Projects
21: Prenatal exposure to endocrine disrupting chemicals: Effects on the male urogenital system.
Mechanisms of endocrine disruption in mice.
The development of the male urogenital system in mammals is affected by exposure to (xeno)estrogens. Here, mouse functional genomics will be used to investigate how (xeno)estrogens affect sexual differentiation, cause urogenital malformations and decrease reproductive health.
Nef Serge, Centre Médical Universitaire, Genève
e-mail: serge.nef@medecine.unige.ch
Background
Clinical and epidemiological studies point towards a prominent increase in the incidence of male reproductive health problems over the past 50 years. These disorders, including cryptorchidism (undescended testes), hypospadias, declining semen quality and an increased incidence of testicular cancer, are classified under the term testicular dysgenesis syndrome (TDS). Recent reports suggest that the underlying causes of these male reproductive disorders are of foetal origin. This is corroborated by animal studies providing evidence that foetal exposure to endocrine disruptors affects sexual differentiation, causes urogenital malformations and decreases reproductive health. The rapid increase in male reproductive disorders since World War II suggests that environmental factors acting as endocrine disruptors may be the most plausible cause of TDS.
Aim
The aim of this project is to investigate, at the molecular level, the effects of estrogenic disruptors during male sexual differentiation.
Mice will be used as an animal model to study the toxicogenomic effects of foetal exposure to (xeno)estrogens on testicular gene expression and the molecular mechanism leading to estrogen-dependent cryptorchidism.
Significance
This project will lead to a better understanding of the molecular mechanisms underlying endocrine disruption as well as the physiological processes involved in sex-specific development. It will also provide a wealth of information indispensable in preventing and/or treating infertility problems caused by environmental and other factors. We expect to provide major insights into the aetiology and mechanisms of testicular dysgenesis syndromes and other male reproductive malformations such as cryptorchidia. Novel and powerful tools for the risk assessment of endocrine disruptors will be provided.