Project 4: Testis

Typical morphological changes of three-dimensional testicular cells culture (3D-TCS). Testicular cells were isolated from neonatal rats on Day 5, and cultured with ECM overlay as previously described (Yu et al, 2005). Morphological changes were monitored for a continuous 30 days. The main type of germ cells on Day in vitro 1 (DIV 1) is spermatogonia (SpG), and on DIV 10, pachytene spermatocytes (SpC-P) appeared as indicated by solid arrows. On DIV 14, we observed the production of spermatids (SpT) indicated by white arrows. The timeline of appearance of germ cells is consistent with the in vivo rat spermatogenesis.

The Testis Project uses 3-dimensional in vitro testicular co-cultures (3D-TCS) that have been shown to capture key processes of male reproductive development in order to evaluate the potential for metals and ENMs to alter these processes. We measure the ability of ENMs to alter cellular differentiation and tissue maturation with a focus on the roles of developmental timing and genetics in influencing compound susceptibility. We also explore the role of oxidative stress and inflammation pathways in mediating ENM induced perturbation of development. Finally, we use toxicokinetic and dynamic models to integrate in vitro our findings into our AOP framework.