一氧化氮与氧化应激在典型排卵正常女性及 PCOS 排卵障碍发病机制中的研究进展。
A review of nitric oxide and oxidative stress in typical ovulatory women and in the pathogenesis of ovulatory dysfunction in PCOS.
机构信息
Departments of Obstetrics and Gynecology and Biochemistry and Molecular Biology, The C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, 275 E. Hancock Detroit, Detroit, MI, 48201, USA.
Department of Physiology, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
出版信息
Reprod Biol Endocrinol. 2023 Nov 23;21(1):111. doi: 10.1186/s12958-023-01159-6.
Polycystic ovary syndrome (PCOS) is a heterogeneous functional endocrine disorder associated with a low-grade, chronic inflammatory state. Patients with PCOS present an increased risk of metabolic comorbidities and often menstrual dysregulation and infertility due to anovulation and/or poor oocyte quality. Multiple mechanisms including oxidative stress and low-grade inflammation are believed to be responsible for oocyte deterioration; however, the influence of nitric oxide (NO) insufficiency in oocyte quality and ovulatory dysfunction in PCOS is still a matter for debate. Higher production of superoxide (O) mediated DNA damage and impaired antioxidant defense have been implicated as contributory factors for the development of PCOS, with reported alteration in superoxide dismutase (SOD) function, an imbalanced zinc/copper ratio, and increased catalase activity. These events may result in decreased hydrogen peroxide (HO) accumulation with increased lipid peroxidation events. A decrease in NO, potentially due to increased activity of NO synthase (NOS) inhibitors such as asymmetric dimethylarginine (ADMA), and imbalance in the distribution of reactive oxygen species (ROS), such as decreased HO and increased O, may offset the physiological processes surrounding follicular development, oocyte maturation, and ovulation contributing to the reproductive dysfunction in patients with PCOS. Thus, this proposal aims to evaluate the specific roles of NO, oxidative stress, ROS, and enzymatic and nonenzymatic elements in the pathogenesis of PCOS ovarian dysfunction, including oligo- anovulation and oocyte quality, with the intent to inspire better application of therapeutic options. The authors believe more consideration into the specific roles of oxidative stress, ROS, and enzymatic and nonenzymatic elements may allow for a more thorough understanding of PCOS. Future efforts elaborating on the role of NO in the preoptic nucleus to determine its influence on GnRH firing and follicle-stimulating hormone/Luteinizing hormone (FSH/LH) production with ovulation would be of benefit in PCOS. Consequently, treatment with an ADMA inhibitor or NO donor may prove beneficial to PCOS patients experiencing reproductive dysfunction and infertility.
多囊卵巢综合征(PCOS)是一种异质性的功能性内分泌紊乱,与低度、慢性炎症状态有关。PCOS 患者由于排卵障碍和/或卵子质量差而导致月经失调和不孕的风险增加。多种机制,包括氧化应激和低度炎症,被认为与卵子退化有关;然而,NO 不足对卵子质量和 PCOS 排卵功能障碍的影响仍存在争议。超氧化物(O)介导的 DNA 损伤和抗氧化防御受损的较高产生被认为是 PCOS 发展的促成因素,据报道,超氧化物歧化酶(SOD)功能改变、锌/铜比例失衡和过氧化氢酶活性增加。这些事件可能导致过氧化氢(HO)积累减少和脂质过氧化事件增加。NO 的减少,可能是由于一氧化氮合酶(NOS)抑制剂如不对称二甲基精氨酸(ADMA)的活性增加,以及活性氧(ROS)的分布失衡,如 HO 减少和 O 增加,可能会抵消围绕卵泡发育、卵子成熟和排卵的生理过程,导致 PCOS 患者的生殖功能障碍。因此,本研究旨在评估 NO、氧化应激、ROS 以及酶和非酶元素在 PCOS 卵巢功能障碍发病机制中的特定作用,包括少卵泡排卵和卵子质量,以期为治疗方案的应用提供更好的依据。作者认为,更多地考虑氧化应激、ROS 以及酶和非酶元素的特定作用可能会更全面地了解 PCOS。未来的研究阐述 NO 在视前核中的作用,以确定其对 GnRH 放电和卵泡刺激素/黄体生成素(FSH/LH)产生和排卵的影响,这将对 PCOS 有益。因此,用 ADMA 抑制剂或 NO 供体治疗可能对患有生殖功能障碍和不孕的 PCOS 患者有益。