title: Use of a rat ex-vivo testis culture method to assess toxicity of select known male reproductive toxicants.
abstract: 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.
authors.affiliation: Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, United States. Electronic address: goldsteinkm@lilly.com.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Goldstein
authors.affiliation: Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, United States.
authors.forename: David E
authors.initials: DE
authors.lastname: Seyler
authors.affiliation: Kallistem, Ecole Normale Supérieure de Lyon/IGFL, Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Durand
authors.affiliation: Inserm, U1208 Bron, France.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Perrard
authors.affiliation: Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, United States.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Baker
mesh_terms: D000085:Acetates / Q000633:toxicity; D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity; D002478:Cells, Cultured; D004136:Dinitrobenzenes / Q000633:toxicity; D005854:Germ Cells / Q000187:drug effects; D001556:Hexachlorocyclohexane / Q000633:toxicity; D008297:Male; D010636:Phenols / Q000633:toxicity; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012671:Seminiferous Tubules / Q000187:drug effects*; D012708:Sertoli Cells / Q000187:drug effects; D046509:Tissue Culture Techniques; D018675:Toxicity Tests / Q000379:methods*; D000098826:Bisphenol A Compounds
chemical_list: D000085:Acetates; D001559:Benzhydryl Compounds; D004136:Dinitrobenzenes; D001556:Hexachlorocyclohexane; D010636:Phenols; C017906:3-dinitrobenzene; C013598:methoxyacetic acid; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; Dinitrobenzene; In vitro model; Lindane; Methoxyacetic acid; Sertoli cell; Spermatogenesis; Testicular toxicity