ArticleProceedings of the National Academy of Sciences of the United States of America2013
Male contraception via simultaneous knockout of α1A-adrenoceptors and P2X1-purinoceptors in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 45 citations in OpenAlex.
- Efficacy of daily silodosin 8 mg as a potential reversible male contraceptive: A prospective placebo controlled study.International urology and nephrology · 2026Trial
- A prospective double-blind, randomized, placebo-controlled study to evaluate the efficacy of silodosin 8 mg as an on-demand, reversible, nonhormonal oral contraceptive for males: a pilot study.World journal of urology · 2020Trial
- Alpha-Adrenoceptor Blockade as a Novel Pathway Toward Non-Hormonal Male Contraception: A Mechanistic and Clinical Evidence Review.Journal of clinical medicine · 2026Review
- Expression of the P2X1 receptor remains in the type II spiral ganglion neurons in the mature rat cochlea.Purinergic signalling · 2026Article
- Structural basis of the multiple ligand binding mechanisms of the P2X1 receptor.Acta pharmacologica Sinica · 2025Article
- Regulation of nerve-evoked contractions of the murine vas deferens.Purinergic signalling · 2024Article
- Structural insights into the human P2X1 receptor and ligand interactions.Nature communications · 2024Article
- Adrenoceptors: Receptors, Ligands and Their Clinical Uses, Molecular Pharmacology and Assays.Handbook of experimental pharmacology · 2024Review
- The P2X1 receptor as a therapeutic target.Purinergic signalling · 2022Review
- P2 purinergic receptor dysregulation in urologic disease.Purinergic signalling · 2022Review
- Transcriptomics and Metabolomics Analysis of the Ovaries of High and Low Egg Production Chickens.Animals : an open access journal from MDPI · 2022Article
- The study of candidate genes in the improvement of egg production in ducks - a review.Poultry science · 2022Review
- Aqueous extracts of Urtica dioica (stinging nettle) leaf contain a P2-purinoceptor antagonist-Implications for male fertility.PloS one · 2022Article
- Roles for αThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2021Article
- Hypothalamic and ovarian transcriptome profiling reveals potential candidate genes in low and high egg production of white Muscovy ducks (Cairina moschata).Poultry science · 2021Article
- Synthesis of 2-phenyl-5,6,7,8-tetrahydroquinoxaline derivatives and screening for P2X1-purinoceptor antagonist activity in isolated preparations of rat vas deferens, for translation into a male contraceptive†.Biology of reproduction · 2020Article
- Updates in the function and regulation of αBritish journal of pharmacology · 2019Review
- Factors influencing biased agonism in recombinant cells expressing the human αBritish journal of pharmacology · 2017Article
- Purinergic Signalling: Therapeutic Developments.Frontiers in pharmacology · 2017Review
- Purinergic signaling in testes revealed.The Journal of general physiology · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Therapeutic targets for male contraception are associated with numerous problems due to their focus on disrupting spermatogenesis or hormonal mechanisms to produce dysfunctional sperm. Here we describe the dual genetic deletion of α1A-adrenergic G protein-coupled receptors (adrenoceptors) and P2X1-purinoceptor ligand gated ion channels in male mice, thereby blocking sympathetically mediated sperm transport through the vas deferens during the emission phase of ejaculation. This modification produced 100% infertility without effects on sexual behavior or function. Sperm taken from the cauda epididymides of double knockout mice were microscopically normal and motile. Furthermore, double knockout sperm were capable of producing normal offspring following intracytoplasmic sperm injection into wild-type ova and implantation of the fertilized eggs into foster mothers. Blood pressure and baroreflex function was reduced in double knockout mice, but no more than single knockout of α1A-adrenoceptors alone. These results suggest that this autonomic method of male contraception appears free of major physiological and behavioral side effects. In addition, they provide conclusive proof of concept that pharmacological antagonism of the P2X1-purinoceptor and α1A-adrenoceptor provides a safe and effective therapeutic target for a nonhormonal, readily reversible male contraceptive.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.