Renin-angiotensin system (RAS) enzymes and placental trophoblast syncytialisation

Placental renin-angiotensin system (RAS) components; prorenin, angiotensinogen, and angiotensin (Ang) II type 1 receptor (AT₁R) are upregulated during syncytialisation. This study examined whether angiotensin-converting enzyme (ACE), ACE2 and neprilysin (NEP) are also altered during syncytialisation. Two in vitro models of syncytialisation were used: forskolin-treated BeWo cells and spontaneously syncytialising primary human trophoblast cells. Term placentae and primary trophoblasts had the highest levels of ACE, ACE2 and NEP mRNA. In primary trophoblasts, ACE mRNA levels significantly increased with syncytialisation, ACE2 and NEP mRNA levels decreased. ACE, ACE2 and NEP protein levels and ACE2 activity did not change. Syncytialisation of primary trophoblasts decreased soluble (s)ACE and sNEP but not sACE2 levels. In primary trophoblasts, the balance between the enzymes controlling the two opposing pathways of the RAS was maintained. These findings were unable to be reproduced in BeWo cells. Future studies exploring placental levels of these enzymes in pregnancies complicated by placental insufficiency are warranted.