{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:50:47Z","timestamp":1780505447724,"version":"3.54.1"},"reference-count":44,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["grant number 1816\/13 to IBA"],"award-info":[{"award-number":["grant number 1816\/13 to IBA"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Med Oncol"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Testicular toxicity following chemotherapy is of increasing importance with the continuous improvement of survival rates. Gonadotropin-releasing hormone (GnRH) was suggested to protect testis against such toxicity; however, its suppressive quality and mechanism of action are still unclear. We examined whether and how pretreatment with GnRH antagonist protects against the testicular damage caused by chemotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Mature male mice were injected subcutaneously eight times in 2-day intervals with either saline or GnRH antagonist (Cetrotide; 1\u2009g\/mg), followed by an intraperitoneal injection with either saline or cyclophosphamide (CTX;100\u2009mg\/kg BW) and sacrificed 2\u2009weeks or 3\u2009months later. Testicular weight, epididymis weight, epididymal sperm count and sperm motility were measured. Serum anti-M\u00fcllerian hormone (AMH) was measured by enzyme-linked immunosorbent assay. Immunohistochemistry (Ki-67), immunofluorescence (PCNA, CD34), terminal transferase-mediated deoxyuridine 5-triphosphate nick-end labeling (TUNEL) and computerized analysis were performed to examine testicular proliferation, apoptosis and vascularization. Quantitative real-time PCR was used to assess the amount of spermatogonial reserve (Id4 and Gfra1 mRNAs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Pretreatment with GnRH antagonist transiently reduced testicular weight, epididymal weight, germinal proliferation and sperm count; it also abolished the permanent long-term effect of CTX on these parameters and prevented cyclophosphamide-induced testicular toxicity characterized by apoptosis and serum AMH increase and irreversible loss of spermatogonial reserve.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Our findings imply that pretreatment with GnRH antagonist temporarily reduces spermatogenesis and may be used as pretreatment for reducing chemotherapeutic testicular toxicity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17588359221113274","type":"journal-article","created":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T06:13:32Z","timestamp":1665123212000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Pretreatment with gonadotropin-releasing hormone antagonist protects against chemotherapy-induced testicular damage in mice"],"prefix":"10.1177","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5608-5910","authenticated-orcid":false,"given":"Mattan","family":"Levi","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"},{"name":"IVF Lab Director, IVF unit, Meir Medical Center, 59 Tchernichovsky st. Kfar Saba 4428163, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Shalgi","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irit","family":"Ben-Aharon","sequence":"additional","affiliation":[{"name":"Division of Oncology, Rambam Health Care Campus, Haifa, Israel"},{"name":"Rappaport Faculty of Medicine, Technion, Haifa, 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