SERINC4 is dispensable for male fertility and spermatogenesis in mice.

OBJECTIVES: Transmembrane proteins are known to play pivotal roles in spermatogenesis and male fertility. Recent transcriptomic analyses have suggested that the serine incorporator 4 (SERINC4), a multi-pass transmembrane protein, is highly expressed in testicular germ cells, yet its physiologic function in male reproduction remains unclear. This study aimed to investigate the in vivo role of SERINC4 in spermatogenesis and male fertility using a Serinc4-knockout (KO) mouse model. METHODS: Single-cell RNA sequencing (scRNA-seq) data were analyzed to determine the expression pattern of SERINC4 in human and Serinc4 in mouse testis. Serinc4-KO mice were generated by CRISPR/Cas9-mediated deletion of exon 5. Phenotypic analyses included fertility testing, testis histology, sperm evaluation using computer-assisted sperm analysis (CASA), immunofluorescence for germ and somatic cell markers, and TUNEL assay for germ cell apoptosis. RESULTS: Although scRNA-seq analyses revealed high SERINC4 expression in spermatids of human testes and high Serinc4 expression in spermatocytes of mouse testes, its deficiency did not impair male fertility, testicular morphology, or spermatogenesis in mice. No significant differences were observed between wild-type (WT) and Serinc4-KO mice in terms of sperm count, motility, or testis to body weight ratio. In addition, TUNEL assay revealed no significant change in germ cell apoptosis. CONCLUSIONS: Under physiologic conditions, Serinc4 appears to be dispensable for normal spermatogenesis and male fertility in mice. Future studies are needed to investigate its role under pathologic or aging-related conditions.