Neonatal exposure to 17α-ethynyl estradiol (EE) disrupts follicle development and reproductive hormone profiles in female rats

Toxicol Lett. 2017 Jul 5:276:92-99. doi: 10.1016/j.toxlet.2017.05.014. Epub 2017 May 15.

Abstract

Toxic effects induced by exposure to endocrine-disrupting chemicals during fetal and neonatal periods can be irreversible and exert effects throughout an animal's entire life. Our previous study showed that neonatal exposure to 17α-ethynyl estradiol (EE) induced irregular estrous cycle in adults. To uncover the reason for the delayed effect after neonatal exposure to EE, reproductive parameters including ovarian weight, ovarian steroidogenesis, and hormonal profiles were investigated in developing female rats. Ovarian weight decreased at postnatal days (PND) 14 and 21 after neonatal exposure to EE. Ovarian histology at PND21 showed that the ratio of follicles with a diameter >300μm decreased and the ratio of follicles with a diameter of 100-150μm increased in EE-treated ovaries, indicating that neonatal exposure to EE retarded follicular development. Moreover, the expression of P450arom increased at PND14 and the expressions of inhibin/activin subunits βA and βB decreased at PND21 in EE-treated ovaries. Consistent with the expression of P450arom, circulating levels of 17β-estradiol increased at PND14 in EE-treated animals. Furthermore, the circulating levels of luteinizing hormone (LH) also increased at PND14 in the treated animals. Although the expression of Kiss1 did not change in the anteroventral periventricular nucleus (AVPV) of the hypothalamus between controls and EE-treated rats, the expression of Kiss1 was reduced in the arcuate nucleus (ARC) of the hypothalamus at PND14. Based upon those results, we suggest that neonatal exposure to EE disrupted the system regulating the interactions between the reproductive hormones and follicle development in pre-pubertal rats, which may result in reproduction dysfunction in adulthood.

Keywords: 17α-ethynyl estradiol (EE); Endocrine-disrupting chemicals; Inhibins/activins; Ovary; Steroid hormones.

MeSH terms

  • Animals
  • Animals, Newborn
  • Arcuate Nucleus of Hypothalamus / drug effects
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Aromatase / genetics
  • Aromatase / metabolism
  • Cell Proliferation / drug effects
  • Endocrine Disruptors / toxicity*
  • Estradiol / blood
  • Ethinyl Estradiol / toxicity*
  • Female
  • Gonadal Hormones / blood
  • Gonadal Hormones / metabolism*
  • Inhibin-beta Subunits / metabolism
  • Kisspeptins / genetics
  • Kisspeptins / metabolism
  • Luteinizing Hormone / blood
  • Organ Size / drug effects
  • Ovarian Follicle / drug effects*
  • Ovarian Follicle / metabolism
  • Ovarian Follicle / pathology
  • Ovary / drug effects*
  • Ovary / metabolism
  • Ovary / pathology
  • Rats, Wistar
  • Reproduction / drug effects*

Substances

  • Endocrine Disruptors
  • Gonadal Hormones
  • Kiss1 protein, rat
  • Kisspeptins
  • inhibin beta A subunit
  • Ethinyl Estradiol
  • Estradiol
  • Luteinizing Hormone
  • Inhibin-beta Subunits
  • Aromatase