The Aryl hydrocarbon receptor mediates reproductive toxicity of polychlorinated biphenyl congener 126 in rats

Toxicol Appl Pharmacol. 2021 Sep 1;426:115639. doi: 10.1016/j.taap.2021.115639. Epub 2021 Jul 10.

Abstract

Polychlorinated biphenyls (PCBs) are endocrine disrupting chemicals with documented, though mechanistically ill-defined, reproductive toxicity. The toxicity of dioxin-like PCBs, such as PCB126, is mediated via the aryl hydrocarbon receptor (AHR) in non-ovarian tissues. The goal of this study was to examine the uterine and ovarian effects of PCB126 and test the hypothesis that the AHR is required for PCB126-induced reproductive toxicity. Female Holzman-Sprague Dawley wild type (n = 14; WT) and Ahr knock out (n = 11; AHR-/-) rats received a single intraperitoneal injection of either corn oil vehicle (5 ml/kg: WT_O and AHR-/-_O) or PCB126 (1.63 mg/kg in corn oil: WT_PCB and AHR-/-_PCB) at four weeks of age. The estrous cycle was synchronized and ovary and uterus were collected 28 days after exposure. In WT rats, PCB126 exposure reduced (P < 0.05) body and ovary weight, uterine gland number, uterine area, progesterone, 17β-estradiol and anti-Müllerian hormone level, secondary and antral follicle and corpora lutea number but follicle stimulating hormone level increased (P < 0.05). In AHR-/- rats, PCB126 exposure increased (P ≤ 0.05) circulating luteinizing hormone level. Ovarian or uterine mRNA abundance of biotransformation, and inflammation genes were altered (P < 0.05) in WT rats due to PCB126 exposure. In AHR-/- rats, the transcriptional effects of PCB126 were restricted to reductions (P < 0.05) in three inflammatory genes. These findings support a functional role for AHR in the female reproductive tract, illustrate AHR's requirement in PCB126-induced reprotoxicity, and highlight the potential risk of dioxin-like compounds on female reproduction.

Keywords: Aryl hydrocarbon receptor; Aryl hydrocarbon receptor knock out; PCB126; Polychlorinated biphenyl; Reproductive toxicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / deficiency*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Biotransformation / genetics
  • Body Weight / drug effects
  • Endocrine Disruptors / toxicity*
  • Female
  • Gene Expression Regulation / drug effects
  • Hormones / blood
  • Organ Size / drug effects
  • Ovary / drug effects
  • Ovary / metabolism
  • Ovary / pathology
  • Polychlorinated Biphenyls / toxicity*
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Rats, Transgenic
  • Receptors, Aryl Hydrocarbon / deficiency*
  • Receptors, Aryl Hydrocarbon / genetics
  • Reproduction / drug effects
  • Uterus / drug effects
  • Uterus / metabolism
  • Uterus / pathology

Substances

  • Ahr protein, rat
  • Basic Helix-Loop-Helix Transcription Factors
  • Endocrine Disruptors
  • Hormones
  • RNA, Messenger
  • Receptors, Aryl Hydrocarbon
  • Polychlorinated Biphenyls
  • 3,4,5,3',4'-pentachlorobiphenyl