Oxidative stress-induced apoptosis and autophagy: Balancing the contrary forces in spermatogenesis

Spermatogenesis is a complex process in the testis and is a cornerstone of male infertility. The abundance of unsaturated fatty acid and high cell division rate make male germs cells prone to DNA deterioration. ROS-mediated oxidative stress triggers DNA damage, autophagy, and apoptosis in male germ cells, which are critical causative factors that lead to male infertility. The complex connection and molecular crosstalk between apoptosis and autophagy is seen at multifaceted levels that interconnect the signaling pathways of these two processes. Multilevel interaction between apoptosis and autophagy is a seamless state of survival and death in response to various stressors. Interaction between multiple genes and proteins such as the mTor signaling pathway, Atg12 proteins, and the death adapter proteins, such as Beclin 1, p53, and Bcl-2 family proteins, validates such a link between these two phenomena. Testicular cells being epigenetically different from somatic cells, undergo numerous significant epigenetic transitions, and ROS modulates the epigenetic framework of mature sperm. Epigenetic deregulation of apoptosis and autophagy under oxidative stress conditions can cause sperm cell damage. The current review recapitulates the current role of prevailing stressors that generate oxidative stress leading to the induction of apoptosis and autophagy in the male reproductive system. Considering the pathophysiological consequences of ROS-mediated apoptosis and autophagy, a combinatorial approach, including apoptosis inhibition and autophagy activation, should be implemented as a therapeutic strategy to treat male idiopathic infertility. Understanding the crosslink between apoptosis and autophagy under stress conditions in male germ cells may play an essential role in developing therapeutic strategies to treat infertility. •Review on oxidative stress induced autophagy and apoptosis leading to male infertility.•Role of apoptosis and autophagy in the maintenance and preservation of spermatogenesis•Oxidative stress induced epigenetic mechanisms to regulate spermatogenesis.•Effect of ROS in the crosstalk between apoptosis and autophagy during impaired spermatogenesis•Antioxidant and stem cell mediated therapeutic methods to treat ROS-mediated male infertility.