Estradiol protects female mice from hyperuricemia induced by PCB138 exposure

• Published in: Ecotoxicology and environmental safety Vol. 261; p. 115093
• Main Authors: Liu, Changqian, Ruan, Jinpeng, Ruan, Fengkai, Ding, Xiaoyan, Han, Changshun, Huang, Chaoqun, Zhong, Hongbin, He, Chengyong, Zuo, Zhenghong, Huang, Jiyi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.08.2023; Elsevier
• Subjects: 17β-estradiol; Hyperuricemia; Kidney injury; Polychlorinated biphenyls; Sexual dimorphism; Polychlorinated biphenyls; Hyperuricemia; 17β-estradiol; Sexual dimorphism; Kidney injury
• ISSN: 0147-6513; 1090-2414; 1090-2414
• DOI: 10.1016/j.ecoenv.2023.115093

Polychlorinated biphenyls (PCBs) are a type of persistent organic pollutant (POP). Our previous study demonstrated that exposure to 0.5–50 μg/kg bw PCB138 during postnatal days (PND) 3–21 led to elevated serum uric acid (UA) levels and kidney injury in adult male mice. Given that the prevalence of hyperuricemia (HUA) is significantly lower in women than in men, it is worth investigating whether POP-induced HUA and its secondary kidney injury have sexual dimorphism. Herein, we exposed female mice to 0.5–50 μg/kg bw PCB138 during PND 3–21, resulting in elevated serum UA levels, but without causing significant kidney damage. Concurrently, we found a negative correlation between serum 17β-estradiol (E2) and serum UA levels. We also observed down-regulation of estrogen receptor (ER) protein levels in the kidneys of the PCB138-exposed groups. Furthermore, our study showed that E2 rescued the increased UA level and cytotoxicity caused by HUA in human renal tubular epithelial (HK-2) cells. Collectively, our findings suggest that E2 likely plays a crucial protective role in PCB138-induced HUA and kidney injury in female mice. Our research highlights the existence of sexual dimorphism in kidney injury secondary to HUA induced by POPs, which could provide guidance for individuals of different genders in preventing kidney injury caused by environmental factors. [Display omitted] •PCB138 causes hyperuricemia in female mice by inhibiting ABCG2 expression in kidney.•A sexual dimorphism exists in PCB138-induced kidney injury secondary to HUA.•17β-estradiol protects female mice from PCB138-induced kidney injury.