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Angiotensin-converting enzyme and male fertility.

The angiotensin-converting enzyme (ACE; EC 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.

Pubmed ID: 9482924


  • Hagaman JR
  • Moyer JS
  • Bachman ES
  • Sibony M
  • Magyar PL
  • Welch JE
  • Smithies O
  • Krege JH
  • O'Brien DA


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

March 3, 1998

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM20069
  • Agency: NHLBI NIH HHS, Id: HL03470
  • Agency: NHLBI NIH HHS, Id: HL49277
  • Agency: NICHD NIH HHS, Id: R01 HD026485
  • Agency: NICHD NIH HHS, Id: U54 HD035041

Mesh Terms

  • Animals
  • Epididymis
  • Female
  • Fertility
  • Heterozygote Detection
  • In Situ Hybridization
  • Isoenzymes
  • Male
  • Mice
  • Mice, Knockout
  • Peptidyl-Dipeptidase A
  • RNA, Messenger
  • Sperm Capacitation
  • Sperm Motility
  • Sperm-Ovum Interactions
  • Spermatids
  • Spermatozoa
  • Testis
  • Transcription, Genetic
  • Zona Pellucida