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Pretreatment with gonadotropin-releasing hormone antagonist protects against chemotherapy-induced testicular damage in mice
| Content Provider | SAGE Publishing |
|---|---|
| Author | Levi, Mattan Shalgi, Ruth Ben-Aharon, Irit |
| Copyright Year | 2022 |
| Abstract | 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.Methods:Mature male mice were injected subcutaneously eight times in 2-day intervals with either saline or GnRH antagonist (Cetrotide; 1 g/mg), followed by an intraperitoneal injection with either saline or cyclophosphamide (CTX;100 mg/kg BW) and sacrificed 2 weeks or 3 months later. Testicular weight, epididymis weight, epididymal sperm count and sperm motility were measured. Serum anti-Müllerian 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).Results: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.Conclusions:Our findings imply that pretreatment with GnRH antagonist temporarily reduces spermatogenesis and may be used as pretreatment for reducing chemotherapeutic testicular toxicity. |
| Related Links | https://journals.sagepub.com/doi/pdf/10.1177/17588359221113274?download=true |
| ISSN | 17588359 |
| Volume Number | 14 |
| Journal | Therapeutic Advances in Medical Oncology (TAM) |
| e-ISSN | 17588359 |
| DOI | 10.1177/17588359221113274 |
| Language | English |
| Publisher | Sage Publications UK |
| Publisher Date | 2022-10-07 |
| Publisher Place | London |
| Access Restriction | Open |
| Rights Holder | © The Author(s), 2022 |
| Subject Keyword | spermatogonia fertility testis Gonadotropin-releasing hormone antagonist testicular toxicity |
| Content Type | Text |
| Resource Type | Article |
| Subject | Oncology |
