{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:09:56Z","timestamp":1790086196025,"version":"4.0.1"},"reference-count":72,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":225,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Department of Biotechnology, Ministry of Science and Technology","award":["BT\/RLF\/Re-entry\/08\/2019"],"award-info":[{"award-number":["BT\/RLF\/Re-entry\/08\/2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Glycogen synthase kinase 3 alpha (GSK3\u03b1) has emerged as a prospective target to develop male contraceptives. Global or testis-specific loss of GSK3\u03b1, but not GSK3\u03b2, results in male infertility. Previous studies demonstrated that the GSK3\u03b1-selective inhibitor BRD0705 induces reversible infertility in heterozygous mice. Here, we show that BRD0705 induces similar infertility in wild-type male mice. Fertility outcomes remain largely unaltered following superovulation in female mice mated with BRD0705-treated males. Further, no evidence of foetal resorption was observed in these females. Sperm count in treated mice was not altered; however, morphological defects appeared during their passage through the epididymis. The GSK3\u03b1 inhibitor affected pathways related to the enzyme\u2019s catalytic activity in epididymal sperm. Phosphoproteomic analysis of sperm from inhibitor-treated mice showed that phosphorylation of over 50 proteins involved in motility, metabolism, and fertility, among others, was significantly altered. Among the highly hypophosphorylated proteins, four are likely substrates of GSK3 (viz., AKAP4, NT5C1B, SPATA18, and TRA2B). Analysis of the seminiferous tubules of BRD0705-treated mice showed normal spermatogenesis, suggesting that the drug did not affect developing spermatogenic cells. However, in vitro exposure of post-meiotic germ cells demonstrated their susceptibility to this inhibitor. BRD0705, therefore, shows only a non-genomic effect at the post-translational level. These findings support GSK3\u03b1 inhibition via BRD0705 as a non-hormonal, on-demand, and reversible male contraceptive strategy.<\/jats:p>","DOI":"10.1093\/molehr\/gaag049","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T05:49:59Z","timestamp":1786686599000},"source":"Crossref","is-referenced-by-count":0,"title":["Physiological basis of contraceptive function of a GSK3\u03b1-selective inhibitor, manifested during epididymal sperm maturation"],"prefix":"10.1093","volume":"32","author":[{"given":"Aditi","family":"Khamamkar","sequence":"first","affiliation":[{"name":"Department of Biotherapeutics Research, Manipal Academy of Higher Education , Manipal, Karnataka,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rounak","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Biotherapeutics Research, Manipal Academy of Higher Education , Manipal, Karnataka,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhanu Anneyplar","family":"Shivakumar","sequence":"additional","affiliation":[{"name":"Department of Biotherapeutics Research, Manipal Academy of Higher Education , Manipal, Karnataka,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Choudhari","sequence":"additional","affiliation":[{"name":"Department of Biotherapeutics Research, Manipal Academy of Higher Education , Manipal, Karnataka,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Dutta","sequence":"additional","affiliation":[{"name":"Department of Reproductive Science, Kasturba Medical College of Manipal, Manipal Academy of Higher Education , Manipal, Karnataka,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"We\u00efwer","sequence":"additional","affiliation":[{"name":"Centre for the Development of Therapeutics, Broad Institute , Cambridge, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2897-4697","authenticated-orcid":false,"given":"Satish Kumar","family":"Adiga","sequence":"additional","affiliation":[{"name":"Department of Reproductive Science, Kasturba Medical College of Manipal, Manipal Academy of Higher Education , Manipal, Karnataka,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivasan","family":"Vijayaraghavan","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Kent State University , Kent, OH,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1799-5270","authenticated-orcid":false,"given":"Souvik","family":"Dey","sequence":"additional","affiliation":[{"name":"Department of Biotherapeutics Research, Manipal Academy of Higher Education , Manipal, 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