Interplay of sex differentiation and metabolism

Project Details

Disorders of sex development (DSDs) include all congenital conditions in which the development of chromosomal, gonadal or anatomical sex is atypical. DSDs are more common than one might think, occurring in approximately 1 in 4,500 live birth. They represent a major paediatric concern and have profound psychological and reproductive consequences for the patient. Furthermore, patients with these disorders are often prone to testicular or ovarian cancer later in life, suggesting that mis-regulation of normal gonad differentiation is a key factor in understanding the origin of these tumours. Surprisingly, although many genes have been identified which play a role in these processes for almost 70% of cases we still do not know the underlying cause.

We have identified a new DSD candidate gene, HMGCS2, encoding the metabolic enzyme mitochondrial 3-hydroxy-3-methylglutaryl coenzyme A synthase 2 (HMGCS2), in a patient with gonadal dysgenesis and male-to-female sex reversal. This project will characterize the contribution of HMGCS2 to DSDs and will shed light on if and how diet can influence sex differentiation.


Dr Stefan Bagheri-Fam, postdoctoral researcher


A/Prof Serge Nef, University of Geneva, Switzerland
Prof Paul Thomas, University of Adelaide
Prof Andrew Sinclair, Murdoch Childrens Research Institute
Prof Matthew Watt, Monash University

Research Publications

  • Pitetti JL, Calvel P, Romero Y, Conne B, Truong V, Papaioannou MD, Schaad O, Docquier M, Herrera PL, Wilhelm D, Nef S. Insulin and IGF1 receptors are essential for XX and XY gonadal differentiation and adrenal development in mice. PLoS Genetics 2013; 9: e1003160
  • Wilhelm D, Hiramatsu R, Mizusaki H, Widjaja L, Combes AN, Kanai Y, Koopman P. SOX9 regulates prostaglandin D synthase gene transcription in vivo to ensure testis development. J Biol Chem 2007; 282: 10553-10560.
  • Wilhelm D, Martinson F, Bradford S, Wilson MJ, Combes A, Beverdam A, Bowles J, Mizusaki H, Koopman P. Sertoli cell differentiation is induced both cell-autonomously and through prostaglandin signalling to activate Sox9 during mammalian sex determination. Dev Biol 2005; 287: 111-124

Research Group

Wilhelm laboratory: Sex determination and disorders of sex development

Faculty Research Themes

Child Health

School Research Themes

Molecular Mechanisms of Disease

Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Anatomy and Neuroscience

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