{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T05:03:35Z","timestamp":1781586215670,"version":"3.54.5"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"15","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV- 00371"],"award-info":[{"award-number":["INV- 00371"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-038185"],"award-info":[{"award-number":["INV-038185"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,4,14]]},"abstract":"<jats:p>Developing safe, reversible, and nonhormonal male contraceptives has been hindered by the lack of defined biological windows that can be transiently interrupted without compromising long-term fertility. Here, we tested whether meiotic prophase I can serve as such a window by pharmacologically inhibiting the testis-specific chromatin reader BRDT using the small-molecule bromodomain inhibitor (+)-JQ1 as proof-of-principle. Short-term JQ1 administration (3 wk) selectively disrupted the pachytene transcriptional program, depleted postmeiotic germ cells, and induced a reversible arrest in spermatogenesis. Upon drug withdrawal, prophase I cytological markers normalized within 6 wk, accompanied by restoration of testis architecture and germ-cell composition. Crossover metrics and transcriptional programs recovered more gradually, reaching full normalization by 30 wk alongside complete restoration of fertility and fecundity. These results demonstrate that meiotic prophase I can be transiently inhibited to suppress spermatogenesis reversibly without inducing lasting genomic or reproductive defects, defining a stage-specific framework for the rational design of nonhormonal male contraceptives.<\/jats:p>","DOI":"10.1073\/pnas.2517498123","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T16:16:01Z","timestamp":1775578561000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Meiotic prophase I disruption as a strategy for nonhormonal male contraception using small-molecule inhibitor JQ1"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9741-3845","authenticated-orcid":false,"given":"Stephanie","family":"Tanis","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Cornell Reproductive Sciences Center, College of Veterinary Medicine, Cornell 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Sciences Center, College of Veterinary Medicine, Cornell University","place":["Ithaca"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria de las Mercedes","family":"Carro","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Cornell Reproductive Sciences Center, College of Veterinary Medicine, Cornell University","place":["Ithaca"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha Jane","family":"Bonnett","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Cornell Reproductive Sciences Center, College of Veterinary Medicine, Cornell University","place":["Ithaca"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Cornell Reproductive Sciences Center, College of Veterinary Medicine, Cornell 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