ANGIOTENSIN-CONVERTING ENZYME AND MALE-FERTILITY

The angiotensin-converting enzyme (ACE; EC 3.4.15.1) gene (Ace) encode s both a somatic isozyme found in blood and several other tissues, inc luding the epididymis, and a testis-specific isozyme (testis ACE) foun d only in developing spermatids and mature sperm. We recently used gen e targeting to disrupt the gene coding for both ACE isozymes in mice a nd reported that male homozygous mutants mate normally but have reduce d fertility; the mutant females are fertile. Here we explore the male fertility defect, We demonstrate that ACE is important for achieving i n vivo fertilization and that sperm from mice lacking both ACE isozyme s show defects in transport within the oviducts and in binding to zona e 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 a nd female mice lacking angiotensinogen have normal fertility, indicati ng that angiotensin I is not a necessary substrate for testis ACE. Mal es heterozygous for the mutation inactivating both ACE isozymes sire w ild-type and heterozygous offspring at an indistinguishable frequency, indicating no selection against sperm carrying the mutation.