title: Neonatal overfeeding induces early decline of the ovarian reserve: Implications for the role of leptin.
abstract: Early life nutrition is crucial for reproduction. Overweight and obese girls are more likely to experience early menarche, increasing the risk of adult disease. We have previously demonstrated neonatal overfeeding in the rat leads to accelerated growth, early puberty and increased circulating levels of leptin, an adipocyte-derived hormone that regulates puberty. However, the long-term consequences of accelerated puberty and metabolic dysfunction on ovarian reserve are unknown. Here we show that neonatal overfeeding reduced the number of ovarian follicles in adult rats; specifically, the primordial follicle pool was reduced compared to controls. The reduction of ovarian reserve coincided with a diminished release of pituitary gonadotropins at ovulation and altered expression of ovarian markers important for follicular recruitment and survival. These changes were associated with increased levels of ovarian leptin and its receptor. Postnatal administration of leptin antagonist did not reverse the weight gain induced by early life overfeeding, but rescued the decline in the primordial follicle pool and abolished the differences in circulating leptin and gonadotropins. Our findings suggest that the acute effects of elevated circulating leptin may be responsible for the long-term reproductive outcomes after neonatal overfeeding, leading to premature ovarian ageing and changes in reproductive efficiency.
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Melbourne, Australia. Electronic address: luba.sominsky@rmit.edu.au.
authors.forename: Luba
authors.initials: L
authors.lastname: Sominsky
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Melbourne, Australia.
authors.forename: Ilvana
authors.initials: I
authors.lastname: Ziko
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Melbourne, Australia.
authors.forename: Alita
authors.initials: A
authors.lastname: Soch
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth, Australia.
authors.forename: Jeremy T
authors.initials: JT
authors.lastname: Smith
authors.affiliation: School of Health and Biomedical Sciences, RMIT University, Melbourne, Australia.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Spencer
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D006062:Gonadotropins / Q000378:metabolism; D020738:Leptin / Q000097:blood*; D065851:Ovarian Reserve / Q000502:physiology*; D010053:Ovary / Q000378:metabolism / Q000502:physiology*; D050177:Overweight / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D010060:Ovulation / Q000097:blood / Q000378:metabolism / Q000502:physiology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012098:Reproduction / Q000502:physiology*; D012741:Sexual Maturation / Q000502:physiology
chemical_list: D006062:Gonadotropins; D020738:Leptin
keywords: Developmental programming; Leptin; Neonatal overfeeding; Obesity; Ovarian reserve; Primordial follicles