Molecular Features of Polycystic Ovary Syndrome Revealed by Transcriptome Analysis of Oocytes and Cumulus Cells.
Molecular Features of Polycystic Ovary Syndrome Revealed by Transcriptome Analysis of Oocytes and Cumulus Cells.
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DOI：
10.3389/fcell.2021.735684
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发表时间：
2021
影响因子：
5.5
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Li J;Chen H;Gou M;Tian C;Wang H;Song X;Keefe DL;Bai X;Liu L
多囊卵巢综合征（PCOS）的典型特征是多囊卵巢形态、高雄激素血症、排卵功能障碍和不孕。此外，接受卵巢刺激的PCOS患者有更多的卵母细胞;然而，卵母细胞的质量差导致受精率和着床率降低，妊娠率降低，流产率增加。PCOS和卵母细胞质量差的复杂分子机制仍有待阐明。我们从PCOS患者中获得了匹配的卵母细胞和卵丘细胞（CC），将其与年龄匹配的对照组进行比较，并进行RNA测序分析，以探讨其卵母细胞和CC的转录特征。此外，我们通过免疫荧光验证了我们新确认的PCOS候选基因。无监督聚类分析显示，PCOS患者的整体基因表达模式和转座因子（TE）表达谱紧密聚集在一起，与对照组明显不同。在PCOS卵母细胞中发现了功能重要的通路的异常。值得注意的是，参与微管过程的基因TUBB 8和TUBA 1C在PCOS卵母细胞中过表达。代谢和氧化磷酸化途径也在PCOS患者的卵母细胞和CC中失调。此外，在卵母细胞中，差异表达的TE并不均匀地分散在人类染色体中。位于染色体2、3、4和5上的内源性逆转录病毒1（ERV 1）元件相当高度上调。有趣的是，这些与最高表达的蛋白质编码基因相关，包括微管蛋白相关基因TUBA 1C，TUBB 8 P8和TUBB 8，将ERV 1元件与PCOS的发生联系起来。我们综合分析了卵母细胞和CC中的基因表达，包括TE表达，揭示了PCOS的特异性分子特征。TUBB 8和TUBA 1C和ERV 1的异常升高表达为PCOS提供了额外的标志物，并可能导致PCOS患者卵母细胞发育能力受损。我们的研究结果也可能对改善卵母细胞成熟的治疗策略和PCOS妇女的妊娠结局有影响。
Polycystic ovary syndrome (PCOS) is typically characterized by a polycystic ovarian morphology, hyperandrogenism, ovulatory dysfunction, and infertility. Furthermore, PCOS patients undergoing ovarian stimulation have more oocytes; however, the poor quality of oocytes leads to lower fertilization and implantation rates, decreased pregnancy rates, and increased miscarriage rates. The complex molecular mechanisms underlying PCOS and the poor quality of oocytes remain to be elucidated. We obtained matched oocytes and cumulus cells (CCs) from PCOS patients, compared them with age-matched controls, and performed RNA sequencing analysis to explore the transcriptional characteristics of their oocytes and CCs. Moreover, we validated our newly confirmed candidate genes for PCOS by immunofluorescence. Unsupervised clustering analysis showed that the overall global gene expression patterns and transposable element (TE) expression profiles of PCOS patients tightly clustered together, clearly distinct from those of controls. Abnormalities in functionally important pathways are found in PCOS oocytes. Notably, genes involved in microtubule processes, TUBB8 and TUBA1C, are overexpressed in PCOS oocytes. The metabolic and oxidative phosphorylation pathways are also dysregulated in both oocytes and CCs from PCOS patients. Moreover, in oocytes, differentially expressed TEs are not uniformly dispersed in human chromosomes. Endogenous retrovirus 1 (ERV1) elements located on chromosomes 2, 3, 4, and 5 are rather highly upregulated. Interestingly, these correlate with the most highly expressed protein-coding genes, including tubulin-associated genes TUBA1C, TUBB8P8, and TUBB8, linking the ERV1 elements to the occurrence of PCOS. Our comprehensive analysis of gene expression in oocytes and CCs, including TE expression, revealed the specific molecular features of PCOS. The aberrantly elevated expression of TUBB8 and TUBA1C and ERV1 provides additional markers for PCOS and may contribute to the compromised oocyte developmental competence in PCOS patients. Our findings may also have implications for treatment strategies to improve oocyte maturation and the pregnancy outcomes for women with PCOS.
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