Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul 03080, Korea.
Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University, Seoul 03080, Korea.
Int J Mol Sci. 2021 Oct 6;22(19):10819. doi: 10.3390/ijms221910819.
Female endocrinological symptoms, such as premature ovarian inefficiency (POI) are caused by diminished ovarian reserve and chemotherapy. The etiology of POI remains unknown, but this can lead to infertility. This has accelerated the search for master regulator genes or other molecules that contribute as enhancers or silencers. The impact of regulatory microRNAs (miRNAs) on POI has gained attention; however, their regulatory function in this condition is not well known. RNA sequencing was performed at four stages, 2-(2 W), 6-(6 W), 15-(15 W), and 20-(20 W) weeks, on ovarian tissue samples and 5058 differentially expressed genes (DEGs) were identified. Gene expression and enrichment were analyzed based on the gene ontology and KEGG databases, and their association with other proteins was assessed using the STRING database. Gene set enrichment analysis was performed to identify the key target genes. The DEGs were most highly enriched in 6 W and 15 W groups. , , , and were significantly in-creased at 2 W compared with levels at 6 W and 20 W, whereas the expression of , , and was significantly de-creased at 20 W. and expression was maintained at similar levels in each stage. In total, 27 genes were upregulated and 26 genes interacted with miRNAs; moreover, stage-specific upregulated and downregulated interactions were demonstrated. Increased and decreased miRNAs were identified at each stage in the ovaries. The constitutively expressed genes, and , were identified as the major targets of many miRNAs ( < 0.05), and and interacted with miRNAs, namely mmu-miR-670-3p and mmu-miR-153-3p. miR-26a-5p interacted with , and its target genes were downregulated in the 20 W mouse ovary. In this study, we aimed to identify key miRNAs and their target genes encompassing the reproductive span of mouse ovaries using mRNA and miRNA sequencing. These results indicated that gene sets are regulated in the reproductive stage-specific manner via interaction with miRNAs. Furthermore, consistent expression of and is considered crucial for the ovarian reserve and is regulated by many interactive miRNAs.
女性内分泌症状，如卵巢早衰（POI），是由卵巢储备减少和化疗引起的。POI 的病因尚不清楚，但这可能导致不孕。这加速了寻找主调控基因或其他作为增强子或沉默子的分子的研究。调节 microRNAs（miRNAs）对 POI 的影响引起了关注；然而，它们在这种情况下的调节功能尚不清楚。在卵巢组织样本上进行了四个阶段，2-(2 W)、6-(6 W)、15-(15 W)和 20-(20 W)的 RNA 测序，并鉴定了 5058 个差异表达基因（DEGs）。根据基因本体论和 KEGG 数据库分析基因表达和富集，并使用 STRING 数据库评估其与其他蛋白质的关联。进行基因集富集分析以确定关键靶基因。DEGs 在 6 W 和 15 W 组中高度富集。与 6 W 和 20 W 相比，2 W 时 、 、 和 显著增加，而 20 W 时 、 、 和 表达显著降低。和 表达在每个阶段均保持相似水平。总共 27 个基因上调，26 个基因与 miRNAs 相互作用；此外，还显示了阶段特异性的上调和下调相互作用。在每个阶段的卵巢中都发现了增加和减少的 miRNAs。组成型表达的基因 、 和 被鉴定为许多 miRNAs 的主要靶标（<0.05），并且 和 与 miRNAs 相互作用，即 mmu-miR-670-3p 和 mmu-miR-153-3p。miR-26a-5p 与 相互作用，其靶基因在 20 W 小鼠卵巢中下调。在这项研究中，我们旨在使用 mRNA 和 miRNA 测序鉴定涵盖小鼠卵巢生殖范围的关键 miRNAs 和它们的靶基因。这些结果表明，基因集通过与 miRNAs 相互作用以生殖阶段特异性方式进行调节。此外，和 的一致表达被认为对卵巢储备至关重要，并受许多相互作用的 miRNAs 调节。
