Lead-induced apoptosis in Sertoli cells is associated with Ca²⁺ dysregulation

Lead (Pb) is a common environmental toxicant associated with male reproductive injury. Sertoli cells (SCs) are essential for spermatogenesis, but the mechanism of Pb-induced SC injury remains unclear. This study investigated whether Pb exposure induces SC apoptosis and explored the possible mechanisms involved.

An early pubertal mouse model of Pb exposure and TM4 cells were used. Cell viability, morphology, apoptosis, apoptosis-related protein expression, intracellular Ca²⁺ levels, membrane potential-related fluorescence, and ERK phosphorylation were assessed. Nifedipine, Bay K8644, and U0126 were used for intervention.

Pb exposure induced a pro-apoptotic molecular expression pattern in mouse testes. In TM4 cells, Pb reduced cell viability, induced morphological deterioration, and increased apoptosis in a concentration- and time-dependent manner. Pb also altered intracellular Ca²⁺ levels and membrane potential-related fluorescence. Nifedipine partially reversed Pb-induced changes in Bax and Bcl-2, whereas Bay K8644 produced no additional significant effect. Pb reduced the p-ERK1/2-to-total ERK1/2 ratio, and U0126 further suppressed ERK phosphorylation and aggravated apoptosis-related molecular alterations.

Pb exposure induced apoptosis-related molecular alterations in mouse testes and apoptosis in TM4 SCs. These effects were associated with disrupted Ca²⁺ homeostasis, and inhibition of ERK signaling further aggravated Pb-induced apoptosis-related molecular alterations.