Dipeptidase-inactivated tACE action in vivo: Selective inhibition of sperm-zona pellucida binding in the mouse
Dipeptidase-inactivated tACE action in vivo: Selective inhibition of sperm-zona pellucida binding in the mouse
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DOI：
10.1095/biolreprod.107.060004
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发表时间：
2007-11-01
影响因子：
3.6
通讯作者：
Kondoh, Gen
中科院分区：
文献类型：
--
作者：
Deguchi, Eishi;Tani, Taeko;Kondoh, Gen
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，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细胞特异性同工酶，其在生育中专门发挥ACE的作用，尽管作用的位点和方式尚不清楚。为了研究tACE在受精中的作用，我们生产了携带二肽酶失活突变体的转基因小鼠品系。尽管转基因小鼠显示出正常的血压、肾脏形态和生育能力，但在体外受精（IVF）后观察到受精减少。精子-透明带（ZP）结合在这些品系中以类似于在Ace基因敲除小鼠中观察到的方式专门受损。二肽酶活性在附睾成分中降低，但在睾丸中没有。此外，直接应用突变蛋白没有抑制精子ZP结合的完整精子在IVF，这意味着二肽酶失活的突变体影响精子修改附睾ZP结合。我们的研究结果表明，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有助于受精。
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 lVF, 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.