Title: Identifying sex differences arising from polychlorinated biphenyl exposures in toxicant-associated liver disease.
Authors: Wahlang, Banrida; Jin, Jian; Hardesty, Josiah E; Head, Kimberly Z; Shi, Hongxue; Falkner, K Cameron; Prough, Russell A; Klinge, Carolyn M; Cave, Matthew C
Published In Food Chem Toxicol, (2019 Jul)
Abstract: Exposures to persistent environmental pollutants like polychlorinated biphenyls (PCBs) has been associated with liver diseases such as toxicant-associated steatohepatitis (TASH). However, previously published PCB hepatotoxicity studies evaluated mostly male animal models. Moreover, epidemiologic studies on PCB-exposed cohorts evaluating sex differences are scarce. Therefore, the objective of this study was to examine hepato-toxicological responses of PCB exposures in the context of sex-dependent outcomes. Male and female C57Bl/6 mice were exposed to Aroclor 1260 (20 mg/kg), and PCB126 (20 μg/kg), by gavage for two weeks. Female mice appeared to be more sensitive to PCB-induced hepatotoxic effects as manifested by increased liver injury markers, namely, hepatic Serpine1 expression. Additionally, compared to their male counterparts, PCB-exposed females exhibited dysregulated hepatic gene expression favoring lipid accumulation rather than lipid breakdown; accompanied by dyslipidemia. Sex differences were also observed in the expression and activation of PCB targets such as the epidermal growth factor receptor (EGFR) while PCB-induced pancreatic toxicity was similar in both sexes. Importantly, PCB exposure appeared to cause pro-androgenic, anti-estrogenic along with sex-dependent thyroid hormone effects. The overall findings demonstrated that the observed PCB-mediated hepatotoxicity was sex-dependent; confirming the existence of sex differences in environmental exposure-induced markers of TASH and warrants further investigation.
PubMed ID: 31026535
MeSH Terms: Adipokines/blood; Animals; Aroclors/toxicity*; Body Weight/drug effects; Chemical and Drug Induced Liver Injury/etiology*; Cytokines/blood; Endocrine Disruptors/toxicity*; Female; Glucose/metabolism; Lipids/blood; Liver/drug effects; Liver/metabolism; Male; Mice; Mice, Inbred C57BL; Organ Size/drug effects; Polychlorinated Biphenyls/toxicity*; Sex Factors*