On-demand male contraception via acute inhibition of soluble adenylyl cyclase.

Autor: Balbach M; Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA., Rossetti T; Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA., Ferreira J; Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA., Ghanem L; Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA., Ritagliati C; Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA., Myers RW; Tri-Institutional Therapeutics Discovery Institute, New York, NY, USA., Huggins DJ; Tri-Institutional Therapeutics Discovery Institute, New York, NY, USA.; Department of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA., Steegborn C; Department of Biochemistry, University of Bayreuth, Bayreuth, Germany., Miranda IC; Laboratory of Comparative Pathology, Weill Cornell Medicine, Memorial Sloan Kettering Cancer Center, and The Rockefeller University, New York, NY, USA., Meinke PT; Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA.; Tri-Institutional Therapeutics Discovery Institute, New York, NY, USA., Buck J; Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA. jobuck@med.cornell.edu., Levin LR; Department of Pharmacology, Weill Cornell Medicine, New York, NY, USA.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Feb 14; Vol. 14 (1), pp. 637. Date of Electronic Publication: 2023 Feb 14.
DOI: 10.1038/s41467-023-36119-6
Abstrakt: Nearly half of all pregnancies are unintended; thus, existing family planning options are inadequate. For men, the only choices are condoms and vasectomy, and most current efforts to develop new contraceptives for men impact sperm development, meaning that contraception requires months of continuous pretreatment. Here, we provide proof-of-concept for an innovative strategy for on-demand contraception, where a man would take a birth control pill shortly before sex, only as needed. Soluble adenylyl cyclase (sAC) is essential for sperm motility and maturation. We show a single dose of a safe, acutely-acting sAC inhibitor with long residence time renders male mice temporarily infertile. Mice exhibit normal mating behavior, and full fertility returns the next day. These studies define sAC inhibitors as leads for on-demand contraceptives for men, and they provide in vivo proof-of-concept for previously untested paradigms in contraception; on-demand contraception after just a single dose and pharmacological contraception for men.
(© 2023. The Author(s).)
Databáze: MEDLINE
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