Comparative gonadotoxicity of the chemotherapy drugs cisplatin and carboplatin on prepubertal mouse gonads
| Autor: | Federica Lopes, Caroline M Allen, Norah Spears, Rod T. Mitchell |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
Embryology medicine.medical_treatment Pharmacology chemotherapy Carboplatin Mice chemistry.chemical_compound follicles 0302 clinical medicine Ovarian Follicle Sexual Maturation Original Research 0303 health sciences education.field_of_study Obstetrics and Gynecology Chemotherapy regimen 3. Good health medicine.anatomical_structure 030220 oncology & carcinogenesis Female medicine.drug fertility preservation Population gonadotoxicity Ovary testis Biology 03 medical and health sciences Organ Culture Techniques Genetics medicine Animals tissue culture Ovarian follicle education Antineoplastic Agents Alkylating Molecular Biology 030304 developmental biology Cisplatin Chemotherapy Granulosa Cells Sertoli Cells Cell Biology spermatogonia Reproductive Medicine chemistry Concomitant Developmental Biology |
| Zdroj: | Molecular Human Reproduction Allen, C, Lopes, F, Mitchell, R & Spears, N 2020, ' Comparative gonadotoxicity of the chemotherapy drugs cisplatin and carboplatin on prepubertal mouse gonads ', Molecular Human Reproduction . https://doi.org/10.1093/molehr/gaaa008 |
| ISSN: | 1460-2407 |
| Popis: | The treatment of childhood cancer with chemotherapy drugs can result in infertility in adulthood. Newer generations of drugs are developed to replace parent drugs, with the potential benefits of less toxic side effects. For platinum alkylating-like drugs, in contrast to the parent compound cisplatin, the newer-generation drug carboplatin is reported to have reduced toxicity in some respects, despite being administered at 5–15 times higher than the cisplatin dose. Whether carboplatin is also less toxic than cisplatin to the reproductive system is unknown. Here we compare the gonadotoxic impact of cisplatin and carboplatin on female and male mouse prepubertal gonads. In vitro cultured CD1 mouse ovaries or testis fragments were exposed to either cisplatin or carboplatin for 24 h on Day 2 of culture and analysed by Day 6. A dose response for each drug was determined for the ovary (0.5, 1 & 5 μg/ml cisplatin and 1, 5 & 10 μg/ml carboplatin) and the testis (0.01, 0.05 & 0.1 μg/ml cisplatin and 0.1, 0.5 & 1 μg/ml carboplatin). For the ovary, unhealthy follicles were evident from 1 μg/ml cisplatin (73% unhealthy, P = 0.001) and 5 μg/ml carboplatin (84% unhealthy, P = 0.001), with a concomitant reduction in follicle number (P = 0.001). For the testis, the proliferating germ cell population was significantly reduced from 0.05 μg/ml cisplatin (73% reduction, P = 0.001) and 0.5 μg/ml carboplatin (75% reduction, P = 0.001), with no significant impact on the Sertoli cell population. Overall, results from this in vitro animal model study indicate that, at patient equivalent concentrations, carboplatin is no less gonadotoxic than cisplatin. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|