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We have previously shown that imatinib has adverse effects on developing testis, and imatinib\u2010treated male patients have been reported to have reduced sperm counts. However, the cellular level effects of imatinib and dasatinib on adult male germ cells and germline stem cells (mGSCs) have not been thoroughly investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To analyze whether imatinib or dasatinib exposure ex vivo and in vitro is harmful to adult male rodent germ cells and mGSCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Seminiferous tubule segments of adult male mouse or rat were cultured in the presence or the absence of imatinib or dasatinib. Stage\u2010specific effects were monitored by <jats:sup>3<\/jats:sup>H\u2010thymidine incorporation assay (DNA synthesis), immunohistochemistry (cleaved Caspase\u20103; apoptosis), immunofluorescence (KI67, GFR\u03b11, STRA8, c\u2010KIT, LIN28A; proliferation and spermatogonial differentiation) and flow cytometry (Hoechst). Mouse mGSCs were exposed to imatinib and dasatinib to study proliferation, apoptosis, and differentiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Imatinib decreased stage\u2010specific DNA synthesis, and induced apoptosis in cultured rat seminiferous tubule segments. Imatinib also had an adverse effect on mGSC proliferation both in vitro and ex vivo, but did not induce cell death in cultured mGSCs. Imatinib did not impinge on induction of spermatogonial differentiation but suppressed c\u2010KIT expression in nascent differentiating spermatogonia, providing a plausible mechanism for its pro\u2010apoptotic function in spermatogenic cells. Clinically relevant doses of dasatinib did not induce apoptosis in seminiferous tubules but decreased mGSC colony growth in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Imatinib exposure ex vivo and in vitro impinges on male rodent germ cell proliferation and survival. The plausible mechanism in spermatogenic cells is the inhibition of SCF\/c\u2010KIT signaling, and reduced expression of c\u2010KIT. Dasatinib did not show significant adverse effects with clinical doses ex vivo but inhibited mGSC colony growth in vitro.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13777","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T10:20:17Z","timestamp":1729246817000},"page":"1575-1591","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Imatinib decreases germ cell survival and germline stem cell proliferation in rodent testis ex vivo and in vitro"],"prefix":"10.1111","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3640-1960","authenticated-orcid":false,"given":"Anna","family":"Eggert","sequence":"first","affiliation":[{"name":"Research Centre for Integrative Physiology and Pharmacology Institute of Biomedicine University of Turku Turku Finland"},{"name":"Tyks Acute Turku University Hospital Turku 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