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.

Reproductive evaluations in female rat offspring exposed to metformin during intrauterine and intrauterine/lactational periods.

Metformin (MET) is a widely-used drug for the treatment of type 2 diabetes mellitus and gestational diabetes. It is known that metformin crosses the placenta and can to be transferred through milk. In vitro studies show that MET decreases gonadotropin-releasing hormone and gonadotropins release in rat neurons, and decreases progesterone and estradiol in rat granulosa cells and androstenedione synthesis in human theca cells.