Postnatal undernutrition increases estradiol plasma levels and sexual receptivity and disrupts the kisspeptin-GnRH pathway in adult female rats

Abstract

Undernutrition has increased worldwide in recent years and it is known that environmental factors to which individuals are exposed in early life can result in metabolic and reproductive changes that remain in adult life. In this context, the litter size expansion is a classic model used to induce undernutrition early in development. Thus, this study aimed to evaluate the effects of neonatal undernutrition induced by the litter size expansion on metabolic and reproductive parameters of female rats. At birth, litter size was adjusted to large (LL - 16 pups) and normal (NL - 10 pups) litters. After weaning, the feed was offered ad libitum and the animals were euthanized from postnatal day 90, when in proestrus. Neonatal undernutrition resulted in lower body weight from weaning to adulthood, although food intake remained higher in the LL group in this period. These animals exhibited a delayed onset of puberty, demonstrated by a late first estrus, increased values of circulating estradiol, luteinizing hormone, follicle-stimulating hormone, and number of antral follicles in the ovaries, associated with higher sexual receptivity, without differences in maternal behavior. The LL group also exhibited decreased messenger RNA (mRNA) expression of kisspeptin and gonadotropin-releasing hormone (GnRH) in the preoptic area, without changes in the mRNA expression of GnRH receptor in the pituitary. These results demonstrate that moderate undernutrition in the lactational period promotes metabolic changes associated with impairments in the kisspeptin-GnRH pathway, without compromising maternal behavior and peripheral reproductive functions such as estrous cyclicity, sexual receptivity, and fertility.