Preventive Role of Simvastatin against Infertility: Potential Role of PGC-a/PPARβ/UCPs and NF-κβ Signaling Pathways

Several inflammatory-related signaling pathways are involved in infertility. A common feature involves activating inflammatory cascades in the mitochondrial respiratory chain. Oxidative stress triggers mitochondrial dysfunction and initiates intrinsic apoptosis pathways, leading to cell damage/death in germ cells. Disruption of the mitochondrial respiratory chain is a leading cause of degenerative disorders of germ cells. However, the signaling pathways responsible for disrupting the mitochondrial respiratory chain function are unclear and require further studies. Among the signaling pathways potentially involved, the PGC-α/PPARβ/UCPs pathway has been reported to modulate mitochondrial function in germ cells. Although the role of the cell death cascades on germ cell-induced damage has not been unwoven, apoptosis, necrosis, autophagy, and their related signaling cascades play roles in infertility. Thus, therapeutic agents, such as simvastatin, with anti-cell death properties should be considered as possible new therapeutic approaches for managing infertility.