Ovarian differentiation and sex reversal

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Defects of the internal and external genitalia are among the most common birth defects in babies (1 in 4,000 births) yet the aetiology in many cases is unclear. We will compare and contrast the mouse with a unique animal model the tammar wallaby to investigate the control of ovarian differentiation during early fetal and postnatal life. The gonad is unusual in that two completely different organs arise from the same precursor tissues, so that errors in development lead to intersexual phenotypes. Some intersexual conditions are the result of inappropriate exposure to hormones during fetal life, and others are due to spontaneous or inherited gene mutations. About 5-10% of ovarian cancer cases, that affect 1 in 8000 Australian women, are due to the inheritance of a faulty gene. We will use comparative analysis and an inducible sex reversal system to understand the way gene expression and hence tissue differentiation is altered between male and female during the formation of the ovary versus the testis. This will inform us about the causes and consequences of normal and abnormal sexual development, infertility and gonadal malignancies.