How does chemotherapy treatment damage the prepubertal testis?

Allen, C. M. , Lopes, F., Mitchell, R. T. and Spears, N. (2018) How does chemotherapy treatment damage the prepubertal testis? Reproduction, 156(6), R209-R233. (doi: 10.1530/REP-18-0221) (PMID:30394705) (PMCID:PMC6347281)

Abstract

Chemotherapy treatment is a mainstay of anticancer regimens, significantly contributing to the recent increase in childhood cancer survival rates. Conventional cancer therapy targets not only malignant but also healthy cells resulting in side effects including infertility. For prepubertal boys, there are currently no fertility preservation strategies in use, although several potential methods are under investigation. Most of the current knowledge in relation to prepubertal gonadotoxicity has been deduced from adult studies; however, the prepubertal testis is relatively quiescent in comparison to the adult. This review provides an overview of research to date in humans and animals describing chemotherapy-induced prepubertal gonadotoxicity, focusing on direct gonadal damage. Testicular damage is dependent upon the agent, dosage, administration schedule and age/pubertal status at time of treatment. The chemotherapy agents investigated so far target the germ cell population activating apoptotic pathways and may also impair Sertoli cell function. Due to use of combined chemotherapy agents for patients, the impact of individual drugs is hard to define, however, use of in vivo and in vitro animal models can overcome this problem. Furthering our understanding of how chemotherapy agents target the prepubertal testis will provide clarity to patients on the gonadotoxicity of different drugs and aid in the development of cytoprotective agents.

• Item Type: Articles
• Additional Information: Funding by Children with Cancer UK (grant #15-198). R M’s work was undertaken in the MRC Centre for Reproductive Health funded by MRC Centre Grant MR/N022556/1, and C A was supported by 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: Reproduction
• Publisher: BioScientifica
• ISSN: 1470-1626
• ISSN (Online): 1741-7899
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Reproduction 156(6):R209-R233
• Publisher Policy: Reproduced under a Creative Commons license