The microRNA-mediated apoptotic signaling axis in male reproduction: a possible and targetable culprit in male infertility

作者：Pengxia Yu, Xue Zhao, Dan Zhou, Songtao Wang, Zhong Hu, Kai Lian, N. Yamamoto X. Zhang, Peng Duan · 发表于：Cell Biology and Toxicology · 年份：2025 · DOI：10.1007/s10565-025-10006-w · 被引用次数：19 · 研究领域：MicroRNA in disease regulation、Circular RNAs in diseases、Sperm and Testicular Function

Recently, infertility has emerged as a significant and prevalent public health concern warranting considerable attention. Apoptosis, recognized as programmed cell death, constitutes a crucial process essential for the maintenance of normal spermatogenesis. Multiple investigations have illustrated that the dysregulated apoptosis of reproductive cells, encompassing spermatogonial stem cells, Sertoli cells, and Leydig cells, serves as a causative factor in male infertility. MicroRNAs represent a class of small RNA molecules that exert negative regulatory control over gene expression using direct interaction with messenger RNA transcripts. Previous studies have established that aberrant expression of miRNAs induces apoptosis in reproductive tissues, correlating with reproductive dysfunctions and infertility. In this review, we offer a comprehensive overview of miRNAs and their respective target genes implicated in the apoptotic process. As well, miRNAs are involved in multiple apoptotic signaling pathways, namely the PI3K/AKT, NOTCH, Wnt/β-catenin, and mTOR signaling cascades, exerting both negative and positive effects. We additionally elucidate the significant functions played by lncRNAs and circular RNAs as competing endogenous RNAs in the process of apoptosis within reproductive cells. We further illustrate that external factors, including silica nanoparticles, Cyclosporine A, and smoking, induce dysregulation of miRNAs, resulting in apoptosis within reproductive cells and su...