Virtual Presentation SRB Virtual Awards 2020

The Potential Role of The Renin Angiotensin System in Syncitialisation (#11)

Sonia Tamanna 1 2 , Saije K. Morosin 1 2 , Sarah J. Delforce 1 2 , Kym Rae 1 , Dirk Van Helden 2 , Eugenie R. Lumbers 1 2 , Kirsty G. Pringle 1 2
  1. Pregnancy and Reproduction Program, Hunter Medical Research Institute, University of Newcastle, Newcastle, New South Wales, Australia
  2. School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Newcastle, New South Wales, Australia

Components of the placental renin-angiotensin system (RAS; REN, AGT, AGTR1) are stimulated when primary trophoblasts are syncytialised1. To see what happens to other components of the placental RAS during syncytialisation, we measured angiotensin converting enzyme (ACE) which stimulates the Ang II/AT1R pathway, and other RAS enzymes (ACE2 and NEP) that control the opposing Ang-(1-7)/Mas pathway.

Two models of syncytialisation were used: primary human trophoblast cells which spontaneous syncytialise and a forskolin-induced human choriocarcinoma cell line. mRNA, protein levels and RAS enzyme activity were measured by qPCR, western blotting, ELISA and a quenched fluorescent substrate-based method.  

ACE mRNA levels were increased in primary trophoblasts during syncytialisation (P<0.001) whereas ACE2 and NEP mRNA levels were decreased (P<0.01). ACE, ACE2 and NEP protein levels and ACE2 activity in primary trophoblasts did not change.

Conversely, ACE mRNA and protein levels were decreased in BeWo cells after syncytialisation (p<0.05) and ACE2 mRNA and protein levels and activity were higher. NEP mRNA and protein levels were not affected.

Both primary trophoblast cells and BeWo cells secreted sACE, sACE2, sNEP. There were no changes in sACE2 levels but sACE and sNEP levels were reduced (P<0.001) following syncytialisation of primary trophoblasts.

The renin/Ang II/AT1R pathway is activated by syncytialisation1. In primary trophoblasts this is supported by the increase in ACE mRNA levels. The reduction in ACE2 mRNA levels suggests that metabolism of Ang II is reduced, which would enhance its effects the AT1R. These conclusions are supported by the molecular changes we measured but not by changes in protein levels.

BeWo cells stimulated with forskolin have been promoted as a model of syncytialisation but they don’t produce renin. hCG is a powerful stimulant of cytotrophoblast renin2. The failure of BeWo cells to mimic the findings in primary trophoblasts could be due to the lack of renin.

  1. Morosin SK, Delforce SJ, Lumbers ER, Pringle KG. The (pro)renin receptor (ATP6AP2) does not play a role in syncytialisation of term human primary trophoblast cells. Placenta. 2020;97:89-94.
  2. Downing GJ, Maulik D, Poisner AM. Human chorionic gonadotropin stimulates placental prorenin secretion: evidence for autocrine/paracrine regulation. The Journal of Clinical Endocrinology & Metabolism. 1996;81(3):1027-1030.