{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T11:14:50Z","timestamp":1791630890469,"version":"4.3.4"},"reference-count":36,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/RLF\/Re\u2010entry\/08\/2019"],"award-info":[{"award-number":["BT\/RLF\/Re\u2010entry\/08\/2019"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD107333\u201001 (SV)"],"award-info":[{"award-number":["HD107333\u201001 (SV)"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>\n                      Epididymal transit renders key competence to mammalian spermatozoa for fertilizing eggs. Generally, the two paralogs of glycogen synthase kinase 3, GSK3\u03b1 and GSK3\u03b2, functionally overlap except in testis and sperm. We showed that GSK3\u03b1 is essential for epididymal sperm maturation and fertilization. Male infertility is the only phenotype of mice with a global or testis\u2010specific knockout (KO) of\n                      <jats:italic>Gsk3\u03b1<\/jats:italic>\n                      . Their sperm maturation is impaired, and sperm cannot fertilize eggs in vitro and in vivo. This suggests that GSK3\u03b1 is a \u201cmale fertility kinase\u201d in mammals and that GSK3\u03b1\u2010selective inhibitor is a potential male contraceptive.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>A set of eight heterozygous Gsk3\u03b1(\u00b1) male mice received daily intraperitoneal injections of BRD0705, an isoform\u2010selective GSK3\u03b1 inhibitor, at 20\u00a0mg\/kg body weight for 1 week. Five vehicle\u2010treated and BRD0705\u2010treated mice were tested for in vivo fertility and the remaining mice were sacrificed; their caudal spermatozoa were examined for motility and biochemical properties.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The treated mice did not sire any pups while the control group sired 46 pups with a normal gestation period of 19\u201323 days. Continued fertility testing up to 6 weeks post\u2010treatment, showed that the treated mice regained fertility siring 56 pups, with 76 in the control group. Sperm motility was impaired, its abnormal morphology increased during epididymal transit, Adenosine triphosphate (ATP) levels were low, and tyrosine\u2010phosphorylation of hexokinase was absent: these phenotypes imitated those observed in\n                      <jats:italic>Gsk3\u03b1<\/jats:italic>\n                      KO mice. Tyrosine\n                      <jats:sup>279<\/jats:sup>\n                      \u2010phosphorylation of GSK3\u03b1 was reduced in sperm from the treated mice showing that the GSK3\u03b1 activity was inhibited. The altered sperm phenotypes returned to normal following recovery of fertility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Complete infertility resulted after 1 week of BRD0705\u2010treatment and fertility recovered after cessation of the treatment. Work is ongoing to determine the minimum dose and treatment time and the testing of new compounds with increased selectivity and inhibitory activity against GSK3\u03b1.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.13838","type":"journal-article","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T03:40:49Z","timestamp":1735875649000},"page":"2273-2281","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A non\u2010hormonal reversible contraceptive targeting GSK3\u03b1, a protein kinase, essential for epididymal sperm maturation"],"prefix":"10.1111","volume":"13","author":[{"given":"Mustfa","family":"Kabi","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Kent State University  Kent Ohio USA"},{"name":"Department of Biology Tabuk University  Tabuk Saudi 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