N-Acetylcysteine improves oocyte quality through modulating the Nrf2 signaling pathway to ameliorate oxidative stress caused by repeated controlled ovarian hyperstimulation

Fan L, Lijie Fan, Fengli Guan, Guan F, Ma Y, Yucong Ma, Zhang Y, Yu Zhang, Li L, Li Li, Sun Y, Ying Sun, Can Cao, Cao C, Huilan Du, Du H, He M, Ming He
Reproduction, fertility, and development · 2022 · vol. 34(10) , pp. 736–750 · doi:10.1071/rd22020 · PMID:35513370 · W4229015551
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N-acetylcysteine ameliorates oxidative stress and improves oocyte mitochondrial function in mice undergoing repeated controlled ovarian hyperstimulation by activating the Nrf2 signaling pathway.

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Abstract

CONTEXT: N -acetyl-cysteine (NAC) is a potent antioxidant that can be used for many gynecological diseases such as polycystic ovary syndrome and endometriosis. Controlled ovarian hyperstimulation (COH) is a critical step in infertility treatment. Our previous clinical studies have shown that repeated COH led to oxidative stress in follicle fluid and ovarian granulosa cells. AIMS: In this study, we investigated whether NAC could inhibit oxidative stress in mice caused by repeated COH and improve the mitochondrial function of oocytes. METHODS: Female Institute of Cancer Research (ICR) mice were randomly assigned into three groups: normal group, model (repeated COH) group, NAC group. We examined the morphology, number and quality of mitochondria. The mechanism of regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) by NAC to ameliorate oxidative stress was also investigated. KEY RESULTS: Repeated COH caused oxidative damage in ovaries and oocytes and decreased oocyte quality, while NAC prevented oxidative damage and increased oocyte mitochondrial function. In in vitro experiments, it was verified that NAC can promote the nuclear translocation of Nrf2, which transcriptionally activates the expression of superoxide dismutase and glutathione peroxidase, which removed excessive reactive oxygen species that causes mitochondria damage. CONCLUSIONS: The results suggest that NAC raises mitochondrial function in oocytes and improves oocyte quality through decreasing oxidative stress in mice with repeated COH. The underlying mechanism is related to the regulation of the Nrf2 signaling pathway. IMPLICATION: This study provides a meaningful foundation for the future clinical application of NAC during repeated COH.

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Condition tags

endometriosisinfertility

MeSH descriptors

Acetylcysteine Acetylcysteine Acetylcysteine Acetylcysteine Acetylcysteine Acetylcysteine Acetylcysteine Acetylcysteine Acetylcysteine Acetylcysteine Acetylcysteine Acetylcysteine Acetylcysteine Acetylcysteine Acetylcysteine Acetylcysteine Acetylcysteine Acetylcysteine Acetylcysteine Acetylcysteine

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