Mechanisms of foetal urogenital system development

Summary

We are studying the roles of particular genes in the formation of the foetal ovary, testis, and kidney. Information gained from these studies is integral to the development of better therapies and treatments for reproductive tract disease in humans.

Description

Our research interest is reproductive pathologies, including infertility, which are major health issues.

The causes of reproductive tract disease are not well-understood, but genetic abnormalities are one of the risk factors. However, discovering the underlying genetic causes of reproductive disease in humans is challenging: multiple genes interact to regulate reproductive health and fertility. The study of transgenic and knockout mice allows scientists to dissect out the roles of particular genes in the development and progression of diseases. Information gained from these studies is integral to the development of better therapies and treatments.

Our work focuses on the betaglycan gene, which encodes a cell-surface co-receptor that increases the sensitivity of cells to TGF-β and inhibin, two factors that regulate reproductive biology. We have previously deleted the betaglycan gene in mice, which resulted in a variety of birth defects, and roles for betaglycan in the growth and development of foetal organs were uncovered.

Our recent work focuses on discovering the role of this receptor in the foetal and adult urogenital system, in particular in the ovary, testis, and kidney. Defects in the development of these organs impact upon their health and functional capacity in adulthood, and a major goal of our research is to uncover the key developmental processes involved in determining adult reproductive capacity.

We use a combination of molecular and histochemical techniques to understand the regulatory processes that govern foetal development, including transcriptional profiling using high-throughput quantitative real time PCR, wholemount and section in situ hybridisation and immunocytochemistry, explant culture, and confocal microscopy.

Funding

National Health and Medical Research Council
Heart Foundation
Ian Potter Foundation

Outcomes

Demonstrated that the betaglycan gene is expressed differentially in the foetal, neonatal, and adult ovary and testis, suggesting multiple sex-specific roles for betaglycan in gonadal differentiation and maturation.
Established in betaglycan null mice that betaglycan is essential for the proper development of testis structure and for the proper functioning of the testis endocrine cells, the Leydig cells.

Selected Publications

Sarraj MA, Chua HK, Umbers A, Loveland KL, Findlay JK, and Stenvers KL. (2007) Differential expression of TGFBR3 (betaglycan) in mouse ovary and testis during gonadogenesis. Growth Factors. 25(5):334-45.

Stenvers, KL, Tursky, ML, Harder, KW, Kountouri, N, Amatayakul-Chantler, S, Grail, D, Small, C, Weinberg, RA, Sizeland, A and Zhu, HJ (2003) Defective heart and liver development and reduced TGF-β2 sensitivity in transforming growth factor-beta type III receptor-deficient embryos. Mol. Cell. Biol. 23(12): 4371-85