Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, No. 111 Yi Xue Yuan Road, Shanghai, 200032, People's Republic of China.
Reproductive Medicine Center, Zhongshan Hospital, Fudan University, No. 250 Xiao Mu Qiao Road, Shanghai, 200032, People's Republic of China.
J Assist Reprod Genet. 2024 May;41(5):1387-1401. doi: 10.1007/s10815-024-03092-y. Epub 2024 Apr 24.
OBJECTIVE: Women who are of reproductive age can suffer from polycystic ovary syndrome (PCOS), an endocrine disorder. Anovulatory infertility is mostly caused by aberrant follicular development, which is seen in PCOS patients. Due to the dysfunction of reproductive and endocrine function in PCOS patients, assisted reproduction treatment is one of the main means to obtain clinical pregnancy for PCOS patients. Long non-coding RNA (lncRNA) as a group of functional RNA molecules have been found to participate in the regulation of oocyte function, hormone metabolism, and proliferation and apoptosis of granulosa cells. In this study, we investigated the role of lncRNAs in follicular fluid-derived exosomes and the underlying mechanism of lncRNA LIPE-AS1. METHODS: We used RNA sequencing to analyze the lncRNA profiles of follicular fluid-derived exosomes in PCOS patients and controls. RT-qPCR was performed to detect the expression levels of these lncRNAs in control (n = 30) and PCOS (n = 30) FF exosome samples. Furthermore, we validated the performance of lncRNA LIPE-AS1 in oocyte maturation by in vitro maturation (IVM) experiments in mouse and steroid metabolism in granulosa cells. RESULTS: We found 501 lncRNAs were exclusively expressed in the control group and another 273 lncRNAs were found to be specifically expressed in the PCOS group. LncRNA LIPE-AS1, highly expressed in PCOS exosomes, was related to a poor oocyte maturation and embryo development in PCOS patients. Reduced number of MII oocytes were observed in the LIPE-AS1 group by in vitro maturation (IVM) experiments in mouse. LIPE-AS1 was also shown to modulate steroid metabolism and granulosa cell proliferation and apoptosis by LIPE-AS1/miR-4306/LHCGR axis. CONCLUSION: These findings suggested that the increased expression of LIPE-AS1, facilitated by follicular fluid exosomes, had a significant impact on both oocyte maturation and embryo development. We demonstrated the ceRNA mechanism involving LIPE-AS1, miR-4306, and LHCGR as a regulator of hormone production and metabolism. These findings indicate that LIPE-AS1 is essential in PCOS oocyte maturation and revealed a ceRNA network of LIPE-AS1 and provided new information on abnormal steroid metabolism and oocyte development in PCOS.
目的：处于生育期的女性可能会患上多囊卵巢综合征（PCOS），这是一种内分泌紊乱疾病。无排卵性不孕主要是由异常的卵泡发育引起的，而这在 PCOS 患者中很常见。由于 PCOS 患者的生殖和内分泌功能障碍，辅助生殖治疗是 PCOS 患者获得临床妊娠的主要手段之一。长链非编码 RNA（lncRNA）作为一组功能 RNA 分子，已被发现参与卵母细胞功能、激素代谢以及颗粒细胞的增殖和凋亡的调控。在这项研究中，我们研究了卵泡液来源的外泌体中的 lncRNA 作用及其潜在机制。
方法：我们使用 RNA 测序分析了 PCOS 患者和对照组卵泡液来源的外泌体中的 lncRNA 图谱。通过 RT-qPCR 检测了对照组（n=30）和 PCOS 组（n=30）FF 外泌体样本中这些 lncRNA 的表达水平。此外，我们通过在体成熟（IVM）实验在小鼠中验证了 lncRNA LIPE-AS1 对卵母细胞成熟的作用，以及在颗粒细胞中验证了 lncRNA LIPE-AS1 对类固醇代谢的作用。
结果：我们发现 501 个 lncRNA 仅在对照组中特异性表达，另外 273 个 lncRNA 仅在 PCOS 组中特异性表达。在 PCOS 外泌体中高表达的 lncRNA LIPE-AS1 与 PCOS 患者卵母细胞成熟和胚胎发育不良有关。通过在体成熟（IVM）实验在小鼠中观察到 LIPE-AS1 组的 MII 卵母细胞数量减少。LIPE-AS1 还通过 LIPE-AS1/miR-4306/LHCGR 轴调节类固醇代谢以及颗粒细胞增殖和凋亡。
结论：这些发现表明，卵泡液外泌体中 LIPE-AS1 的表达增加对卵母细胞成熟和胚胎发育有显著影响。我们证明了涉及 LIPE-AS1、miR-4306 和 LHCGR 的 ceRNA 机制是激素产生和代谢的调节剂。这些发现表明 LIPE-AS1 在 PCOS 卵母细胞成熟中是必不可少的，并揭示了 LIPE-AS1 的 ceRNA 网络，为 PCOS 中异常类固醇代谢和卵母细胞发育提供了新信息。
Cell Biol Toxicol. 2025-6-17
Front Med (Lausanne). 2023-2-17
J Steroid Biochem Mol Biol. 2023-2
Cells. 2022-2-13
Adipocyte. 2022-12
Zotero 插件