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

Mol Cell Endocrinol. 2021 Mar 15:524:111147. doi: 10.1016/j.mce.2020.111147. Epub 2020 Dec 31.

Abstract

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.

Keywords: Energy homeostasis; Estrous cycle; Litter size reduction; Locus coeruleus; Preoptic area.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Animals
  • Animals, Newborn
  • Blood Glucose / metabolism
  • Brain Stem / pathology
  • Estradiol / blood*
  • Estrous Cycle
  • Female
  • Fertility / physiology*
  • Gonadotropin-Releasing Hormone / genetics
  • Gonadotropin-Releasing Hormone / metabolism*
  • Gonads / pathology
  • Hypothalamus / pathology
  • Kisspeptins / metabolism*
  • Lipids / blood
  • Litter Size
  • Male
  • Norepinephrine / metabolism*
  • Overnutrition / blood*
  • Overnutrition / metabolism*
  • Pituitary Gland / pathology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Sexual Maturation
  • Weight Gain

Substances

  • Blood Glucose
  • Kisspeptins
  • Lipids
  • RNA, Messenger
  • Gonadotropin-Releasing Hormone
  • Estradiol
  • Norepinephrine