{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:49:05Z","timestamp":1790016545598,"version":"4.0.1"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Imatinib, the first-generation tyrosine kinase inhibitor (TKI), has been widely adopted as frontline therapy for chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). Growing evidence indicates potential gonadotoxic effects, raising concerns about its long-term impact on male fertility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This scoping review was undertaken to synthesize preclinical and clinical evidence on imatinib-induced reproductive toxicity in males, with emphasis on mechanisms, dose- and age-dependent susceptibility, and reversibility of testicular injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science following PRISMA-ScR guidelines. Twenty studies published between 2003 and 2025 were included.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Across animal and human studies, inhibition of Proto-oncogene c-KIT (c-KIT) and Platelet-Derived Growth Factor Receptor (PDGFR) signaling was consistently observed, leading to germ cell apoptosis, impaired spermatogonial proliferation, and disruption of the blood\u2013testis barrier (BTB). Dose-dependent reductions in testosterone and sperm density were documented, with partial recovery after drug discontinuation in several models. However, neonatal exposure was more often associated with persistent or irreversible testicular damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Imatinib exerts gonadotoxic effects through inhibition of c-KIT\/PDGFR signaling, disruption of the BTB, and dysregulation of the hypothalamic\u2013pituitary\u2013gonadal axis in a dose- and age-dependent manner. Although partial recovery is possible after withdrawal, neonatal and prepubertal exposures carry a high risk of irreversible impairment. These findings highlight the need for systematic fertility counseling and preservation in adolescent and reproductive-age males, in line with the 2025 European LeukemiaNet (ELN) recommendations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1811653","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T14:40:11Z","timestamp":1778769611000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["A scoping review of imatinib-induced testicular toxicity and male fertility impairment"],"prefix":"10.3389","volume":"17","author":[{"given":"Xia","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Gynaecology and Obstetrics, Inner Mongolia Baogang Hospital","place":["Baotou, Inner Mongolia, China"]},{"name":"Department of Obstetrics & Gynecology, Faculty of Medicine, Universiti Kebangsaan Malaysia","place":["Kuala Lumpur, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd Faizal","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, Faculty of Medicine, Universiti Kebangsaan Malaysia","place":["Kuala Lumpur, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd Helmy","family":"Mokhtar","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia","place":["Kuala Lumpur, Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XiaoYing","family":"He","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, Inner Mongolia University of Science and Technology","place":["Baotou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul Kadir","family":"Abdul Karim","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, Faculty of Medicine, 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