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

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.

Effect of N-acetylcysteine on hair follicle changes in mouse model of cyclophosphamide-induced alopecia: histological and biochemical study

“…In addition, NAC improves mitochondrial function and promotes the nuclear translocation of nuclear factor erythroid 2‐related factor 2 that enhances the expression of the antioxidant enzymes SOD and GSH peroxidase (Fan et al. 2022 ).…”

Efficacy of N-Acetylcysteine on Endometriosis-Related Pain, Size Reduction of Ovarian Endometriomas, and Fertility Outcomes

“…Moreover, the mucolytic and fluidifying effect can improve both the quality of cervical mucus, facilitating the ascent of spermatozoa through the female genital tracts, and the tubal function in patient fallopian tubes [ 32 ], detectable by using the sonohysterosalpingography [ 33 ]. Recently, a study conducted by Fan et al demonstrated how NAC, in vitro, reduces mitochondrial damage in oocytes [ 34 ]. Finally, the reduction of painful symptoms allowed an increased rate of sexual intercourses, with a higher probability of conception.…”

NRF2 in dermo‐cosmetic: From scientific knowledge to skin care products

“…It also possesses direct antioxidative activities thanks to the disulfide bond reduction and ROS scavenging capacity of its thiol group. NAC has been shown to modulate the Nrf2 pathway, either indirectly by ROS quenching‐mediated Nrf2 activity rescue, 165 by increasing Nrf2 expression, 166–168 or more directly by promoting the nuclear translocation of Nrf2 169 . NAC is a cosmetic ingredient (as an AOX and skin conditioner 117 ) and its potential use in dermatology has been recently reviewed, however, no direct link has been made with Nrf2 pathway induction 170 .…”

“…NAC has been shown to modulate the Nrf2 pathway, either indirectly by ROS quenching-mediated Nrf2 activity rescue, 165 by increasing Nrf2 expression, [166][167][168] or more directly by promoting the nuclear translocation of Nrf2. 169 NAC is a cosmetic ingredient (as an AOX and skin conditioner 117 ) and its potential use in dermatology has been recently reviewed, however, no direct link has been made with Nrf2 pathway induction. 170 Indeed, NAC may act via several mechanisms not fully described yet.…”