Poster Presentation Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society 2016

The role of the prorenin receptor ((P)RR) and soluble prorenin receptor (s(P)RR) in syncytialisation (#469)

Saije K Morosin 1 , Sarah J Delforce 1 , Samantha L Rodrigues 1 , Riazuddin Mohammed 1 , Guiying Nie 2 , Eugenie R Lumbers 1 , Kirsty G Pringle 1
  1. University of Newcastle, New Lambton Heights, NSW, Australia
  2. Hudson Institute of Medical Research, Melbourne, Victoria, Australia

Maintained by continuous fusion of placental cytotrophoblast cells, the syncytiotrophoblast is the major functional layer of the placenta that regulates the exchange of nutrients and wastes. Importantly, insufficient syncytialisation is associated with pregnancy complications such as preeclampsia and intrauterine growth restriction (IUGR). The placental renin-angiotensin system (RAS) is essential for appropriate placental development. The intrauterine RAS relies on the renin precursor, prorenin, binding to the prorenin receptor ((P)RR) to initiate the RAS cascade. As well as activating the RAS cascade, the prorenin/(P)RR pathway can induce intracellular signalling to promote cell growth and placental development. Recently, a soluble prorenin receptor (s(P)RR) has been discovered. s(P)RR release is formed from cleavage of the PRR by the pro-protein convertase enzyme, furin, which is also involved in syncytialisation of the cytotrophoblast.

We postulate that the (P)RR is critical for syncytialisation and that expression of s(P)RR, prorenin and furin are increased during syncytialisation. Furthermore furin causes s(P)RR release from the placenta during syncytialisation.

To examine the effects of syncytialisation on (P)RR, s(P)RR, prorenin and furin mRNA and protein levels in primary trophoblast cells isolated from healthy term placentae will be allowed to spontaneously syncytialise for up to 72 hours. We will also transfect primary trophoblasts with either a furin or (P)RR siRNA, and study their effects on syncytialisation, or in the case of furin knock down, its effects on s(P)RR release. Although the biological significance of the s(P)RR has yet to be determined, we think that it may be a biomarker for syncytialisation. Our research will provide better understanding of placental development and ultimately pregnancy complications including preeclampsia and IUGR.