Medicine; Liver - metabolism; Luteinizing Hormone - blood; Maternal Nutritional Physiological Phenomena; Medicine; Medicine & Public Health; multidisciplinary; Obesity - blood; Obesity - metabolism; Original Article; Pregnancy; Prenatal Exposure Delayed Effects - blood; Prenatal Exposure Delayed Effects - metabolism; Rats; Rats, Sprague-Dawley; Science; Sexual Maturation - physiology; Ovary; Maternal obesity; CYP3A2; Estradiol
• ISSN: 1355-008X; 1559-0100
• DOI: 10.1007/s12020-016-0858-0

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.