School of Medicine, Women's Hospital, Zhejiang University, 1 Xueshi Road, Shangcheng District, Hangzhou, 310006, China.
Key Laboratory of Reproductive Genetics, Ministry of Education Zhejiang University, Hangzhou, 310006, China.
J Ovarian Res. 2023 Aug 3;16(1):154. doi: 10.1186/s13048-023-01223-0.
Polycystic ovary syndrome (PCOS) is a common reproductive, neuroendocrine, and metabolic disorder in women of reproductive age that affects up to 5-10% of women of reproductive age. The aetiology of follicle development arrest and critical issues regarding the abnormal follicular development in PCOS remain unclear. The present study aims to systematically evaluate granulosa cell whole-transcriptome sequencing data to gain more insights into the transcriptomic landscape and molecular mechanism of PCOS in China.
In the present study, the microarray datasets GSE138518, GSE168404, GSE193123, GSE138572, GSE95728, and GSE145296 were downloaded from the Gene Expression Omnibus (GEO) database. Subsequently, differential expression analysis was performed on the PCOS and control groups, followed by functional interaction prediction analysis to investigate gene-regulatory circuits in PCOS. Finally, hub genes and their associated ncRNAs were validated by qPCR in human-luteinized granulosa (hGL) cells and were correlated with the clinical characteristics of the patients.
A total of 200 differentially expressed mRNAs, 3 differentially expressed miRNAs, 52 differentially expressed lncRNAs, and 66 differentially expressed circRNAs were found in PCOS samples compared with controls. GO and KEGG enrichment analyses indicated that the DEGs were mostly enriched in phospholipid metabolic processes, steroid biosynthesis and inflammation related pathways. In addition, the upregulated miRNA hsa-miR-205-5p was significantly enriched in the ceRNA network, and two hub genes, MVD and PNPLA3, were regulated by hsa-miR-205-5p, which means that hsa-miR-205-5p may play a fundamental role in the pathogenesis of PCOS. We also found that MVD and PNPLA3 were related to metabolic processes and ovarian steroidogenesis, which may be the cause of the follicle development arrest in PCOS patients.
In summary, we systematically constructed a ceRNA network depicting the interactions between the ncRNAs and the hub genes in PCOS and control subjects and correlated the hub genes with the clinical characteristics of the patients, which provides valuable insights into the granulosa cell whole-transcriptome landscape of PCOS in China.
多囊卵巢综合征（PCOS）是一种常见的生殖、神经内分泌和代谢紊乱，影响 5-10%的育龄妇女。卵泡发育停滞的病因和 PCOS 中异常卵泡发育的关键问题尚不清楚。本研究旨在系统评估颗粒细胞全转录组测序数据，以更深入地了解中国 PCOS 的转录组景观和分子机制。
本研究从基因表达综合数据库（GEO）下载了微阵列数据集 GSE138518、GSE168404、GSE193123、GSE138572、GSE95728 和 GSE145296。随后，对 PCOS 组和对照组进行差异表达分析，然后进行功能互作预测分析，以研究 PCOS 中的基因调控网络。最后，通过 qPCR 在人黄体化颗粒细胞（hGL）中验证了核心基因及其相关 ncRNA，并与患者的临床特征相关联。
与对照组相比，PCOS 样本中共有 200 个差异表达的 mRNAs、3 个差异表达的 miRNAs、52 个差异表达的 lncRNAs 和 66 个差异表达的 circRNAs。GO 和 KEGG 富集分析表明，DEGs 主要富集在磷脂代谢过程、类固醇生物合成和炎症相关途径中。此外，上调的 miRNA hsa-miR-205-5p 在 ceRNA 网络中显著富集，两个核心基因 MVD 和 PNPLA3 受 hsa-miR-205-5p 调控，这意味着 hsa-miR-205-5p 可能在 PCOS 的发病机制中起重要作用。我们还发现 MVD 和 PNPLA3 与代谢过程和卵巢类固醇生成有关，这可能是 PCOS 患者卵泡发育停滞的原因。
总之，我们系统地构建了一个 ceRNA 网络，描述了 PCOS 和对照组中 ncRNA 和核心基因之间的相互作用，并将核心基因与患者的临床特征相关联，这为我们提供了有价值的见解，了解中国 PCOS 颗粒细胞的全转录组景观。
