Reduced vas deferens contraction and male infertility in mice lacking P2X1 receptors

K. Mulryan, D. P. Gitterman, C. J. Lewis, C. Vial, B. J. Leckie, A. L. Cobb, J. E. Brown, E. C. Conley, G. Buell, C. A. Pritchard and R. J. Evans ()
Additional contact information
K. Mulryan: Medical Sciences Building
D. P. Gitterman: Medical Sciences Building
C. J. Lewis: Medical Sciences Building
C. Vial: Medical Sciences Building
B. J. Leckie: Department of Medicine
A. L. Cobb: Transgenic Unit, Biomedical Services
J. E. Brown: Transgenic Unit, Biomedical Services
E. C. Conley: Department of Pathology and Centre for Mechanisms of Human Toxicity &
G. Buell: Glaxo-Wellcome Geneva Biomedical Research Institute
C. A. Pritchard: Department of Biochemistry, University of Leicester
R. J. Evans: Medical Sciences Building

Nature, 2000, vol. 403, issue 6765, 86-89

Abstract: Abstract P2X1 receptors for ATP are ligand-gated cation channels, present on many excitable cells including vas deferens smooth muscle cells1,2,3,4,5. A substantial component of the contractile response of the vas deferens to sympathetic nerve stimulation, which propels sperm into the ejaculate, is mediated through P2X receptors1. Here we show that male fertility is reduced by ∼90% in mice with a targeted deletion of the P2X1 receptor gene. Male mice copulate normally—reduced fertility results from a reduction of sperm in the ejaculate and not from sperm dysfunction. Female mice and heterozygote mice are unaffected. In P2X1-receptor-deficient mice, contraction of the vas deferens to sympathetic nerve stimulation is reduced by up to 60% and responses to P2X receptor agonists are abolished. These results show that P2X1 receptors are essential for normal male reproductive function and suggest that the development of selective P2X1 receptor antagonists may provide an effective non-hormonal male contraceptive pill. Also, agents that potentiate the actions of ATP at P2X1 receptors may be useful in the treatment of male infertility.

Date: 2000
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DOI: 10.1038/47495

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