From germ cells to neonates: the beginning of life and the KEAP1-NRF2 system

The Kelch-like ECH-associated protein 1(KEAP1)-NF-E2-related factor 2 (NRF2) system is one of the most studied environmental stress response systems. In the presence of oxidative and electrophilic insults, the thiols of cysteine residues in KEAP1 are modified, and subsequently stabilized NRF2 activates its target genes that are involved in detoxification and cytoprotection. A myriad of recent studies has revealed the broad range of contributions of the KEAP1-NRF2 system to physiological and pathological processes. However, its functions during gametic and embryonic development are still open for investigation. Although oxidative stress is harmful for embryos, Nrf2-/- mice do not show any apparent morphological abnormalities during development, probably because of the compensatory antioxidant functions of NF-E2-related factor 1 (NRF1). It can also be considered that the antioxidant system is essential for protecting germ cells during reproduction. The maturation processes of germ cells in both sexes are affected by Nrf2 mutation. Hence, in this review, we focus on the stress response system related to reproduction and embryonic development through the functions of the KEAP1-NRF2 system.