Humanin regulates oxidative stress in the ovaries of polycystic ovary syndrome patients via the Keap1/Nrf2 pathway
Humanin regulates oxidative stress in the ovaries of polycystic ovary syndrome patients via the Keap1/Nrf2 pathway
复制标题
护脑素通过 Keap1/Nrf2 通路调节多囊卵巢综合征患者卵巢的氧化应激。
DOI：
10.1093/molehr/gaaa081
复制
发表时间：
2021-02-01
影响因子：
4
通讯作者：
Rao, Meng
中科院分区：
文献类型：
--
作者：
Wang, Yingying;Li, Nianyu;Rao, Meng
多囊卵巢综合征（PCOS）是育龄妇女中最常见的内分泌疾病，其发病机制尚未完全清楚。全身和卵巢氧化应激（OS）失衡是PCOS的关键特征。Humanin是一种线粒体衍生的肽，据报道在心肌细胞、胰腺β细胞和其他细胞中起抗氧化剂的作用，但这种功能如何调节仍不清楚。在这项研究中，我们调查了多囊卵巢综合征患者与对照组颗粒细胞中人素表达是否不同，以及人素是否加重了多囊卵巢综合征卵巢的氧化应激。16例PCOS患者和28例年龄和BMI匹配的对照接受IVF，并收集他们的血清，卵泡液和颗粒细胞进行人胰岛素分析。采用脱氢表雄酮诱导的大鼠PCOS模型和维生素K3（vitK 3）诱导的COV 434细胞株OS，探讨其作用机制。与非PCOS患者相比，PCOS患者卵巢中Humanin表达显著下调。补充外源性humanin可显著减轻PCOS大鼠模型的体重增加、卵巢形态学异常、内分泌紊乱以及卵巢和全身OS。我们的研究进一步表明，这种衰减效应参与了Keap 1/Nrf 2信号通路的调节。总之，这项研究首次报道了颗粒细胞中人素表达的减少与PCOS中的氧化失衡有关。Humanin通过调节Keap 1/Nrf 2信号通路减轻PCOS患者卵巢颗粒细胞的氧化应激
Polycystic ovary syndrome (PCOS) is the most common endocrinological pathology among women of reproductive age, whereas the pathogenesis is still not fully understood. Systemic and ovarian oxidative stress (OS) imbalance is a pivotal feature of PCOS. Humanin, a mitochondria derived peptide, has been reported to function as an antioxidant in cardiomyocytes, pancreatic beta cells, and other cells, but how this function is regulated remains unclear. In this study, we investigated whether humanin expression differs in the granulosa cells of PCOS patients versus controls, and whether humanin alleviates oxidative stress in PCOS ovaries. Sixteen PCOS patients and twenty-eight age and BMI-matched controls undergoing IVF were recruited, and their serum, follicular fluid and granulosa cells were collected for humanin analysis. Dehydroepiandrosterone-induced rat PCOS models, and vitamin K3 (vitK3)-induced OS COV434 cell lines were to investigate the mechanism. Humanin expression was significantly down-regulated in the ovaries of PCOS patients relative to those of non-PCOS patients. Exogenous humanin supplementation significantly attenuated body weight gain, ovarian morphological abnormalities, endocrinological disorders and ovarian and systemic OS in PCOS rat models. Our study further demonstrated that this attenuation effect was involved in the modulation of the Keap1/Nrf2 signalling pathway. In summary, this study reported for the first time that decreased expression of humanin in the granulosa cells was associated with oxidative imbalance in PCOS. Humanin alleviates oxidative stress in ovarian granulosa cells of PCOS patients via modulation of the Keap1/Nrf2 signaling pathway.