Angiotensin-converting enzyme and male fertility
Angiotensin-converting enzyme and male fertility
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DOI：
10.1073/pnas.95.5.2552
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发表时间：
1998-03-03
影响因子：
11.1
通讯作者：
O'Brien, DA
中科院分区：
文献类型：
--
作者：
Hagaman, JR;Moyer, JS;O'Brien, DA
血管紧张素转换酶（ACE；EC 3.4.15.1）基因 (Ace) 编码在血液和其他几个组织（包括附睾）中发现的体细胞同工酶，以及仅在发育中的精子细胞和成熟精子中发现的睾丸特异性同工酶（睾丸 ACE）。我们最近使用基因打靶来破坏小鼠体内两种 ACE 同工酶的基因编码，并报道雄性纯合突变体可以正常交配，但生育能力降低；突变的雌性具有生育能力。在这里，我们探讨了雄性生育缺陷，我们证明ACE对于实现体内受精很重要，并且缺乏两种ACE同工酶的小鼠的精子在输卵管内运输和与透明带结合方面表现出缺陷，通过基因靶向产生的缺乏体细胞ACE但保留睾丸ACE的雄性通常具有生育能力，证实雄性中的体细胞ACE对其生育能力不是必需的，此外，缺乏血管紧张素原的雄性和雌性小鼠具有正常的生育能力，这表明血管紧张素 I 不是睾丸 ACE 的必要底物。具有使 ACE 同工酶失活的突变的杂合雄性以无法区分的频率繁殖野生型和杂合子后代，表明没有针对携带该突变的精子的选择。
The angiotensin-converting enzyme (ACE; EC 3.4.15.1) gene (Ace) encodes both a somatic isozyme found in blood and several other tissues, including the epididymis, and a testis-specific isozyme (testis ACE) found only in developing spermatids and mature sperm. We recently used gene targeting to disrupt the gene coding for both ACE isozymes in mice and reported that male homozygous mutants mate normally but have reduced fertility; the mutant females are fertile. Here we explore the male fertility defect, We demonstrate that ACE is important for achieving in vivo fertilization and that sperm from mice lacking both ACE isozymes show defects in transport within the oviducts and in binding to zonae pellucidae, Males generated by gene targeting that lack somatic ACE but retain testis ACE are normally fertile, establishing that somatic ACE in males is not essential for their fertility, Furthermore, male and female mice lacking angiotensinogen have normal fertility, indicating that angiotensin I is not a necessary substrate for testis ACE. Males heterozygous for the mutation inactivating both ACE isozymes sire wild-type and heterozygous offspring at an indistinguishable frequency, indicating no selection against sperm carrying the mutation.