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

P2X 1 receptors for ATP are ligand-gated cation channels, present on many excitable cells including vas deferens smooth muscle cells 1 , 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 receptors 1 . Here we show that male fertility is reduced by ∼90% in mice with a targeted deletion of the P2X 1 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 P2X 1 -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 P2X 1 receptors are essential for normal male reproductive function and suggest that the development of selective P2X 1 receptor antagonists may provide an effective non-hormonal male contraceptive pill. Also, agents that potentiate the actions of ATP at P2X 1 receptors may be useful in the treatment of male infertility.