Poster Presentation The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2017

The role of the prorenin/(P)RR interaction in fetal membrane integrity (#314)

Sarah J Delforce 1 , Eugenie R Lumbers 1 , Martha Lappas 2 , Tamas Zakar 1 , Kirsty G Pringle 1
  1. University Of Newcastle, New Lambton Heights, NSW, Australia
  2. University of Melbourne, Parkville, NSW, Australia

Preterm birth (PTB) is the single largest cause of death in infants and young children. 40-45% follow spontaneous labour with intact membranes and 25-30% are associated with preterm premature rupture of membranes (P-PROM). The primary cause of membrane weakness is unknown. In kidneys, the prorenin/(pro)renin receptor ((P)RR) interaction stimulates cell growth and the production of pro-fibrotic factors (including PAI-1, fibronectin and collagens), which maintains the extracellular matrix. However, the role of the prorenin/(P)RR interaction in regulating the integrity of the amnion is unknown. We postulate that prorenin, secreted by the decidua, acts upon amniotic (P)RR to stimulate pro-fibrotic factors and cell proliferation in order to maintain the amnion. With advancing gestation the prorenin/(P)RR interaction declines thus promoting membrane rupture.

Combined fetal membranes (amnion, chorion and decidua) from term and preterm non-laboring deliveries were obtained and REN (prorenin) and ATP6AP2 ((P)RR) mRNA expressions were determined by qRT-PCR. Both REN and ATP6AP2 ((P)RR) mRNA abundance was significantly decreased in term membranes compared with preterm membranes (P=0.0002 and 0.0142 respectively), which suggests that advancing gestation is associated with lower levels of expression of both REN and (P)RR. To validate the relationship between prorenin/(P)RR and membrane integrity primary amnion cells were isolated and transfected with 50 nM (P)RR siRNA. Following qRT-PCR validation for (P)RR knockdown, the effects of knockdown on downstream targets of the prorenin/(P)RR interaction and on measures of membrane integrity was determined. Inhibition of (P)RR was associated with decreased expression of Fibronectin, Collagen IV and TIMP1 mRNA; all of which play a major role in maintenance of the ECM. Thus the prorenin/(P)RR interaction is involved in maintaining amnion integrity and preventing preterm birth.