Organotypic Modeling Platform for Adverse Outcome Pathways of Male Reproductive and Developmental Processes

Abstract

In recent decades male reproductive health and fertility problems have increased. Male reproductive dysfunction can be a result of exposure to chemicals during critical periods of testicular development. Studies have shown that testis development is one of the most sensitive developmental processes and often drives chemical risk assessment. The testis, however, is difficult to study and methods for assessing toxicity remain limited. This study addressed gaps in toxicity testing for this organ by building upon a co-culture method and framework for assessing toxicity outcomes in the developing testis. The aims of the study were to 1. develop a systems biology platform for integrating normal and adverse responses across testis development in rodents in vivo and in vitro; 2. leverage a previously developed co-culture method to quantify baseline characteristics of the mouse culture; and 3. use the mouse co-culture to evaluate effects of cadmium treatment during a critical window of susceptibility.