title: Partial deletion of chromosome 8 β-defensin cluster confers sperm dysfunction and infertility in male mice.
abstract: β-defensin peptides are a family of antimicrobial peptides present at mucosal surfaces, with the main site of expression under normal conditions in the male reproductive tract. Although they kill microbes in vitro and interact with immune cells, the precise role of these genes in vivo remains uncertain. We show here that homozygous deletion of a cluster of nine β-defensin genes (DefbΔ9) in the mouse results in male sterility. The sperm derived from the mutants have reduced motility and increased fragility. Epididymal sperm isolated from the cauda should require capacitation to induce the acrosome reaction but sperm from the mutants demonstrate precocious capacitation and increased spontaneous acrosome reaction compared to wild-types but have reduced ability to bind the zona pellucida of oocytes. Ultrastructural examination reveals a defect in microtubule structure of the axoneme with increased disintegration in mutant derived sperm present in the epididymis cauda region, but not in caput region or testes. Consistent with premature acrosome reaction, sperm from mutant animals have significantly increased intracellular calcium content. Thus we demonstrate in vivo that β-defensins are essential for successful sperm maturation, and their disruption leads to alteration in intracellular calcium, inappropriate spontaneous acrosome reaction and profound male infertility.
authors.affiliation: MRC Human Genetics Unit, MRC IGMM, University of Edinburgh, Western General Hospital, Edinburgh, Scotland, United Kingdom.
authors.forename: Yu S
authors.initials: YS
authors.lastname: Zhou
authors.forename: Sheila
authors.initials: S
authors.lastname: Webb
authors.forename: Laura
authors.initials: L
authors.lastname: Lettice
authors.forename: Steve
authors.initials: S
authors.lastname: Tardif
authors.forename: Fiona
authors.initials: F
authors.lastname: Kilanowski
authors.forename: Christine
authors.initials: C
authors.lastname: Tyrrell
authors.forename: Heather
authors.initials: H
authors.lastname: Macpherson
authors.forename: Fiona
authors.initials: F
authors.lastname: Semple
authors.forename: Peter
authors.initials: P
authors.lastname: Tennant
authors.forename: Tina
authors.initials: T
authors.lastname: Baker
authors.forename: Alan
authors.initials: A
authors.lastname: Hart
authors.forename: Paul
authors.initials: P
authors.lastname: Devenney
authors.forename: Paul
authors.initials: P
authors.lastname: Perry
authors.forename: Tracey
authors.initials: T
authors.lastname: Davey
authors.forename: Perdita
authors.initials: P
authors.lastname: Barran
authors.forename: Chris L
authors.initials: CL
authors.lastname: Barratt
authors.forename: Julia R
authors.initials: JR
authors.lastname: Dorin
mesh_terms: D000818:Animals; D002872:Chromosome Deletion; D002875:Chromosomes / Q000235:genetics / Q000378:metabolism; D007248:Infertility, Male / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D013079:Sperm Maturation / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism* / Q000473:pathology; D023083:beta-Defensins / Q000235:genetics*
chemical_list: D023083:beta-Defensins