Center for Reproductive Medicine, Dongguan Maternal and Child Health Care Hospital Dongguan, China.
State Key Laboratory of Organ Failure Research; National Clinical Research Center for Kidney Disease; Guangdong Provincial Institute of Nephrology; Guangdong Provincial Key Laboratory of Renal Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Biol Reprod. 2024 Sep 14;111(3):625-639. doi: 10.1093/biolre/ioae094.
The morbidity of polycystic ovary syndrome (PCOS) is in highly increasing rate nowadays. PCOS not only affects the fertility in women, but also threatens the health of whole life. Hence, to find the prognostic risk factors is of great value. However, the effective predictors in clinical practice of PCOS are still in blackness. In this study, we found Klotho (KL) was increased in follicular fluid (FF) and primary luteinized granulosa cells (GCs) from PCOS patients with hyperandrogenism. Furthermore, we found follicular KL was negatively correlated with numbers of mature oocytes, and positively correlated with serum testosterone, LH, and LH/FSH levels menstrual cycle and number of total antral follicles in PCOS patients. In primary luteinized GCs, the increased KL was accompanied with upregulation of cell apoptosis and inflammation-related genes. In ovaries of PCOS mice and cultured human KGN cell line, KL was up-regulated and accompanied by apoptosis, inflammation, and mitochondrial dysfunction. Therefore, our findings suggest new mechanisms for granulosa cell injury and revealed to target inhibit KL maybe a new therapeutic strategy for treatment of PCOS.
多囊卵巢综合征(PCOS)的发病率正在呈高发趋势。PCOS 不仅影响女性的生育能力,还威胁着女性的整体健康。因此,寻找预测疾病预后的风险因素具有重要意义。然而,目前临床上用于预测 PCOS 的有效指标仍不清楚。本研究发现,高雄激素血症 PCOS 患者的卵泡液(FF)和原始黄体化颗粒细胞(GC)中 Klotho(KL)水平升高。此外,我们发现卵泡 KL 与成熟卵母细胞数量呈负相关,与血清睾酮、LH 和 LH/FSH 水平、月经周期和 PCOS 患者总窦卵泡数呈正相关。在原始黄体化的 GC 中,KL 的增加伴随着细胞凋亡和炎症相关基因的上调。在 PCOS 小鼠的卵巢和培养的人 KGN 细胞系中,KL 上调并伴随着细胞凋亡、炎症和线粒体功能障碍。因此,我们的研究结果为颗粒细胞损伤提供了新的机制,并表明抑制 KL 可能是治疗 PCOS 的一种新的治疗策略。