Research project Reproductive impairment from exposure to complex chemical mixture relevant to human and dog

The purpose of ReproManDo is to establish pet dogs as sentinels for human male reproduction within the concept of One Health, where human, animal and environmental challenges are addressed. Dogs have similar chemical exposure as humans due to shared home environment, a short time to reproductive maturity, and low genetic variances within breeds, which together argues for using dogs as models for human reproductive toxicity. In line with 3R principles ReproManDo demonstrates a non-experimental animal model of human relevance. 
This will be achieved by setting up two dog cell-assays using testes from neutered dogs and compare observed exposure outcome to human cell-assays. The cells that will be used are the Sertoli and Leydig cells, which are essential during the spermatogenesis as they provide structural and nutritional support, and produces hormones such as testosterone and anti-muellerian hormone (AMH). The cell assays will be exposed to human and dog relevant complex chemical mixtures at human blood realistic concentrations. Besides measurements of cell proliferation and biomarkers, we will do discovery and target metabolomics. The identified biomarkers will be explored in relevant adverse outcome pathways to strengthen the causal-effect relationship. By weight of evidence and their appropriateness as biomarkers in terms of predictivity of adverse effect and extrapolation across species will be illustrated.