Oral Presentation ESA-SRB-APEG-NZSE 2022

New insights into ovarian development and function (#14)

Anthony D Bird 1 , Diana Vidovic 1 , Julia Kaburaki 1 , Pascal Bernard 1 , Elly Jarred 2 , Annie Novak 3 , Jeremy Le 1 , Joan Jorgensen 3 , Patrick Western 2 , Andrew J Pask 1 , Dagmar Wilhelm 1
  1. University of Melbourne, Melbourne
  2. Hudson Institute of Medical Research, Melbourne
  3. University of Wisconsin, Madison, USA

Normal development of the ovaries during embryogenesis is critical for their function and fertility of the adult female. Arguably, the most important signalling pathway for normal ovarian development is the canonical WNT signalling pathway activated by WNT4 and RSPO1. Recently, it has been shown that ATP6AP2 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 expressed in the developing gonads, led to our hypothesis that the multi-functional protein ATP6AP2 is important for ovarian development. To test this hypothesis, we generated mice with conditional deletion of Atp6ap2 in the somatic cells of foetal gonads using the Nr5a1-Cre line. Characterisation of this mouse line revealed that ATP6AP2 is important for the formation of primordial follicles, granulosa cell differentiation as well as granulosa cell and ultimately oocyte survival. In conclusion, our data demonstrate that these mice provide a novel experimental system to investigate the development of primordial follicle and the molecular pathways driving this process, which will be crucial for the understanding of physiological as well as pathological development and function of the ovary.