Role of Nuclear factor erythroid 2-related factor 2 (Nrf2) in female and male fertility

Oxidative stress refers to a condition where there is an imbalance between the production of reactive oxygen species and their removal by antioxidants. While the function of reactive oxygen species as specific second messengers under physiological conditions is necessary, their overproduction can lead to numerous instances of cell and tissue damage. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of many cytoprotective genes that respond to redox stresses. Nrf2 is regularly degraded by kelch-like ECH-associated protein 1 through the ubiquitin-proteasome pathway. The kelch-like ECH-associated protein 1 and Nrf2 complex have attracted attention in both basic and clinical infertility research fields. Oxidative stress is implicated in the pathogenesis of female infertility, including primary ovarian insufficiency, polycystic ovarian syndrome, and endometriosis, as well as male infertility, namely varicocele, cryptorchidism, spermatic cord torsion, and orchitis. Most scientists believe that Nrf2 is a potential therapeutic method in female and male infertility disorders due to its antioxidant effect. Here, the potential roles of oxidative stress and Nrf2 in female and male infertility disorders are reviewed. Moreover, the key role of Nrf2 in the inhibition or induction of these diseases is discussed.