Protective Effects of PGC-1α Against Lead-Induced Oxidative Stress and Energy Metabolism Dysfunction in Testis...

The reproductive system is sensitive to lead (Pb) toxicity, which has long been an area of research interest, but the underlying mechanisms remain to be illustrated. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is pivotal in mitochondrial function. In this study, mouse testis Sertoli cells (TM4 cells), PGC-1α lower-expression (PGC-1α(-)) TM4 cells and PGC-1α overexpression (PGC-1α(+)) TM4 cells were used to explore the protective roles of PGC-1α against lead toxicity on the mouse reproductive system. Lead acetate (PbAc) exposure decreased the expression level of PGC-1α, increased the intracellular level of reactive oxygen species (ROS), and reduced the level of ATP in the three TM4 cell lines. The effects of PbAc on intracellular ATP level and on ROS content were significantly weakened in PGC-1α(+)TM4 cells versus TM4 cells and were significantly amplified in PGC-1α(-)TM4 cells versus TM4 cells. These results suggest that PGC-1α is a protective factor against PbAc-induced oxidative stress and energy metabolism dysfunction in the mouse reproductive system, thereby holding the potential of being developed as a preventive or therapeutic strategy against disorders induced by lead exposure.