Neonatal overfeeding reduces estradiol plasma levels and disrupts noradrenergic-kisspeptin-GnRH pathway and fertility in adult female rats

This work evaluated the effects of neonatal overfeeding, induced by litter size reduction, on fertility and the noradrenaline-kisspeptin-gonadotrophin releasing hormone (GnRH) pathway in adult female rats. The litter size was adjusted to 3 pups with each mother in the small litters (SL) and 10 pups with each mother in the normal litters (NL). SL females exhibited metabolic changes associated with reproductive dysfunctions, shown by earlier vaginal opening and first estrus, later regular cyclicity onset, and lower and higher occurrences of estrus and diestrus phases, respectively, as well as reduced fertility, estradiol plasma levels, and mRNA expressions of tyrosine hydroxylase in the locus coeruleus, kisspeptin, and GnRH in the preoptic area in adult females in the afternoon of proestrus. These results suggest that neonatal overfeeding in female rats promotes reproductive dysfunctions in adulthood, such as lower estradiol plasma levels associated with impairments in fertility and noradrenaline-kisspeptin-GnRH pathway during positive feedback. Graphical Abstract. Schematic diagram demonstrating that neonatal overfeeding induced by litter size reduction in female rats caused metabolic alterations: higher body weight, Lee index, adiposity, free fatty acids and corticosterone plasma levels, and glucose intolerance. These effects were associated with reproductive dysfunctions: earlier vaginal opening and first estrus, delayed estrous cycle regularization, estrous cycle dysregulation, as well as lower plasma estradiol concentrations related to reduced fertility and tyrosine hydroxylase (TH) mRNA expression in the locus coeruleus (LC), and kisspeptin (Kiss) and gonadotropin releasing hormone (GnRH) mRNA expression in the preoptic area (POA) in adult females in the afternoon of proestrus. [Display omitted] •Litter size reduction induced reproductive dysfunctions in female rats.•Obesity induced by neonatal overnutrition advanced puberty in females.•Reduction of litter size caused dysregulation of estrous cycle.•Neonatal overnutrition reduced estradiol plasma levels and fertility.