Innovative three-dimensional testicular Co-culture (Mini-Testis) model for reproductive toxicity testing: a pathway based High throughput (HT) and High Content Analysis (HCA)

Summary The need to identify chemicals for their potential to cause reproductive and developmental R D toxicity R D is a significant public health challenge for toxicologists In vivo testing for reproductive and developmental toxicity assessment uses a large number of animals yet these studies are criticized for their inefficiency The National Research Council NRC s report Toxicity Testing in the st Century envisioned that in vivo animal testing will eventually be replaced by a combination of in silico and in vitro approaches Therefore the need to identify in vitro systems for reproductive and developmental toxicity testing has grown ReproTOX has established an animal free testicular cell co culture system Mini Testis from testicular cell lines Both morphology and cellular biomarkers confirmed that this animal free D co culture model support in vitro spermatogenesis Our compound preliminary study revealed a stronger correlation of IC from the Mini Testis model with in vivo reproductive toxicity as compared to any single testicular cell culture model These initial results suggest that our Mini Testis model might be a valuable screening tool for reproductive toxicants and prioritizing chemicals for further testing The specific aims of this proposal therefore are to establish a toxicity based high throughput Mini Testis model for R D toxicity evaluation and develop an integrated pathway based high content HCA and high throughput HT screening assay in the Mini Testis model for R D toxicity evaluation The project outcome will be a cost efficient pathway based in vitro Mini Testis model for potential R D toxicity screening of chemicals Project narrative We will establish and develop a toxicity based high throughput screening HTS and pathway based high content HCA assay for R D toxicity evaluation This pathway based in vitro Mini Testis model will contribute significantly to public health by providing a cost efficient way to screen the chemicals for the potential R D toxicity