Comparative gonadotoxicity of the chemotherapy drugs cisplatin and carboplatin on prepubertal mouse gonads

Allen, C. M. , Lopes, F., Mitchell, R. T. and Spears, N. (2020) Comparative gonadotoxicity of the chemotherapy drugs cisplatin and carboplatin on prepubertal mouse gonads. Molecular Human Reproduction, 26(3), pp. 129-140. (doi: 10.1093/molehr/gaaa008) (PMID:31953538) (PMCID:PMC7103569)

Abstract

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.

• Item Type: Articles
• Additional Information: This work was funded by a Career Development PhD Scholarship and Children with Cancer UK grant #15-198. R.T.M.’s work was undertaken in the MRC Centre for Reproductive Health funded by MRC Centre Grant MR/N022556/1. CMA was supported by a Career Development PhD Scholarship in Biomedical Sciences funded by the Biomedical Sciences ZJU project.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Allen, Dr Caroline
• Authors: Allen, C. M., Lopes, F., Mitchell, R. T., and Spears, N.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Molecular Human Reproduction
• Publisher: Oxford University Press
• ISSN: 1360-9947
• ISSN (Online): 1460-2407
• Published Online: 18 January 2020
• Copyright Holders: Copyright © 2020 The Author(s)
• First Published: First published in Molecular Human Reproduction 26(3):129-140
• Publisher Policy: Reproduced under a Creative Commons license