Early life overfeeding programs reproductive development in the female rat

Abstract

Early life nutrition is crucial for the development of the hypothalamic-pituitary-gonadal (HPG) axis. Overweight and obese girls are significantly more likely to experience early menarche. Together, childhood obesity and precocious puberty have deleterious impact on adult health. Our laboratory has demonstrated that neonatal overfeeding, whereby rats are suckled in small litters (of 4; SL), compared to those suckled in control litters (of 12; CL), results in accelerated growth, advanced onset of puberty, as well as altered peripheral and central immune profiles, including increased levels of circulating leptin. Leptin, an adipocyte-derived hormone and pro-inflammatory cytokine, is essential to the establishment of the hypothalamic neural circuits controlling food intake, along with its critical role in reproductive physiology at all levels of the HPG axis. Here, we examined the role of leptin and its receptor in the prepubertal and adult ovary, along with other indices of ovarian follicular maturation and function. Neonatal overfeeding (SL) differentially altered the expression of the leptin receptor in the neonatal and adult ovary, potentially reflective of developmental and functional differences. Moreover, neonatally overfed females exhibited alterations in other markers of ovarian function, indicative of advanced follicular maturation and therefore a potential for premature reproductive senescence. Our data suggest neonatal overfeeding alters leptin-mediated development of the HPG axis, potentially leading to long-term changes in reproductive efficiency.