{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T03:09:01Z","timestamp":1782184141066,"version":"3.54.5"},"reference-count":46,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Male Contraceptive Initiative","award":["HD113015"],"award-info":[{"award-number":["HD113015"]}]},{"name":"Male Contraceptive Initiative","award":["HD111549"],"award-info":[{"award-number":["HD111549"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD113015"],"award-info":[{"award-number":["HD113015"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD111549"],"award-info":[{"award-number":["HD111549"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The second messenger cAMP plays multiple critical roles in the control of sperm functions essential for male fertility, including motility. The enzyme soluble adenylyl cyclase (sAC; ADCY10) was shown genetically and pharmacologically to be the essential source of cAMP mediating many of these functions. Male mice and men with genetic deletions of sAC are infertile, and their sperm are progressively immotile. Pharmacologically, delivery of potent and specific sAC inhibitors to male mice renders them temporarily infertile, and their sperm are similarly immotile. Here, we show that males from a second, independently derived mouse sAC knockout line are also infertile with progressively immotile sperm. We use these mouse models to determine optimal conditions for pharmacologically elevating intracellular cAMP to rescue the sAC null motility defect. We show that cell-permeable cAMP analogs, but not forskolin, rescue the motility defects of sAC deficient sperm, and we demonstrate that 8Br-cAMP is an efficient cAMP analog to rescue motility.<\/jats:p>","DOI":"10.3390\/ijms26041489","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T05:34:32Z","timestamp":1739252072000},"page":"1489","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Cyclic AMP Rescue of Motility in Sperm Devoid of Soluble Adenylyl Cyclase"],"prefix":"10.3390","volume":"26","author":[{"given":"Sylvia","family":"Ayoub","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1702-6974","authenticated-orcid":false,"given":"Natalia del R.","family":"Rivera Sanchez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Fischoeder","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Balbach","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5204-6356","authenticated-orcid":false,"given":"Lonny R.","family":"Levin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Buck","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Ritagliati","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Weill Cornell Medicine, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1093\/biolreprod\/5.3.336","article-title":"Stimulation and maintenance of ejaculated bovine spermatozoan respiration and motility by caffeine","volume":"5","author":"Garbers","year":"1971","journal-title":"Biol. 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