B3GALT4-dependent gangliosides are required for normal late spermatogenesis and male fertility

Gangliosides play important roles in membrane organization and cellular signaling. Although their involvement in spermatogenesis has been suggested, the specific functions of individual ganglioside species during each stage of germ cell development remain poorly understood. In this study, we generated beta-1,3-galactosyltransferase 4(B3galt4) knockout (KO) mice to investigate the role of B3GALT4-dependent ganglioside in male germ cell development. Immunostaining analyses demonstrated that B3galt4 deficiency caused selective alterations in ganglioside distribution. Although testis size did not differ significantly between KO and control mice, KO males were completely infertile. Histological examination revealed that spermatogenesis in KO mice proceeded to the elongating spermatid stage; however, abnormalities were observed during the late stages of spermatogenesis, including a reduced number of elongating/elongated spermatids and multinucleated giant cells in subsets of seminiferous tubules. Consistent with these observations, the number of sperm recovered from the cauda epididymis was markedly decreased, accompanied by morphological abnormalities and impaired motility. Collectively, these findings demonstrate that B3galt4 deficiency compromises late spermatogenesis and sperm function, resulting in male infertility. Our results further suggest that B3GALT4-dependent gangliosides have stage-dependent roles during late spermatogenesis and sperm development.