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


Editor's Summary

A Good Environment Is Crucial
Male infertility can result from decreased production of or functional deficits in sperm. Ca2+ signaling plays a crucial role in sperm function, and, here, Weissgerber et al. uncovered a role for the Ca2+-selective TRPV6 channel in regulating Ca2+ concentration in the lumen of the epididymis as well as sperm motility and survival. Sperm maturation—including the acquisition of motility—occurs in the epididymis, after their exit from the testis. Male transgenic mice bearing an inactive form of TRPV6 showed decreased fertility, and the motility, viability, and in vitro capacity to fertilize eggs of sperm isolated from their caudal epididymides were impaired. TRPV6 was present in epididymal epithelial cells but not in the sperm themselves, and the Ca2+ concentration in the lumens of the epididymides of transgenic mice was 10 times higher than in wild-type mice. Moreover, sperm exposed to comparable extracellular Ca2+ concentrations showed an increase in intracellular Ca2+ concentration. The authors thus conclude that TRPV6 channels function to decrease the Ca2+ concentration of the intraluminal fluid in the epididymis and propose that the impaired function and survival of sperm in the transgenic mice results from the disturbed microenvironment in the epididymal fluid.

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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Sperm parameters and epididymis function in transgenic rats overexpressing the Ca2+-binding protein regucalcin: a hidden role for Ca2+ in sperm maturation?.
S. Correia, P. F. Oliveira, P. M. Guerreiro, G. Lopes, M. G. Alves, A. V. M. Canario, J. E. Cavaco, and S. Socorro (2013)
Mol. Hum. Reprod. 19, 581-589
   Abstract »    Full Text »    PDF »
The in Vivo TRPV6 Protein Starts at a Non-AUG Triplet, Decoded as Methionine, Upstream of Canonical Initiation at AUG.
C. Fecher-Trost, U. Wissenbach, A. Beck, P. Schalkowsky, C. Stoerger, J. Doerr, A. Dembek, M. Simon-Thomas, A. Weber, P. Wollenberg, et al. (2013)
J. Biol. Chem. 288, 16629-16644
   Abstract »    Full Text »    PDF »
Interplay between Calmodulin and Phosphatidylinositol 4,5-Bisphosphate in Ca2+-induced Inactivation of Transient Receptor Potential Vanilloid 6 Channels.
C. Cao, E. Zakharian, I. Borbiro, and T. Rohacs (2013)
J. Biol. Chem. 288, 5278-5290
   Abstract »    Full Text »    PDF »
Functional TRPV6 channels are crucial for transepithelial Ca2+ absorption.
T. E. Woudenberg-Vrenken, A. L. Lameris, P. Weissgerber, J. Olausson, V. Flockerzi, R. J. M. Bindels, M. Freichel, and J. G. J. Hoenderop (2012)
Am J Physiol Gastrointest Liver Physiol 303, G879-G885
   Abstract »    Full Text »    PDF »
Vitamin D metabolism, sex hormones, and male reproductive function.
M. Blomberg Jensen (2012)
Reproduction 144, 135-152
   Abstract »    Full Text »    PDF »
Involvement of the transepithelial calcium transport disruption and the formation of epididymal stones in roosters.
A. G. Oliveira, D. J. Q. Aquino, G. A. B. Mahecha, and C. A. Oliveira (2012)
Reproduction 143, 835-844
   Abstract »    Full Text »    PDF »
Excision of Trpv6 Gene Leads to Severe Defects in Epididymal Ca2+ Absorption and Male Fertility Much Like Single D541A Pore Mutation.
P. Weissgerber, U. Kriebs, V. Tsvilovskyy, J. Olausson, O. Kretz, C. Stoerger, S. Mannebach, U. Wissenbach, R. Vennekens, R. Middendorff, et al. (2012)
J. Biol. Chem. 287, 17930-17941
   Abstract »    Full Text »    PDF »
The role of the TRPV6 channel in cancer.
V. Lehen'kyi, M. Raphael, and N. Prevarskaya (2012)
J. Physiol. 590, 1369-1376
   Abstract »    Full Text »    PDF »

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