title: Angiotensin-converting enzyme and male fertility.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599-7525, USA. hage@med.unc.edu
authors.forename: J R
authors.initials: JR
authors.lastname: Hagaman
authors.forename: J S
authors.initials: JS
authors.lastname: Moyer
authors.forename: E S
authors.initials: ES
authors.lastname: Bachman
authors.forename: M
authors.initials: M
authors.lastname: Sibony
authors.forename: P L
authors.initials: PL
authors.lastname: Magyar
authors.forename: J E
authors.initials: JE
authors.lastname: Welch
authors.forename: O
authors.initials: O
authors.lastname: Smithies
authors.forename: J H
authors.initials: JH
authors.lastname: Krege
authors.forename: D A
authors.initials: DA
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D004822:Epididymis / Q000201:enzymology; D005260:Female; D005298:Fertility / Q000235:genetics*; D006580:Genetic Carrier Screening; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000096:biosynthesis; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D013075:Sperm Capacitation; D013081:Sperm Motility; D013084:Sperm-Ovum Interactions; D013087:Spermatids / Q000201:enzymology; D013094:Spermatozoa / Q000201:enzymology; D013737:Testis / Q000201:enzymology*; D014158:Transcription, Genetic; D015044:Zona Pellucida / Q000502:physiology
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A