Use of a rat ex-vivo testis culture method to assess toxicity of select known male reproductive toxicants.

Due to the complex physiology of the testes, in vitro models have been largely unsuccessful at modeling testicular toxicity in vivo. We conducted a pilot study to evaluate the utility of the Durand ex vivo rat seminiferous tubule culture model [1-3] that supports spermatogenesis through meiosis II, including the formation of round spermatids. We used this system to evaluate the toxicity of four known testicular toxicants: 1,3-dinitrobenzene (DNB), 2-methoxyacetic acid (MAA), bisphenol A (BPA), and lindane over 21 days of culture. This organotypic culture system demonstrated the ability to successfully model in vivo testicular toxicity (Sertoli cell toxicity and disruption of meiosis) for all four compounds. These findings support the application of this system to study molecules and evaluate mechanisms of testicular toxicity.

In vitro testicular toxicity models: opportunities for advancement via biomedical engineering techniques.

To address the pressing need for better in vitro testicular toxicity models, a workshop sponsored by the International Life Sciences Institute (ILSI), the Health and Environmental Science Institute (HESI), and the Johns Hopkins Center for Alternatives to Animal Testing (CAAT), was held at the Mt. Washington Conference Center in Baltimore, MD, USA on October 26-27, 2011. At this workshop, experts in testis physiology, toxicology, and tissue engineering discussed approaches for creating improved in vitro environments that would be more conducive to maintaining spermatogenesis and steroidogenesis and could provide more predictive models for testicular toxicity testing. This workshop report is intended to provide scientists with a broad overview of relevant testicular toxicity literature and to suggest opportunities where bioengineering principles and techniques could be used to build improved in vitro testicular models for safety evaluation. Tissue engineering techniques could, conceivably, be immediately implemented to improve existing models. However, it is likely that in vitro testis models that use single or multiple cell types will be needed to address such endpoints as accurate prediction of chemically induced testicular toxicity in humans, elucidation of mechanisms of toxicity, and identification of possible biomarkers of testicular toxicity.