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

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\u202f=\u202f14; WT) and Ahr knock out (n\u202f=\u202f11; AHR-/-) rats received a single intraperitoneal injection of either corn oil vehicle (5\u202fml/kg: WT_O and AHR-/-_O) or PCB126 (1.63\u202fmg/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\u202fdays after exposure. In WT rats, PCB126 exposure reduced (P\u202f<\u202f0.05) 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\u202f<\u202f0.05). In AHR-/- rats, PCB126 exposure increased (P\u202f≤\u202f0.05) circulating luteinizing hormone level. Ovarian or uterine mRNA abundance of biotransformation, and inflammation genes were altered (P\u202f<\u202f0.05) in WT rats due to PCB126 exposure. In AHR-/- rats, the transcriptional effects of PCB126 were restricted to reductions (P\u202f<\u202f0.05) 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.