Estradiol protects female mice from hyperuricemia induced by PCB138 exposure

Polychlorinated biphenyls (PCBs) are a type of persistent organic pollutant (POP). Our previous study demonstrated that exposure to 0.5-50 mu g/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 mu g/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 17 beta-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.