Abstract
sodium pentachlorophenol (PCP-Na) is one of the persistent organic pollutants (POPs) with high lipophilicity. chlorinated hydrocarbon that exhibits broad-spectrum systemic toxicity, accompanied by severe carcinogenic, teratogenic, and mutagenic risks; however, the molecular basis of its gender-specific pathogenesis remains unclear. In this study, mice were exposed to PCP-Na by intraperitoneal injection for 10 days (2.5, 5, and 10 mg/kg). To elucidate the gender-sensitive endocrine mechanism, we evaluated the expression of AR and ERα in the liver and conducted targeted hormone receptor intervention. The results showed that female mice exhibited significantly enhanced sensitivity to PCP-Na, manifested as early growth retardation, elevated AST activity, and exacerbated hepatocyte apoptosis. From a mechanistic perspective, PCP-Na significantly downregulated ERα expression and abnormally upregulated AR, thereby disrupting the microenvironment of the female liver. Crucially, by inhibiting the AR signaling pathway in males and activating ERα in females, the liver damage caused by PCP-Na was successfully alleviated. These findings indicate that due to the specific damage to the natural steroid hormone receptor network by this toxic substance, female mammals are particularly sensitive to PCP-Na. Ultimately, this study provides a mechanistic basis for the use of precise and gender-stratified drug treatment in clinical treatment of environmental toxins.