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Sci. Signal., 3 May 2011
Vol. 4, Issue 171, p. ra27
[DOI: 10.1126/scisignal.2001791]

RESEARCH ARTICLES

Male Fertility Depends on Ca2+ Absorption by TRPV6 in Epididymal Epithelia

Petra Weissgerber1, Ulrich Kriebs1*, Volodymyr Tsvilovskyy1*, Jenny Olausson1*, Oliver Kretz2, Christof Stoerger1, Rudi Vennekens1, Ulrich Wissenbach1, Ralf Middendorff3, Veit Flockerzi1, and Marc Freichel1{dagger}

1 Experimentelle und Klinische Pharmakologie und Toxikologie, Universität des Saarlandes, D-66421 Homburg, Germany.
2 Institute of Anatomy and Cell Biology, Department of Neuroanatomy, University of Freiburg, 79104 Freiburg, Germany.
3 Institut für Anatomie und Zellbiologie, Justus Liebig Universität Gießen, Aulweg 123, D-35385 Gießen, Germany.

* These authors contributed equally to this work.

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 (Trpv6D541A/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 Trpv6D541A/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.

{dagger} To whom correspondence should be addressed. E-mail: marc.freichel{at}uks.eu

Citation: P. Weissgerber, U. Kriebs, V. Tsvilovskyy, J. Olausson, O. Kretz, C. Stoerger, R. Vennekens, U. Wissenbach, R. Middendorff, V. Flockerzi, M. Freichel, Male Fertility Depends on Ca2+ Absorption by TRPV6 in Epididymal Epithelia. Sci. Signal. 4, ra27 (2011).

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