A team from the University of Osaka in Japan has used protein sequence data analysis and genome editing technology to discover that the SPATA33 molecule plays an important role in regulating sperm motility, thereby It will help develop male contraceptives , and research the cause of male infertility.
Calcineurin, a calcium-dependent phosphatase, was previously known to play an important role in regulating sperm motility. Calcineurin is considered a good target for male contraceptives because the administration of calcineurin inhibitors to male mice causes reversible infertility in a short period of time.
“However, since calcineurin also plays an important role in immunity, there is a problem that if calcineurin is inhibited in immune cells, immune function will also be suppressed . Therefore, our aim was to elucidate the mechanism that regulates the function of calcineurin specifically in sperm, “says corresponding author, Masahito Ikawa.
The research group focused on the PxIxIT motif that can be found in many proteins that bind to calcineurin. Of the approximately 20,000 mouse proteins, eight proteins were found to contain the PxIxIT motif and are predominantly expressed in the testes.
“Genome editing technology was then used to generate knockout mice for three of these proteins that had not been previously analyzed. As a result, the SPATA33 knockout mice showed impaired sperm motility and fertility defects, similar to the knockout mice of calcineurin, “explains lead author Haruhiko Miyata.
“Other analyzes revealed that SPATA33 regulates the localization of calcineurin,” he continues. “When SPATA33 is removed, calcineurin cannot localize to the central part of the sperm tail and it cannot bend, leading to impaired sperm motility.”
Targeting SPATA33 may lead to the development of male contraceptives that specifically inhibit the function of calcineurin in sperm. Furthermore, this study has clarified the mechanism by which SPATA33 controls sperm motility, adding a new perspective to the investigation and diagnosis of the cause of male infertility.
“We want to further clarify the mechanism of regulation of sperm motility by calcineurin in its entirety. We hope that our findings will lead to the development of fast-acting reversible male contraceptives and to the investigation of the cause of male infertility due to decreased sperm motility, “says Haruhiko Miyata.