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

• An in vitro model of spermatogenesis was evaluated with four testicular toxicants.
• In vitro findings correlated with in vivo pathology and known mechanisms.
• DNB targeted both Sertoli and germ cells within 2 weeks.
• MAA and BPA targeted Sertoli cells and blocked meiotic progression of germ cells.
• Lindane targeted Sertoli cells and caused death of meiotic spermatocytes in vitro.

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], [2] and [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.