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Review
. 2022 Sep 1;15(1):100.
doi: 10.1186/s13048-022-01032-x.

The role of oxidative stress in ovarian aging: a review

Fei Yan #  1 , Qi Zhao #  1 , Ying Li #  1 , Zhibo Zheng  1 , Xinliang Kong  1 , Chang Shu  1 , Yanfeng Liu  2 , Yun Shi  3
Affiliations
Review

The role of oxidative stress in ovarian aging: a review

Fei Yan et al. J Ovarian Res. .

Abstract

Ovarian aging refers to the process by which ovarian function declines until eventual failure. The pathogenesis of ovarian aging is complex and diverse; oxidative stress (OS) is considered to be a key factor. This review focuses on the fact that OS status accelerates the ovarian aging process by promoting apoptosis, inflammation, mitochondrial damage, telomere shortening and biomacromolecular damage. Current evidence suggests that aging, smoking, high-sugar diets, pressure, superovulation, chemotherapeutic agents and industrial pollutants can be factors that accelerate ovarian aging by exacerbating OS status. In addition, we review the role of nuclear factor E2-related factor 2 (Nrf2), Sirtuin (Sirt), mitogen-activated protein kinase (MAPK), protein kinase B (AKT), Forkhead box O (FoxO) and Klotho signaling pathways during the process of ovarian aging. We also explore the role of antioxidant therapies such as melatonin, vitamins, stem cell therapies, antioxidant monomers and Traditional Chinese Medicine (TCM), and investigate the roles of these supplements with respect to the reduction of OS and the improvement of ovarian function. This review provides a rationale for antioxidant therapy to improve ovarian aging.

Keywords: Antioxidant; Apoptosis; Cigarette smoking; Inflammation; Melatonin; Nuclear factor E2-related factor 2; Ovarian aging; Oxidative stress; Vitamin C.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Intracellular OS damage
Fig. 2
Fig. 2
OS injury in the ovary. A OS damage of blood vessels, interstitium, follicles and corpus luteum in the ovary. B OS damage of oocytes, granulosa cell, ovarian interstitial cell and follicular fluid in ovarian follicles
Fig. 3
Fig. 3
OS-related signaling pathways in ovarian aging. Excess levels of ROS promote the dissociation of the Keap1-Nrf2 complex and Nrf2 translocation into the nucleus to bind to AREs, thus promoting the expression of antioxidant enzymes. Sirt can deacetylate key proteins involved in the cellular stress response such as FoxO, and regulate both telomerase activity and mitochondrial function through PGC1α. The MAPK cascade signaling pathway is activated by ROS to deliver extracellular signals to the nucleus, promote apoptosis, inhibit proliferation and induce cell cycle arrest. AKT plays an important role in the regulation of cellular redox homeostasis, and phosphorylated AKT can regulate a variety of downstream proteins (Bad, mTOR, Cyclins and Nrf2) to further regulate cellular apoptosis, autophagy and proliferation. FoxO senses cellular OS status and acts as a transcription factor to regulate cell apoptosis and the expression of antioxidant enzymes. Klotho regulates cellular oxidative homeostasis through the PI3K/AKT pathway, and the HPO axis through the FGF-Klotho endocrine system
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