title: Male fertility depends on Ca²+ absorption by TRPV6 in epididymal epithelia.
abstract: TRPV6 [transient receptor potential vanilloid 6] is a calcium ion (Ca²+)-selective channel originally identified in the duodenal epithelium and in placenta; replacement of a negatively charged aspartate in the pore-forming region with an uncharged alanine (D541A) renders heterologously expressed TRPV6 channels nonfunctional. We found that male, but not female, mice homozygous for this mutation (Trpv6(D541A/D541A)) showed severely impaired fertility. The motility and fertilization capacity of sperm were markedly reduced, despite intact spermatogenesis. Trpv6 was expressed in epididymal epithelium where the protein was detected in the apical membrane, whereas it was not expressed in spermatozoa or the germinal epithelium. The Ca²+ concentration of the fluid in the cauda epididymis of Trpv6(D541A/D541A) males was 10 times higher than that of wild-type mice, which was accompanied by a seven- to eightfold decrease in Ca²+ absorption through the epididymal epithelium and was associated with reduced sperm viability. Thus, appropriate Ca²+ absorption and a consequent TRPV6-mediated decrease in the extracellular Ca²+ concentration toward the distal segments of the epididymal duct are essential for the acquisition of basic functions and the survival of spermatozoa.
authors.affiliation: Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, D-66421 Homburg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Weissgerber
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kriebs
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Tsvilovskyy
authors.forename: Jenny
authors.initials: J
authors.lastname: Olausson
authors.forename: Oliver
authors.initials: O
authors.lastname: Kretz
authors.forename: Christof
authors.initials: C
authors.lastname: Stoerger
authors.forename: Rudi
authors.initials: R
authors.lastname: Vennekens
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wissenbach
authors.forename: Ralf
authors.initials: R
authors.lastname: Middendorff
authors.forename: Veit
authors.initials: V
authors.lastname: Flockerzi
authors.forename: Marc
authors.initials: M
authors.lastname: Freichel
mesh_terms: D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D002522:Chlorocebus aethiops; D004822:Epididymis / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism*; D005260:Female; D005298:Fertility / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D050916:TRPV Cation Channels; C446923:Trpv6 protein, mouse; D002118:Calcium