Poster Presentation ESA-SRB-APEG-NZSE 2022

The Role of the Renin Angiotensin System in Decidualisation and Throughout Pregnancy (#426)

Tess L Symington 1 2 3 , Sarah J Delforce 1 2 3 , Saije K Morosin 1 2 3 , Kirsty G Pringle 1 2 3
  1. School of Biomedical Science and Pharmacy, University of Newcastle, Newcastle, NSW, Australia
  2. School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia
  3. Mothers and Babies Research Program, Hunter Medical Research Institute, Newcastle, NSW, Australia

Transformation of the endometrium in pregnancy, or decidualisation, is key for embryo implantation and protecting the conceptus from the maternal immune system. It also provides initial nutrients to the embryo. All components of the Renin-Angiotensin System (RAS) are known to exist within the decidua at term, with downstream signalling cascades having the potential to sustain the decidua. In vitro studies have shown that the rate-limiting enzyme of the RAS, prorenin, is increased during decidualisation [1]. Thus, we aimed to describe the expression of the RAS in the decidua throughout gestation and investigate associations between its expression, its downstream targets, and markers of decidualisation.

Decidual tissue was collected from first trimester (n=12), second trimester (n=4) or term pregnancies in the absence of labour (n=12). qPCR was used to examine mRNA expression of decidualisation markers, RAS components and targets of RAS activation.

Expression of decidualisation markers prolactin and IGFBP-1 were highest in the second trimester (P=0.03 and P<0.01, respectively). Similarly, expression of angiotensinogen (AGT; P=0.005 vs. first trimester), prorenin receptor (ATP6AP2; P=0.016 vs first trimester and P=0.019 vs. term) and angiotensin converting enzyme (ACE; P=0.026 vs term) were also highest in the second trimester.  

When looking at downstream targets of the RAS that promote proliferation and vascularisation, both plasminogen activator inhibitor (PAI) and vascular endothelial growth factor (VEGF) show a significant increase over gestation (p=0.0039 and p=0.0034, respectively). Components of the sphingosine-phosphate pathway, SPHK1 and S1PR1, which have been shown to crosstalk with angiotensin II [2], and have roles in the maternal-fetal immune interface, are higher in the second trimester compared with the first (P<0.0001 and P=0.016, respectively).

These findings suggest that the RAS and its downstream targets may be contributing to the formation of the decidua or its function at critical stages in pregnancy.

 

  1. Lumbers, E.R., et al., Decidualisation of human endometrial stromal cells is associated with increased expression and secretion of prorenin. Reprod Biol Endocrinol, 2015. 13: p. 129.
  2. Alqarni, I., et al., Telmisartan and/or chlorogenic acid attenuates fructose-induced non-alcoholic fatty liver disease in rats: Implications of cross-talk between angiotensin, the sphingosine kinase/sphingoine-1-phosphate pathway, and TLR4 receptors. Biochem Pharmacol, 2019. 164: p. 252-262.