Male fertility in Mus musculus requires the activity of TRYX5 in sperm migration into the oviduct.

Nowadays, abnormal loss of serine proteases appears very frequently in male patients with unexplained sterility. In fact, many testis-specific serine proteases, the largest family among the four protease families implicated in murine spermatogenesis, are indispensable for reproduction. In the present study, we demonstrate that the previously uncharacterized testis-specific serine protease TRYX5 (1700074P13Rik) is required for male fertility in mice. Tryx5(-/-) male mice are sterile, yet they have normal spermatogenesis and normal sperm parameters. In vivo fertilization experiments showed that the fertilization rate of Tryx5(-/-) sperm was almost zero. Sperm counting and analysis of paraffin sections of oviducts revealed that Tryx5(-/-) sperm were unable to migrate into the oviduct, which is likely the cause of the observed infertility of the Tryx5(-/-) male mice. Importantly, we also found that there was almost no mature ADAM3 present in Tryx5(-/-) sperm and almost no ADAM3 precursor in Tryx5(-/-) elongated spermatids of S13-16 stage, even though testes of Tryx5(-/-) and wild type mice had the same amount of the total precursor ADAM3. Collectively, our results demonstrate that Tryx5 is essential for male fertility in mice and suggest that TRYX5 functions in the stability or localization of ADAM3 precursor in elongated spermatids S13-16 stage, thereby regulating the ability of sperm to migrate from the uterus into the ampulla of the oviduct, the site of fertilization.