The role of heterogeneous nuclear ribonucleoproteins in mammalian spermatogenesis: mechanisms and clinical implications

In brief: As a major family of RNA binding proteins, heterogeneous nuclear ribonucleoproteins (hnRNPs) are involved in the entire RNA metabolism process and have been increasingly recognized as essential regulators of spermatogenesis. This review systematically summarizes the latest advances in the functions, molecular mechanisms, and clinical applications of hnRNPs in mammalian spermatogenesis. Abstract: Spermatogenesis in mammals is a complex and highly orchestrated process of cellular development that necessitates precise regulation at the transcriptional, post-transcriptional, and translational levels. RNA binding proteins (RBPs) are integral to this process, particularly due to the occurrence of two transcriptional arrest phases in spermatogenic cells. Among these RBPs, heterogeneous nuclear ribonucleoproteins (hnRNPs) constitute a significant family that engages in the entire RNA metabolism process through various RNA-binding domains. Recent research has underscored their essential role in mammalian spermatogenesis. This article provides a comprehensive review of the expression patterns of hnRNP proteins and elucidates their mechanisms of action during critical stages of spermatogenesis, including the maintenance and differentiation of spermatogonial stem cells, meiosis in spermatocytes, and the formation and maturation of sperm. It further examines their functions in supporting cellular development, proliferation, and the maintenance of the blood-testis barrier. Additionally, the article explores the association between aberrant hnRNP proteins and male infertility, highlighting their potential clinical applications, and summarizes recent advancements in the field. This review provides theoretical references for in-depth analysis of the molecular regulatory network of spermatogenesis, and also opens up new directions for clinical diagnosis and treatment of male infertility.