Submitted January 8, 2007
Returned for revision February 14, 2007
Accepted July 17, 2007
Gamete Biology
Dipeptidase-inactivated tACE Action In Vivo: Selective Inhibition of Sperm-Zona Pellucida Binding
Eishi Deguchi ,
Taeko Tani ,
Hitomi Watanabe ,
Shuichi Yamada ,
and
Gen Kondoh *
* To whom correspondence should be addressed. E-mail: kondohg{at}frontier.kyoto-u.ac.jp.
Abstract
The angiotensin-converting enzyme (ACE) plays a crucial role in male fertilization and is a key regulator of blood pressure. Testicular ACE (tACE), the germinal-specific isozyme expressed on different promoters, exclusively carries out the role of ACE in fertility, although the site and mode of action are not well known. To investigate the contribution of tACE in fertilization, we produced transgenic mouse lines carrying a dipeptidase-inactivated mutant. Although the transgenic mice showed normal blood pressure, kidney morphology, and fertility, reduced fertilization was observed after in vitro fertilization (IVF). The sperm-zona pellucida (ZP) binding was exclusively impaired in these lines, in a manner similar to that observed in Ace knockout mouse. The dipeptidase activity was reduced in epididymal ingredients but not in the testis. Furthermore, direct application of mutant protein did not suppress sperm-ZP binding of intact sperm during IVF, implying that the dipeptidase-inactivated mutant affects sperm modification in the epididymis for ZP binding. Our results indicate that the dipeptidase-inactivated tACE acts in vivo, suggesting that tACE contributes to fertilization as a dipeptidase at least in the epididymis.
Key words:
Testis •
Epididymis •
Fertilization •
In vitro fertilization •
Sperm
