Comparison of toxicogenomic responses to phthalate ester exposure in an organotypic testis co-culture model and responses observed in vivo.

We have developed a three-dimensional testicular co-culture system (3D-TCS) which mimics in vivo testes. In this study, transcriptomic responses to phthalate esters (PE's) were compared in the 3D-TCS with responses in rat testes in vivo. Microarray data from the 3D-TCS and from in vivo testes were used to compare changes in gene expression patterns after exposure to developmentally toxic (DTPE) or developmentally non-toxic (DNTPE) phthalate esters. DTPE treatments clustered separately from DNTPE treatments based on principle components analysis both in vitro and in vivo. Pathway analysis using GO-Elite software showed that terms relating to steroid metabolism or reproductive development were enriched both in vitro and in vivo after DTPE exposure. Processes such as cell cycle, cell proliferation and apoptosis were enriched for DTPE treatments in vitro, but not in vivo. Based on these analyses we concluded that transcriptomic responses in the 3D-TCS reflect key aspects of in vivo phthalate toxicity.