Testis organ culture system capable of evaluating testicular toxicity

Abstract

ABSTRACTSuccessful treatment of pediatric cancers often results in long-term health complications, including potential effects on fertility. Therefore, assessing the male reproductive toxicity of anti-cancer drug treatments and the potential for recovery is of paramount importance. However,in vivoevaluations are time-intensive and require large numbers of animals. To overcome these constraints, we utilized an innovative organ culture system that supports long-term spermatogenesis by placing the testis tissue between a base agarose gel and a polydimethylsiloxane ceiling, effectively mirroring thein vivotesticular environment. The present study aimed to determine the efficacy of this organ culture system for accurately assessing testicular toxicity induced by cisplatin, using acrosin-green fluorescent protein (GFP) transgenic neonatal mouse testes. The testis fragments were treated with different concentrations of cisplatin-containing medium for 24 hours and incubated in fresh medium for up to 70 days. The changes in tissue volume and GFP fluorescence over time were evaluated to monitor the progression of spermatogenesis, in addition to the corresponding histopathology. Cisplatin treatment caused tissue volume shrinkage and reduced GFP fluorescence in a concentration-dependent manner. Recovery from testicular toxicity was also dependent on the concentration of cisplatin received. The results demonstrated that this novelin vitrosystem can be a faithful replacement for animal experiments to assess the testicular toxicity of anti-cancer drugs and their reversibility, providing a useful method for drug development.Short AbstractAssessing the male reproductive toxicity of anti-cancer drugs and the potential for recovery is of paramount importance, however,in vivoevaluations are time-intensive and require large numbers of animals. We utilized an innovative organ culture system that mirrors thein vivotesticular environment to determine its efficacy in accurately assessing testicular toxicity induced by cisplatin. The results demonstrate that this system can be a faithful replacement for animal experiments to assess the testicular toxicity of anti-cancer drugs and their reversibility.