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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

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

Authors: Klenov, Violet; Flor, Susanne; Ganesan, Shanthi; Adur, Malavika; Eti, Nazmin; Iqbal, Khursheed; Soares, Michael J; Ludewig, Gabriele; Ross, Jason W; Robertson, Larry W; Keating, Aileen F

Published In Toxicol Appl Pharmacol, (2021 09 01)

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.

PubMed ID: 34256052 Exiting the NIEHS site

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

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