Soluble adenylyl cyclase inhibition prevents human sperm functions essential for fertilization

Melanie Balbach, Lubna Ghanem, Thomas Rossetti, Navpreet Kaur, Carla Ritagliati, Jacob Ferreira, Dario Krapf, Lis C. Puga Molina, Celia Maria Santi, Jan Niklas Hansen, Dagmar Wachten, Makoto Fushimi, Peter T. Meinke, Jochen Buck, Lonny R. Levin

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Soluble adenylyl cyclase (sAC: ADCY10) has been genetically confirmed to be essential for male fertility in mice and humans. In mice, ex vivo studies of dormant, caudal epididymal sperm demonstrated that sAC is required for initiating capacitation and activating motility. We now use an improved sAC inhibitor, TDI-10229, for a comprehensive analysis of sAC function in mouse and human sperm. In contrast to caudal epididymal mouse sperm, human sperm are collected post-ejaculation, after sAC activity has already been stimulated. In addition to preventing the capacitation-induced stimulation of sAC and protein kinase A activities, tyrosine phosphorylation, alkalinization, beat frequency and acrosome reaction in dormant mouse sperm, sAC inhibitors interrupt each of these capacitation-induced changes in ejaculated human sperm. Furthermore, we show for the first time that sAC is required during acrosomal exocytosis in mouse and human sperm. These data define sAC inhibitors as candidates for non-hormonal, on-demand contraceptives suitable for delivery via intravaginal devices in women.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalMolecular human reproduction
Issue number9
StatePublished - Sep 1 2021


  • acrosome reaction
  • capacitation
  • contraception
  • cyclic AMP
  • sperm motility


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