Sun Qian, Li Yanyu, Yang Wen, Feng Wen, Zhou Jiayun, Cao Yijuan, Zhang Bei, Zhu Zuobin, Han Conghui
Suzhou Medical College, Soochow University, Suzhou, 215123, China.
Department of Gynecology, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, 222061, China.
Mol Biomed. 2024 Dec 13;5(1):69. doi: 10.1186/s43556-024-00236-5.
This study aimed to investigate the influence of sperm miRNAs on fertilization rates (FR) in in vitro fertilization (IVF) and to explore potential regulatory mechanisms in sperm-mediated fertilization and embryo development. Through high-throughput sequencing, we identified differentially expressed miRNAs in sperm, with miR-133a-3p significantly upregulated in samples associated with low FR and available embryo rate (AER). Key regulatory circRNAs and mRNAs were further identified via the Starbase database, intersected with differentially expressed RNA, and analyzed through GO, KEGG, and PPI analyses. The circMYH9/miR-133a-3p/CXCR4 axis emerged as a critical regulatory network. In vitro assays using the GC-2 spd mouse spermatogenic cell line revealed that miR-133a-3p inhibited cell growth and proliferation while promoting apoptosis. circMYH9, acting as a competing endogenous RNA (ceRNA) for miR-133a-3p, modulated CXCR4 expression, enhancing GC-2 spd cell growth and inhibiting apoptosis through the miR-133a-3p/CXCR4 axis. In vivo experiments using a mouse model confirmed that circMYH9 overexpression increased IVF success rates and promoted embryo development via this axis. Mechanistically, miR-133a-3p suppresses sperm fertilization and embryo development by targeting the circMYH9/miR-133a-3p/CXCR4 axis. These findings suggest that this regulatory network could serve as a novel biomarker for assessing fertilization potential and embryo quality in clinical settings and as a potential therapeutic target to improve IVF outcomes and address infertility. This study provides valuable insights into the molecular mechanisms governing sperm function and early embryonic development.
本研究旨在探讨精子微小RNA（miRNA）对体外受精（IVF）受精率（FR）的影响，并探索精子介导的受精和胚胎发育中的潜在调控机制。通过高通量测序，我们鉴定了精子中差异表达的miRNA，其中miR-133a-3p在与低FR和可用胚胎率（AER）相关的样本中显著上调。通过Starbase数据库进一步鉴定关键调控环状RNA（circRNA）和信使核糖核酸（mRNA），与差异表达的RNA进行交集分析，并通过基因本体论（GO）、京都基因与基因组百科全书（KEGG）和蛋白质-蛋白质相互作用（PPI）分析进行分析。circMYH9/miR-133a-3p/CXCR4轴成为一个关键的调控网络。使用GC-2 spd小鼠生精细胞系进行的体外试验表明，miR-133a-3p抑制细胞生长和增殖，同时促进细胞凋亡。circMYH9作为miR-133a-3p的竞争性内源性RNA（ceRNA），调节CXCR4表达，通过miR-133a-3p/CXCR4轴增强GC-2 spd细胞生长并抑制细胞凋亡。使用小鼠模型进行的体内实验证实，circMYH9的过表达通过该轴提高了IVF成功率并促进了胚胎发育。从机制上讲，miR-133a-3p通过靶向circMYH9/miR-133a-3p/CXCR4轴抑制精子受精和胚胎发育。这些发现表明，该调控网络可作为评估临床环境中受精潜力和胚胎质量的新型生物标志物，并作为改善IVF结果和解决不孕症的潜在治疗靶点。本研究为精子功能和早期胚胎发育的分子机制提供了有价值的见解。
