Goldstein Keith M, Seyler David E, Durand Philippe, Perrard Marie-Hélène, Baker Thomas K
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, United States.
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, United States.
Reprod Toxicol. 2016 Apr;60:92-103. doi: 10.1016/j.reprotox.2016.01.003. Epub 2016 Jan 21.
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.
由于睾丸生理结构复杂,体外模型在模拟体内睾丸毒性方面大多未获成功。我们开展了一项初步研究,以评估杜兰德离体大鼠生精小管培养模型[1 - 3]的效用,该模型支持精子发生至减数分裂II,包括圆形精子细胞的形成。我们利用这个系统评估了四种已知睾丸毒物的毒性:1,3 - 二硝基苯(DNB)、2 - 甲氧基乙酸(MAA)、双酚A(BPA)和林丹,培养时间为21天。这种器官型培养系统证明能够成功模拟所有四种化合物在体内的睾丸毒性(支持细胞毒性和减数分裂破坏)。这些发现支持将该系统应用于研究分子和评估睾丸毒性机制。