Rationale for the research area
In several countries of the industrialized world, the incidence of male reproductive disorders such as urogenital malformations, testicular cancer and infertility is rising. Sperm counts in young adult men are declining and are lower than WHO normal values in some areas of Switzerland and other countries. In addition, Switzerland and Denmark have the highest incidences of testicular cancer in Europe, and incidences are rising (testicular cancer is now the commonest cancer in adolescent and young adult males.)
Many compounds have been proposed to induce testicular dysfunction and subsequent reproductive disorders by disrupting endocrine functions, including phthalates, organoplatinum compounds, organotins, heavy metals, vinclozolin and other pesticides. However, the mechanisms of toxicity and the underlying molecular targets are largely unknown. They need to be further characterized, to discover potential human biomarkers and establish mechanisms of action for human risk assessment.
Our overall goal is to investigate mechanisms of action in laboratory test systems in vitro and in vivo and to link them to epidemiological male reproductive data (male infertility, urogenital malformations, testicular cancer). This will enable us to identify human biomarkers of exposure and effect, and contribute to human risk assessment and early identification of new male reproductive toxicants.
The potential contribution of environmental chemicals to endocrine modulation in exposed humans and the subsequent impairment of fertility is one of the most intensely, and controversially, discussed questions in contemporary human toxicology research. This project aims to develop model systems for mechanistic studies with the subsequent goal of developing and validating biomarkers for human testicular disease; the work will support regulatory authorities by developing scientific expertise which will contribute to national and international efforts in addressing a potential human health problem of major public concern.