Summary

Infertility affects approximately one in twenty Australian men, and is a common experience for men with DSDs. The ATR-X syndrome, an X-linked recessive developmental disorder affecting males, belongs to a growing list of disorders of sex development (DSD) which affect 1% of all newborns. Clinical features alpha-thalassemia and skeletal and genital include mental retardation, abnormalities. The focus of our work is to investigate the role of ATRX in gonadal development to provide a better understanding of some underlying causes of male infertility.

Description

To understand the etiology of the testicular phenotype of the ATR-X syndrome, we have developed two mouse models. Similar to ATR-X syndrome patients, ubiquitous inactivation of Atrx in mice results in small testes and an absence of germ cells. Inactivation of Atrx specifically in the testicular Sertoli cells affects Sertoli cell survival, proliferation, and differentiation, resulting in reduced testicular growth.

We have discovered that the ATRX protein is an important regulator of androgen actions, as well as playing a key role in the survival of testicular cells.

These studies will improve our understanding of the role of ATRX in the testis and provide a clearer understanding of the molecular mechanisms of ATRX failure that lead to DSD and infertility.

Outcomes

• Establish the role of ATRX in gonadal development
• Identify testis-specific targets of ATRX

Funding

• National Health and Medical Research Council

Selected publications

• Bagheri-Fam, S., Argentaro, A., Svingen, T., Combes, A., Sinclair, A., Koopman, P. and Harley, V.R. (2011)Defective survival of proliferating Sertoli cells and androgen receptor function in a mouse model of the ATR-X syndrome. Human Molecular Genetics 20: 2213-2224