Deficiency of LARP1 Impairs Spermatogenesis and Leads to Male Subfertility in Mice

Mammalian spermatogenesis is a complex process involving precisely regulated transcription and translation. The RNA-binding protein La ribonucleoprotein domain family member 1 (LARP1) is a member of the LARP family whose role in mammalian spermatogenesis is unclear. This study demonstrates that Larp1 is essential for normal spermatogenesis in mice. Deficiency of Larp1 in male germ cells disrupted meiotic progression and triggered apoptosis, leading to germ cell depletion. Furthermore, it caused aberrant spermatid flagella assembly alongside defects in sperm head morphology and acrosome structure. These cellular abnormalities culminated in impaired sperm motility and a significant reduction in male fertility. Transcriptomic analysis revealed that Larp1 loss upregulates pro-apoptotic genes and hyperactivates the p38 MAPK/p53 pathways, concomitant with the downregulation of genes essential for spermatogenesis, flagellar assembly, acrosome formation, and sperm motility. This altered expression profile thereby provides a mechanistic basis for the observed phenotypic defects. In contrast, female mutant mice exhibited normal oocyte development and fertility. In summary, this study establishes LARP1 as essential for spermatogenesis and male fertility in mice.