Testosterone-Induced Metabolic Changes in Seminal Vesicle Epithelial cells Alter Plasma Components to Enhance Sperm Fertility

Male factors account for almost half of the causes of infertility. In rodents and humans, most of the components of semen are supplied by the seminal vesicles, and they support male reproductive ability, but there are many unknown details. In this study, the metabolic changes in the seminal vesicle epithelial cells were focused on, and the mechanisms by which testosterone affects the seminal plasma composition were investigated. A factor that improves the linear motility of sperm was secreted from the seminal vesicles, which were synthesized in an androgen-dependent manner. Bioassays, gene expression, and flux analysis studies demonstrated that testosterone promotes glucose uptake in seminal vesicle epithelial cells via GLUT4, resulting in oleic acid synthesis. Oleic acid was shown to be taken up by sperm and to promote linear motility, thereby improving fertilization rates both in vitro and in vivo. ACLY was a critical factor in this metabolic change, which produces oleic acid and enhances their fertilization ability in vivo. In conclusion, the critical role of testosterone-induced metabolic changes in the seminal vesicles is to ensure the synthesis of oleic acid, which is important for sperm fertilization in vivo. These findings provide new perspectives for the development of potential biomarkers of male fertility and advances in the treatment of male infertility.