title: Targeted inactivation of the mouse epididymal beta-defensin 41 alters sperm flagellar beat pattern and zona pellucida binding.
abstract: During epididymal maturation, sperm acquire the ability to swim progressively by interacting with proteins secreted by the epididymal epithelium. Beta-defensin proteins, expressed in the epididymis, continue to regulate sperm motility during capacitation and hyperactivation in the female reproductive tract. We characterized the mouse beta-defensin 41 (DEFB41), by generating a mouse model with iCre recombinase inserted into the first exon of the gene. The homozygous Defb41(iCre/iCre) knock-in mice lacked Defb41 expression and displayed iCre recombinase activity in the principal cells of the proximal epididymis. Heterozygous Defb41(iCre/+) mice can be used to generate epididymis specific conditional knock-out mouse models. Homozygous Defb41(iCre/iCre) sperm displayed a defect in sperm motility with the flagella primarily bending in the pro-hook conformation while capacitated wild-type sperm more often displayed the anti-hook conformation. This led to a reduced straight line motility of Defb41(iCre/iCre) sperm and weaker binding to the oocyte. Thus, DEFB41 is required for proper sperm maturation.
authors.affiliation: Department of Physiology and Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland; Turku Doctoral Programme of Biomedical Sciences, Turku, Finland.
authors.forename: Ida
authors.initials: I
authors.lastname: Björkgren
authors.affiliation: Center of Advanced European Studies and Research (Caesar), Department of Molecular Sensory Systems, Bonn, Germany.
authors.forename: Luis
authors.initials: L
authors.lastname: Alvarez
authors.affiliation: Center of Advanced European Studies and Research (Caesar), Minerva Research Group Molecular Physiology, Bonn, Germany.
authors.forename: Nelli
authors.initials: N
authors.lastname: Blank
authors.affiliation: Center of Advanced European Studies and Research (Caesar), Minerva Research Group Molecular Physiology, Bonn, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Balbach
authors.affiliation: Department of Physiology and Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland; Turku Doctoral Programme of Biomedical Sciences, Turku, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Turunen
authors.affiliation: Department of Mathematics and Statistics, University of Turku, Turku, Finland; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
authors.forename: Teemu Daniel
authors.initials: TD
authors.lastname: Laajala
authors.affiliation: Department of Physiology and Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Toivanen
authors.affiliation: Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, United Kingdom.
authors.forename: Anton
authors.initials: A
authors.lastname: Krutskikh
authors.affiliation: Department of Biology, Lund University, Lund, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Wahlberg
authors.affiliation: Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London, United Kingdom.
authors.forename: Ilpo
authors.initials: I
authors.lastname: Huhtaniemi
authors.affiliation: Department of Physiology and Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland; Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Matti
authors.initials: M
authors.lastname: Poutanen
authors.affiliation: Center of Advanced European Studies and Research (Caesar), Minerva Research Group Molecular Physiology, Bonn, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wachten
authors.affiliation: Department of Physiology and Turku Center for Disease Modeling, Institute of Biomedicine, University of Turku, Turku, Finland. Electronic address: petra.sipila@utu.fi.
authors.forename: Petra
authors.initials: P
authors.lastname: Sipilä
mesh_terms: D020101:Acrosome Reaction; D000818:Animals; D004822:Epididymis / Q000502:physiology*; D005260:Female; D005298:Fertility; D055879:Gene Knock-In Techniques; D019426:Integrases / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013081:Sperm Motility / Q000235:genetics / Q000502:physiology; D013082:Sperm Tail / Q000502:physiology*; D013091:Spermatogenesis / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism / Q000502:physiology*; D015044:Zona Pellucida / Q000378:metabolism*; D023083:beta-Defensins / Q000235:genetics / Q000502:physiology*
chemical_list: C000613258:Defb41 protein, mouse; D023083:beta-Defensins; C045073:Cre recombinase; D019426:Integrases
keywords: Beta-defensin; Epididymis; Flagellar motility pattern; Sperm maturation; Sperm-oocyte binding; iCre knock-in