Neonatal and juvenile exposure to perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS): Advance puberty onset and kisspeptin system disturbance in female rats

Ecotoxicol Environ Saf. 2019 Jan 15:167:412-421. doi: 10.1016/j.ecoenv.2018.10.025. Epub 2018 Oct 24.

Abstract

Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are widespread and persistent chemicals in the environment, and limited data about their effects on puberty development are available. In order to explore the effects of neonatal and juvenile PFOA/PFOS exposure on puberty maturation, female rats were injected with PFOA or PFOS at 0.1, 1 and 10 mg/kg/day during postnatal day (PND) 1-5 or 26-30. The day of vaginal opening (VO) and first estrus were significantly advanced in 10 mg/kg PFOA, 1 and 10 mg/kg PFOS groups after neonatal and juvenile exposure. Besides, neonatal PFOA/PFOS exposure increased body weight and anogenital distance (AGD) in a non-dose-dependent manner. Estradiol and luteinizing hormone levels were also increased with more frequent occurrences of irregular estrous cycles in 0.1 and 1 mg/kg PFOA/PFOS exposure groups. Although no altered ovarian morphology was observed, follicles numbers were reduced in neonatal groups. Kiss1, Kiss1r and ERα mRNA expressions were downregulated after two periods' exposure in the hypothalamic anteroventral periventricular (AVPV) and arcuate (ARC) nuclei. PFOA/PFOS exposure also suppressed kisspeptin fiber intensities, especially at the high dose. In conclusion, neonatal and juvenile are critical exposure periods, during which puberty maturation may be vulnerable to environmental exposure of PFOA/PFOS, and kisspeptin system plays a key role during these processes.

Keywords: Hypothalamus; Kisspeptin/GPR54; PFOA; PFOS; Puberty.

MeSH terms

  • Alkanesulfonic Acids / toxicity*
  • Animals
  • Body Weight / drug effects
  • Caprylates / toxicity*
  • Down-Regulation / drug effects
  • Estradiol / blood
  • Estrogen Receptor alpha / genetics
  • Estrous Cycle / drug effects
  • Female
  • Fluorocarbons / toxicity*
  • Hypothalamus / metabolism*
  • Kisspeptins / genetics
  • Kisspeptins / metabolism*
  • Luteinizing Hormone / blood
  • Ovarian Follicle / drug effects
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Kisspeptin-1 / genetics
  • Sexual Maturation / drug effects*

Substances

  • Alkanesulfonic Acids
  • Caprylates
  • Estrogen Receptor alpha
  • Fluorocarbons
  • Kiss1 protein, rat
  • Kiss1r protein, rat
  • Kisspeptins
  • RNA, Messenger
  • Receptors, Kisspeptin-1
  • Estradiol
  • Luteinizing Hormone
  • perfluorooctanoic acid
  • perfluorooctane sulfonic acid