Deguchi Eishi, Tani Taeko, Watanabe Hitomi, Yamada Shuichi, Kondoh Gen
Institute for Frontier Medical Sciences, Kyoto University, Japan.
Biol Reprod. 2007 Nov;77(5):794-802. doi: 10.1095/biolreprod.107.060004. Epub 2007 Jul 18.
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 an 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.
血管紧张素转换酶（ACE）在男性受精过程中起着至关重要的作用，并且是血压的关键调节因子。睾丸ACE（tACE）是在不同启动子上表达的生殖特异性同工酶，尽管其作用位点和作用方式尚不清楚，但它在生育过程中专门发挥ACE的作用。为了研究tACE在受精中的作用，我们构建了携带二肽酶失活突变体的转基因小鼠品系。尽管转基因小鼠的血压、肾脏形态和生育能力正常，但体外受精（IVF）后观察到受精率降低。在这些品系中，精子与透明带（ZP）的结合以与Ace基因敲除小鼠中观察到的方式类似的方式受到特异性损害。附睾成分中的二肽酶活性降低，但睾丸中的二肽酶活性未降低。此外，在IVF期间直接应用突变蛋白并未抑制完整精子的精子-ZP结合，这意味着二肽酶失活突变体影响附睾中精子的修饰以实现与ZP的结合。我们的结果表明，二肽酶失活的tACE在体内起作用，这表明tACE至少在附睾中作为二肽酶对受精有贡献。
