Oral Presentation ESA-SRB-AOTA 2019

New insights into ovarian development and function  (#119)

Julia Kaburaki 1 , Pascal Bernard 2 , Stefan Bagheri-Fam 1 , Renata Phyland 1 , Jeremy Le 1 , JoAnne S Richards 3 , Andrew J Pask 2 , Dagmar Wilhelm 1
  1. Department of Anatomy & Neuroscience, University of Melbourne , Melbourne , VIC, Australia
  2. School of BioSciences, University of Melbourne, Melbourne, VIC, Australia
  3. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA

Normal development of the ovaries during embryogenesis is critical for their function and fertility of the adult female. The WNT4/RSPO1 signalling pathway is critical for normal ovarian development and function. Recently, it has been shown that the prorenin receptor (PRR), encoded by the Atp6ap2 gene, functions as a bridge between the WNT receptor LRP6 and the vacuolar H+-ATPase (V-ATPase). This interaction is crucial for canonical WNT signalling after binding of the ligand. These data, together with our observation that Atp6ap2 is highly expressed in the developing gonads, led to our hypothesis that PRR is important for ovarian development. In addition to the regulation of canonical WNT signalling PRR is best known for its role in the renin-angiotensin system. In addition, PRR is also important for other signalling pathways that play a role in ovarian development and/or function such as non-canonical WNT signalling and the ERK and p38-MAPK signalling pathways, demonstrating that PRR is a multi-functional protein. Hence, it is not surprising that complete loss of PRR in mouse, Drosophila, and zebrafish results in early embryonic lethality. To test our hypothesis that PRR is important for ovarian development we generated mice with conditional deletion of Atp6ap2 in the somatic cells of fetal gonads using the Nr5a1-Cre line. Here, we present the ovarian phenotype of these mice and show that PRR is important for granulosa cell differentiation and the cross-talk between granulosa cells and oocytes.