Autophagy Induced by ROS Aggravates Testis Oxidative Damage in Diabetes via Breaking the Feedforward Loop Linking p62 and Nrf2

Figure 1

Mechanistic illustrations. The increasing formation of ROS in DM can directly cause damage to spermatogenesis via attacking the fluidity of the plasma membrane lipids, protein modifications, and integrity of DNA. And ROS also can induce autophagy by inhibiting mTOR through the PI3K/Akt signaling pathway. Autophagy accelerates the degradation of p62, and then, the Nrf2 activation is suppressed and the oxidative damage is aggravated. Autophagy also directly causes damage to spermatogenesis via reducing serum testosterone levels, suppressing SC proliferation, and damaging BTB. Moreover, mTOR has distinct effects on spermatogenesis via promoting spermatogonia proliferation, maintaining somatic cell function, and restructuring BTB. As a result, the oxidative damage in diabetic testes is further enhanced, thereby promoting the occurrence of infertility.