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

Author

Listed:
  • Melanie Balbach

    (Weill Cornell Medicine)

  • Thomas Rossetti

    (Weill Cornell Medicine)

  • Jacob Ferreira

    (Weill Cornell Medicine)

  • Lubna Ghanem

    (Weill Cornell Medicine)

  • Carla Ritagliati

    (Weill Cornell Medicine)

  • Robert W. Myers

    (Tri-Institutional Therapeutics Discovery Institute)

  • David J. Huggins

    (Tri-Institutional Therapeutics Discovery Institute
    Weill Cornell Medicine)

  • Clemens Steegborn

    (University of Bayreuth)

  • Ileana C. Miranda

    (Memorial Sloan Kettering Cancer Center, and The Rockefeller University)

  • Peter T. Meinke

    (Weill Cornell Medicine
    Tri-Institutional Therapeutics Discovery Institute)

  • Jochen Buck

    (Weill Cornell Medicine)

  • Lonny R. Levin

    (Weill Cornell Medicine)

Abstract

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.

Suggested Citation

  • Melanie Balbach & Thomas Rossetti & Jacob Ferreira & Lubna Ghanem & Carla Ritagliati & Robert W. Myers & David J. Huggins & Clemens Steegborn & Ileana C. Miranda & Peter T. Meinke & Jochen Buck & Lonn, 2023. "On-demand male contraception via acute inhibition of soluble adenylyl cyclase," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36119-6
    DOI: 10.1038/s41467-023-36119-6
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    References listed on IDEAS

    as
    1. Zongliang Chang & Weibing Qin & Huili Zheng & Kathleen Schegg & Lu Han & Xiaohua Liu & Yue Wang & Zhuqing Wang & Hayden McSwiggin & Hongying Peng & Shuiqiao Yuan & Jiabao Wu & Yongxia Wang & Shenghui , 2021. "Triptonide is a reversible non-hormonal male contraceptive agent in mice and non-human primates," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
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