The role of the prorenin receptor in male and female fertility

Project Details

Infertility is a complex and devastating disease and although progress has been made, we still struggle to identify, diagnose and treat this condition. Infertility affects about one in six Australian couples of reproductive age. The inability to conceive has detrimental impacts on patients’ self-worth, mental health, financial status, and their relationships. It is estimated that about 40% of cases it is attributed to a male factor, 40% to a female factor and the remaining to a combination of both. While a genetic cause is often suspected, the molecular basis of infertility in humans remain poorly understood.

We have shown that loss of the prorenin receptor in mouse somatic cells of the gonads, testes and ovaries, results in both male and female infertility. The prorenin receptor is best known for its role in the renin-angiotensin system (RAS). However, recent research showed that it plays multiple roles independent of pro/renin binding. Using mouse as model system, this project characterizes its role in fertility and will therefore uncover critical mechanisms underlying testicular and ovarian development and disease.

Researchers

Dr Dan Bird, Post Doctoral Research Fellow

Mr Jeremy Le, Master student

Ms Ruchi Umargamwala, Honours student

Collaborators

A/Prof Patrick Western (Hudson Institute, Melbourne)

Dr Marie-Christine Chaboissier (University of Nice, France)

Prof Joan Jorgensen (University of Wisconsin, USA)

Dr Robin Hobbs (Hudson Institute, Melbourne)

Dr David Skerrett-Byrne and Prof Brett Nixon (University of Newcastle)

Prof Serge Nef (University of Geneva, Switzerland)

Funding

NHMRC New Ideas grant: “The prorenin receptor – a new candidate factor for ovarian disease.”

Research Publications

  • Nef S and Wilhelm D (2018). The impact of new technologies in our understanding of testis formation and function. Mol Cell Endocrinol 468, 1-2 doi: 10.1016/j.mce.2018.04.016
  • Fu A, Oberholtzer SM, Bagheri-Fam S, Rastetter RH, Holdreith C, Caceres VL, John SV, Shaw SA, Krentz KJ, Zhang X, Hui CC, Wilhelm D and Jorgensen J (2018). Dynamic expression patterns of Irx3 and Irx5 during germline cyst breakdown and primordial follicle formation promote follicle survival in mouse ovaries. PLoS Genetics 14, e1007488 doi: 10.1371/journal.pgen.1007488
  • De Cian MC, Pauper Eva, Bandiera R, Vidal VPI, Sacco S, GregoireEP, Chassot AA, Panzolini C, Wilhelm D, Pailhoux E, Youssef SA, de Bruin A, de Teerds K, Schedl A, Gillot I and Chaboissier MC (2016). Amplification of R-spondin 1 signaling induces granulosa cell fate defects and cancer in mouse adult ovary. Oncogene 36, 208-218

Research Group

Wilhelm laboratory: Gonad Development and Fertility



Faculty Research Themes

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 Physiology

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