Testosterone deficiency accompanied by testicular and epididymal abnormalities in TMF−/− mice

TMF/ARA160 is a Golgi-associated protein, which is essential for spermiogenesis. In this study, we show that lack of TMF/ARA160 leads to defects in both the testis and the epididymis. In the testis, spermatid retention and extensive proliferation of Leydig cells were observed. Concomitantly, the serum levels of luteinizing hormone (LH), a stimulator of Leydig cell proliferation, were significantly increased in TMF−/− mice. Structural and functional defects were also seen in the epididymis. These included apoptosis of epithelial epididymal cells and sperm stasis in the cauda. Notably, the serum testosterone levels of TMF−/− mice were significantly lower than those of wt mice, and external testosterone administration decreased the number of apoptotic epithelial epididymal cells in TMF−/− animals. In summary, we show here for the first time that TMF/ARA160 participates in the control of serum testosterone levels in males, and its absence results in major testicular and epididymal defects.

► TMF/ARA160 associates with the Golgi and ER organelles of testicular Leydig cells.
► Loss of TMF/ARA160 results in testicular and epididymal defects.
► Absence of TMF/ARA160 leads to a significantly decreased serum testosterone levels.
► External testosterone administration rescues epididymal apoptosis.
► TMF/ARA160 participates in the control of testosterone levels in mice.