Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
Department of Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
Int J Med Sci. 2021 Feb 6;18(7):1670-1679. doi: 10.7150/ijms.54460. eCollection 2021.
Asthenozoospermia, one of the most common causes of male infertility, is a complicate multifactorial pathological condition that genetic factors are involved in. However, the epigenetic signature and mechanism of asthenozoospermia still remain limited. Our study aimed to confirm the key microRNAs (miRNAs) and genes in asthenozoospermia and demonstrate the underlying epigenetic regulatory mechanisms. We screened out and pooled previous studies to extracted potential differentially expressed miRNAs (DEMs). GSE22331 and a published profile dataset were integrated to identify differentially expressed genes (DEGs). Pathway and gene ontology analysis were performed using DAVID. A protein-protein network (PPI) was constructed using STRING. The target genes of DEMs were predicted using TargetScan and the miRNA-mRNA network was built. We reported 3 DEMs and 423 DEGs by pooling included dataset and published studies. Pathway analysis showed that these DEGs might participate in signaling pathways regulating pluripotency of stem cells, Wnt signaling pathway and Notch signaling pathway. 25 hub genes were identified, and the most significant gene was BDNF. We screened out the overlapped DEGs between the predicted target genes of 3 DEMs and the 423 DEGs. Finally, a potential miRNA-mRNA regulatory network was constructed. This study firstly pooled several published studies and a GEO dataset to determine the significance of potential miRNAs and genes, such as miR-374b, miR-193a, miR-34b, BDNF, NTRK2, HNRNPD and EFTUD2 in regulating asthenozoospermia and underscore their interactions in the pathophysiological mechanism. Our results provided theoretical basis and new clues for potential therapeutic treatment in asthenozoospermia. Validations and are required in future studies.
弱精症是男性不育症最常见的原因之一,是一种复杂的多因素病理状态,涉及遗传因素。然而,弱精症的表观遗传特征和机制仍有限。本研究旨在确认弱精症中的关键 microRNAs (miRNAs) 和基因,并阐明潜在的表观遗传调控机制。我们筛选并汇总了以前的研究,以提取潜在的差异表达 miRNAs (DEMs)。整合 GSE22331 和已发表的基因表达谱数据集,以鉴定差异表达基因 (DEGs)。使用 DAVID 进行途径和基因本体论分析。使用 STRING 构建蛋白质-蛋白质网络 (PPI)。使用 TargetScan 预测 DEMs 的靶基因,并构建 miRNA-mRNA 网络。通过汇总纳入数据集和已发表的研究,我们报告了 3 个 DEMs 和 423 个 DEGs。途径分析表明,这些 DEGs 可能参与调节干细胞多能性、Wnt 信号通路和 Notch 信号通路的信号通路。鉴定出 25 个枢纽基因,其中最显著的基因是 BDNF。我们筛选出 3 个 DEMs 的预测靶基因与 423 个 DEGs 之间的重叠 DEGs。最后,构建了一个潜在的 miRNA-mRNA 调控网络。本研究首次汇总了几项已发表的研究和 GEO 数据集,以确定潜在 miRNAs 和基因(如 miR-374b、miR-193a、miR-34b、BDNF、NTRK2、HNRNPD 和 EFTUD2)在调节弱精症中的意义,并强调它们在病理生理机制中的相互作用。我们的研究结果为弱精症的潜在治疗提供了理论基础和新线索。未来的研究需要验证。