Sodium pentachlorophenol induces inflammatory damage via the ATP2B4/Ca²⁺/ROS signaling axis in mouse testes

Sodium pentachlorophenol (PCP-Na) is widely used in agricultural production and daily life as an insecticide, herbicide, and molluscicide, and it is stable and difficult to biodegrade in soil after application. The mechanism by which it causes testicular damage remains unclear. Our results indicated that PCP-Na causes decreased expression of the calcium ion transporter ATP2B4 (Plasma membrane calcium-transporting ATPase 4), reduced testosterone levels, and elevated calcium ion levels, oxidative stress, and inflammation. Decreased ATP2B4 expression was positively correlated with testosterone levels and negatively correlated with ROS (Reactive oxygen species) and calcium ion levels, with significant correlations observed among all four factors. Following treatment with NAC and BAPTA-AM inhibitors in vitro experiments, both results indicated that PCP-Na reduces ATP2B4 protein expression by acting on the ATP2B4 protein. This prevents intracellular calcium ions from being transported out of the cell normally, causing them to accumulate and leading to calcium overload. Calcium overload further induces oxidative stress reactions. In vitro experiments involving ATP2B4 protein siRNA transfection demonstrated that ATP2B4 protein serves as a key upstream protein in this study. Collectively, our results demonstrate that the ATP2B4/Ca²⁺/ROS signaling axis drives PCP-Na-induced inflammatory damage in mouse testes.