Xing Jinshan, Qiao Gan, Luo Xin, Liu Shuang, Chen Shaokun, Ye Geng, Zhang Chunxiang, Yi Jingyan
Department of Neurosurgery, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China.
Department of Pharmacology, School of Pharmacy, Nucleic Acid Medicine of Luzhou Key Laboratory, Southwest Medical University, Luzhou 646000, Sichuan, China.
Clin Sci (Lond). 2023 Mar 31;137(6):453-468. doi: 10.1042/CS20220408.
Polycystic ovary syndrome (PCOS), a common reproductive endocrine disorder in women of reproductive age, causes anovulatory infertility. Increased apoptosis of granulosa cells has been identified as one of the key factors contributing to abnormal follicular development. Ferredoxin 1 (FDX1) encodes a small ferredoxin that is involved in the reduction in mitochondrial cytochromes and the synthesis of various steroid hormones and has the potential to influence the function of granulosa cells. In the present study, we aimed to determine the relationship between FDX1 and follicular granulosa cell function. To this end, we investigated the difference between FDX1 expression in the granulosa cells of 50 patients with PCOS and that of the controls. Furthermore, we sought to elucidate the role and mechanism of FDX1 in PCOS granulosa cells by establishing a mouse PCOS model with dehydroepiandrosterone and KGN (a steroidogenic human granulosa cell-like tumor cell line). The results indicated significant up-regulation of FDX1 in the granulosa cells after androgen stimulation. Knockdown of FDX1 promoted the proliferation of KGN and inhibited apoptosis. Moreover, FDX1 could regulate autophagy by influencing the autophagy proteins ATG3 and ATG7. Our results demonstrated that FDX1 plays a critical role in female folliculogenesis by mediating apoptosis, autophagy, and proliferation. Therefore, FDX1 may be a potential prognostic factor for female infertility.
多囊卵巢综合征（PCOS）是育龄期女性常见的生殖内分泌紊乱疾病，可导致无排卵性不孕。颗粒细胞凋亡增加已被确定为导致卵泡发育异常的关键因素之一。铁氧化还原蛋白1（FDX1）编码一种小的铁氧化还原蛋白，参与线粒体细胞色素的还原以及各种甾体激素的合成，并有可能影响颗粒细胞的功能。在本研究中，我们旨在确定FDX1与卵泡颗粒细胞功能之间的关系。为此，我们研究了50例PCOS患者颗粒细胞中FDX1表达与对照组之间的差异。此外，我们通过用脱氢表雄酮和KGN（一种产类固醇的人颗粒细胞样肿瘤细胞系）建立小鼠PCOS模型，试图阐明FDX1在PCOS颗粒细胞中的作用和机制。结果表明，雄激素刺激后颗粒细胞中FDX1显著上调。敲低FDX1可促进KGN的增殖并抑制凋亡。此外，FDX1可通过影响自噬蛋白ATG3和ATG7来调节自噬。我们的结果表明，FDX1通过介导凋亡、自噬和增殖在女性卵泡发生中起关键作用。因此，FDX1可能是女性不孕的一个潜在预后因素。
