A systematic overview of the spermatotoxic and genotoxic effects of methotrexate, ganciclovir and mycophenolate mofetil
Autor: | Signe D. Justesen, Lars Pedersen, Erik Ernst, Agnete Larsen, Nicolai B. Jensen |
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Rok vydání: | 2021 |
Předmět: |
Male
Drug Ganciclovir COMET ASSAY ganciclovir media_common.quotation_subject CHEMOTHERAPEUTIC-AGENTS INDUCED TESTIS INJURY PERIPHERAL-BLOOD Pharmacology Mycophenolate medicine.disease_cause methotrexate INDUCED CYTOGENOTOXICITY paternal exposure 03 medical and health sciences semen quality 0302 clinical medicine systematic review MICRONUCLEUS TEST In vivo MULTIPLE TREATMENTS medicine Humans 030212 general & internal medicine OXIDATIVE STRESS media_common 030219 obstetrics & reproductive medicine business.industry genotoxicity mycophenolate mofetil Obstetrics and Gynecology General Medicine Mycophenolic Acid Spermatozoa INDUCED TESTICULAR DAMAGE Methotrexate sperm DNA damage MOUSE BONE-MARROW Animal studies business Spermatogenesis Immunosuppressive Agents Genotoxicity DNA Damage medicine.drug |
Zdroj: | Jensen, N B, Justesen, S D, Larsen, A, Ernst, E & Pedersen, L H 2021, ' A systematic overview of the spermatotoxic and genotoxic effects of methotrexate, ganciclovir and mycophenolate mofetil ', Acta Obstetricia et Gynecologica Scandinavica, vol. 100, no. 9, pp. 1557-1580 . https://doi.org/10.1111/aogs.14151 |
ISSN: | 1600-0412 0001-6349 |
DOI: | 10.1111/aogs.14151 |
Popis: | INTRODUCTION: Immunosuppressant drugs are increasingly being used in the reproductive years. Theoretically, such medications could affect fetal health either through changes in the sperm DNA or through fetal exposure caused by a presence in the seminal fluid. This systematic overview summarizes existing literature on the spermatotoxic and genotoxic potentials of methotrexate (MTX), a drug widely used to treat rheumatic and dermatologic diseases, and mycophenolate mofetil (MMF), which alone or supplemented with ganciclovir (GCV) may be crucial for the survival of organ transplants.MATERIAL AND METHODS: The systematic overview was performed in accordance with the PRISMA guidelines: A systematic literature search of the MEDLINE and Embase databases was done using a combination of relevant terms to search for studies on spermatotoxic or genotoxic changes related to treatment with MTX, GCV or MMF. The search was restricted to English language literature, and to in vivo animal studies (mammalian species) and clinical human studies.RESULTS: A total of 102 studies were identified, hereof 25 human and 77 animal studies. For MTX, human studies of immunosuppressive dosages show transient effect on sperm quality parameters, which return to reference values within 3 months. No human studies have investigated the sperm DNA damaging effect of MTX, but in other organs the genotoxic effects of immunosuppressive doses of MTX are fluctuating. In animals, immunosuppressive and cytotoxic doses of MTX adversely affect sperm quality parameters and show widespread genotoxic damages in various organs. Cytotoxic doses transiently change the DNA material in all cell stages of spermatogenesis in rodents. For GCV and MMF, data are limited and the results are indeterminate, for which reason spermatotoxic and genotoxic potentials cannot be excluded.CONCLUSIONS: Data from human and animal studies indicate transient spermatotoxic and genotoxic potentials of immunosuppressive and cytotoxic doses of MTX. There are a limited number of studies investigating GCV and MMF. |
Databáze: | OpenAIRE |
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