Identifying sex differences arising from polychlorinated biphenyl exposures in toxicant-associated liver disease. (July 2019)

• Record Type: Journal Article
• 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.
• Is Part Of: Food and chemical toxicology. Volume 129(2019)
• Page Start: 64
• Page End: 76
• Publication Date: 2019-07
• Subjects: PCBs -- Sex differences -- Metabolic -- Endocrine -- TASH; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2019.04.007
• Languages: English
• ISSNs: 0278-6915

Abstract

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. Highlights: Male and female mice were exposed to a mixture of polychlorinated biphenyls (PCBs). PCB exposure resulted in disruption of hepatic metabolism in both sexes. PCBs caused sex-dependent endocrine disruption. Exposed female mice demonstrated liver injury and pronounced alterations in energy metabolism.