The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Research Grants 2007-2008

3-D Sertoli cell/genocyte co-culture system: in vitro model for developmental testicular toxicity

Xiaozhong Yu, MD, PhD
University of Washington

The development of in vitro models that monitor and which can identify altered testis development would provide important alternatives to in vivo testing. Such methods would allow for the assessment of reproductive and developmental effects induced by environmental agents. These models would also provide information regarding mechanisms of toxicant action in the testis, leading to improvements in the interpretation of data obtained from in vivo systems and thus lead to significant refinement and reduction of in vivo animal use. In our previous research we demonstrated that our three-dimensional (3-D) Sertoli cell/gonocyte co-culture (SGC) system permitted the formation of a testicular-like multilayered architectural bio-structure that mimic in vivo characteristics of seminiferous tubules. We feel strongly that this novel in vitro SGC system will provide investigators with a simple, efficient, and highly reproducible alternative for the assessment of reproductive toxicity and the screening of testicular developmental toxicants. Thus, the purpose of this study is to further refine and characterize our in vitro 3-D SGC culture as a simple, efficient tool for screening testicular developmental toxicant by using a range of known in vivo male reproductive and developmental toxicants. This will be a systems based analysis using genomics and GO-quant technologies. We will also apply this 3-D SGC system to develop appropriate cell-based assays and biomarkers of susceptibility for testicular toxicity through the use of real-time nanotechnology biosensor assay methods. The establishment of a simple, efficient in vitro 3-D SGC culture model has the potential to greatly reduce the number of animals used through its ability to increase and refine the type of information obtained.