Arrdc5, an α -arrestin molecule, is essential for mammalian spermatogenesis. It may be involved in cellular signaling and ubiquitination processes, as arrestin molecules generally act as modulators of these pathways [1]. Multispecies testicular tissue transcriptome profiling indicates its testis-enriched expression in mice, pigs, cattle, and humans [1].

Gene knockout studies in mice have revealed its crucial role. Arrdc5 knockout in mice leads to male-specific sterility, as sperm produced are low in number, immotile, and malformed [1]. Spermiogenesis, the final phase of spermatogenesis, is defective in Arrdc5-deficient mice, and epididymal sperm cannot capacitate and fertilize oocytes [1]. Another study shows that Arrdc5 deficiency impairs spermatogenesis by affecting SUN5 and NDC1, and might influence the vesicle-trafficking protein SEC22A-mediated transport and localization of proteins responsible for sperm head-tail coupling [2].

In conclusion, Arrdc5 is an essential regulator of mammalian spermatogenesis, and its deficiency leads to male infertility due to defects in sperm morphogenesis, motility, and capacitation. The gene knockout mouse models have been instrumental in uncovering its role in spermatogenesis, providing potential insights for male contraception and understanding the mechanisms of male infertility [1,2].

References:

1. Giassetti, Mariana I, Miao, Deqiang, Law, Nathan C, Bernhardt, Miranda L, Oatley, Jon M. 2023. ARRDC5 expression is conserved in mammalian testes and required for normal sperm morphogenesis. In Nature communications, 14, 2111. doi:10.1038/s41467-023-37735-y. https://pubmed.ncbi.nlm.nih.gov/37069147/

2. Liu, Ruyi, Qu, Ronggui, Li, Qun, Zhang, Zhihua, Sang, Qing. 2023. ARRDC5 deficiency impairs spermatogenesis by affecting SUN5 and NDC1. In Development (Cambridge, England), 150, . doi:10.1242/dev.201959. https://pubmed.ncbi.nlm.nih.gov/37997706/