(A) Western blot images of ACLY and α/β-tubulin in three sets of seminal vesicle epithelial cells cultured with 100 ng/ml testosterone (Testo) or in vehicle (Ctrl) for 7 days. The addition of testosterone significantly increased the amount of ACLY protein in seminal vesicle epithelial cells (Figure 7A, B). (D) Western blot images of GLUT4 and α/β-tubulin in three sets of seminal vesicle epithelial cells cultured with 100 ng/ml testosterone (Testo) or in vehicle (Ctrl) for 7 days. This important work elucidates the biological processes and detailed mechanisms by which testosterone influences seminal plasma metabolites in mice. The contaminating cell type was considered to be mainly muscle cells because the gene expression levels of muscle cell markers verified by RNA-seq were relatively high. The seminal vesicle secretions from flutamide-treated mice were also collected similarly. (C) shRNA knockdown experiments of ACLY in seminal vesicle epithelial cells. Fatty acid synthesis is an important function of the seminal vesicles, and it was found that when testosterone is present, fatty acid synthesis enhancement and cell proliferation stop simultaneously. Immunostaining results showed that ACLY was detected specifically in seminal vesicle epithelial cells, and their staining appeared to be reduced by flutamide treatment. Therefore, the primary culture of seminal vesicle epithelial cells used in this experiment was considered to maintain the characteristics of seminal vesicle epithelial cells in vivo. Therefore, seminal vesicle epithelial cells were collected and cultured in primary culture, as shown in Figure 2D. These changes of abnormal morphology and high proliferation activity were also observed in seminal vesicles of mice older than 12 months that showed low serum testosterone levels (Figure 1—figure supplement 2D–F). (H) Experimental design to evaluate the effect of seminal vesicle secretions collected from male mice treated with or without flutamide (50 mg/kg subcutaneously every day for 7 days) on sperm. This study advances our understanding of the role of testosterone in glucose metabolism and fatty acid synthesis and lays the groundwork for future research in reproductive biology and fertility. The interspecies differences between humans and mice should be interpreted with caution, and the translational aspects to humans are speculative, but this study revealed a testosterone-dependent mechanism of oleic acid production in seminal vesicle epithelium. In the present study, induction of ACLY expression by testosterone not only decreased cycling in the TCA cycle but also promoted glucose assimilation, which played an important role in fatty acid synthesis. This study suggests that fatty acid synthesis is an important function of the seminal vesicles, which provide an environment where the ejaculated sperm can carry out active metabolism. Moreover, though the motility of ejaculated spermatozoa is known to decrease with aging, few reports have revealed age-related changes in the seminal vesicles, which are responsible for seminal plasma synthesis. The testosterone-induced change was also detected in in vivo samples (seminal vesicle), where the expression of Elovl6 was decreased by the flutamide treatment (Figure 6—figure supplement 1B). Indinavir, a functional inhibitor of GLUT4, significantly suppressed glucose uptake and significantly decreased fatty acid synthesis (the amount of fatty acids accumulated in the cell), which was increased by testosterone (Figure 6A, B). Male Excel l’s Testosterone Lipoderm Cream is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. It is not known if Male Excel’s Testosterone Lipoderm Cream is safe or effective in treating men who have low testosterone due to aging. Male Excel’s Testosterone Lipoderm Cream is a controlled substance (CIII) because it contains testosterone that can be a target for people who abuse prescription medicines. Based on DEA and state laws, your testosterone treatment plan may require an in-person medical exam. For men considering medical intervention for low testosterone, Male Excel offers Testosterone Replacement Therapy programs, including topical creams, along with optional ED medications when needed. If you're struggling with fertility or simply want to safeguard your reproductive health, don't ignore your hormones. Early diagnosis can significantly improve the effectiveness of testosterone treatments such as hormone therapy, medications like clomiphene or hCG, or assisted reproductive techniques like IUI or IVF. In this study, metabolic abnormalities induced by inhibition of androgen receptor function caused abnormal proliferation of seminal vesicle epithelial cells in aged mice. In the present study, the nuclear localization of AR in seminal vesicle epithelial cells (i.e., functioning as a transcription factor) and the activation of the glycolytic system by testosterone were similar to those in the above cell types. (J) Lipid accumulation in the medium where human seminal vesicle epithelial cells were incubated for 24 hr. (K–M) Fatty acid composition in the cultured supernatants was analyzed using gas chromatography. Thus, sperm formation occurs in the testis; they mature in the epididymis but only acquire the in vivo fertilization ability after exposure to seminal plasma. 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. The increase in motility is still small and far from comparable to the motility increase with seminal vesicle fluid. These results suggest that the enhancement of motility by lipids is functionally distinct from the capacitation-inhibiting function of seminal plasma proteins. As a result, the cleavage rate after in vitro fertilization using sperm exposed to seminal vesicle fluid decreased dramatically. "These findings suggest that testosterone-dependent lipid remodeling may contribute to sperm straight-line motility, and further functional verification is required."
