• PMID: 25160621
• Gene Name: P2RX1
• Condition: Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Male infertility

Nucleoside triphosphate diphosphohydrolase-1 ectonucleotidase is required for normal vas deferens contraction and male fertility through maintaining P2X1 receptor function

Kauffenstein G, Pelletier J, Lavoie EG, Kukulski F, Martín-Satué M, Dufresne SS, Frenette J, Ribas Fürstenau C, Sereda MJ, Toutain B, Henrion D, Sullivan R, Vial C, Sévigny J.

In this work, we report that Entpd1(-/-) mice, deficient for the ectonucleotidase nucleoside triphosphate diphosphohydrolase-1 (NTPDase1), produce smaller litters (27% reduction) compared with wild-type C57BL6 animals. This deficit is linked to reduced in vivo oocyte fertilization by Entpd1(-/-) males (61 ± 11% versus 88 ± 7% for Entpd1(+/+)). Normal epididymal sperm count, spermatozoa morphology, capacitation, and motility and reduced ejaculated sperm number (2.4 ± 0.5 versus 3.7 ± 0.4 million for Entpd1(+/+)) pointed to vas deferens dysfunction. NTPDase1 was localized by immunofluorescence in the tunica muscularis of the vas deferens. Its absence resulted in a major ATP hydrolysis deficiency, as observed in situ by histochemistry and in primary smooth muscle cell cultures. In vitro, Entpd1(-/-) vas deferens displayed an exacerbated contraction to ATP, a diminished response to its non-hydrolysable analog αβMeATP, and a reduced contraction to electrical field stimulation, suggesting altered P2X1 receptor function with a propensity to desensitize. This functional alteration was accompanied by a 3-fold decrease in P2X1 protein expression in Entpd1(-/-) vas deferens with no variation in mRNA levels. Accordingly, exogenous nucleotidase activity was required to fully preserve P2X1 receptor activation by ATP in vitro. Our study demonstrates that NTPDase1 is required to maintain normal P2X1 receptor functionality in the vas deferens and that its absence leads to impaired peristalsis, reduced spermatozoa concentration in the semen, and, eventually, reduced fertility. This suggests that alteration of NTPDase1 activity affects ejaculation efficacy and male fertility. This work may contribute to unveil a cause of infertility and open new therapeutic potentials. CI - © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. FAU - Kauffenstein, Gilles AU - Kauffenstein G AD - From the Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Québec G1V 0A6, Canada, the Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec G1V 4G2, Canada, the Unité mixte de recherche CNRS 6214 INSERM U1083, Université d'Angers, 49045 Angers, France, gilles.kauffenstein@gmail.com. FAU - Pelletier, Julie AU - Pelletier J AD - the Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec G1V 4G2, Canada. FAU - Lavoie, Elise G AU - Lavoie EG AD - From the Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Québec G1V 0A6, Canada, the Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec G1V 4G2, Canada. FAU - Kukulski, Filip AU - Kukulski F AD - From the Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Québec G1V 0A6, Canada, the Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec G1V 4G2, Canada. FAU - Martín-Satué, Mireia AU - Martín-Satué M AD - From the Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Québec G1V 0A6, Canada, the Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec G1V 4G2, Canada, the Departament de Patologia i Terapèutica Experimental, Facultat de Medicina, Universitat de Barcelona, 08907 Barcelona, Spain. FAU - Dufresne, Sébastien S AU - Dufresne SS AD - the Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec G1V 4G2, Canada, the Département de Réadaptation, Faculté de Médecine, Université Laval, Québec G1V 0A6, Canada. FAU - Frenette, Jérôme AU - Frenette J AD - the Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec G1V 4G2, Canada, the Département de Réadaptation, Faculté de Médecine, Université Laval, Québec G1V 0A6, Canada. FAU - Ribas Fürstenau, Cristina AU - Ribas Fürstenau C AD - From the Département de Microbiologie-Infectiologie et d'Immunologie, Faculté de Médecine, Université Laval, Québec G1V 0A6, Canada, the Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec G1V 4G2, Canada. FAU - Sereda, Michal J AU - Sereda MJ AD - the Department of Cell Physiology and Pharmacology, University of Leicester, Leicester LE1 9HN, United Kingdom, and. FAU - Toutain, Bertrand AU - Toutain B AD - the Unité mixte de recherche CNRS 6214 INSERM U1083, Université d'Angers, 49045 Angers, France. FAU - Henrion, Daniel AU - Henrion D AD - the Unité mixte de recherche CNRS 6214 INSERM U1083, Université d'Angers, 49045 Angers, France. FAU - Sullivan, Robert AU - Sullivan R AD - the Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec G1V 4G2, Canada, the Department of Obstetrics, Gynecology, and Reproduction, Faculté de Médecine, Université Laval, Québec G1V 0A6, Canada. FAU - Vial, Catherine AU - Vial C AD - the Department of Cell Physiology and Pharmacology, University of Leicester, Leicester LE1 9HN, United Kingdom, and.