Role of the Nrf2 Signaling Pathway in Ovarian Aging: Potential Mechanism and Protective Strategies

Abstract

The ovary holds a significant role as a reproductive endocrine organ in women, and its aging process bears implications such as menopause, decreased fertility, and long-term health risks including osteoporosis, cardiovascular disorders, and cognitive decline. The phenomenon of oxidative stress is tightly linked to the aging metabolic processes. More and more studies have demonstrated that oxidative stress impacts both physiologic and pathologic ovarian aging, and the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a crucial role in regulating the antioxidant response. Furthermore, various therapeutic approaches have been identified to ameliorate ovarian aging by modulating the Nrf2 pathway. This review summarizes the important role of the Nrf2/ Kelch-like ECH-associated protein 1 (Keap1) signaling pathway in regulating oxidative stress and influencing ovarian aging. Additionally, it highlights the therapeutic strategies aimed at targeting the Nrf2/Keap1 pathway.

Molecular Mechanism of Resveratrol and Its Therapeutic Potential on Female Infertility

“…Resveratrol also decreased the number of atretic follicles in the fish ovaries. It also increased the expression of SIRT1 and nuclear factor erythroid 2-related factor 2 (NRF2) [126], a regulator of oxidative stress and antioxidant response, promoting the expression of antioxidant enzymes, therefore protecting against ovarian aging [129]. Upon resveratrol supplementation, a reduction of inflammatory markers IL-1β, TNF-α, and IL-8, including the NF-κB transcription factor involved with the induction of cytokine expression [130], was observed [126].…”

Role of SLC7A11/xCT in Ovarian Cancer

“…In fact, the depletion of ovarian function during aging not only leads to a reduced reproductive capacity but also increases the risk of ovarian cancer. This cancer can therefore be considered an aging-related disease [ 4 ].…”