Background
Preeclampsia (PE) is a common pregnancy complication characterised by
hypertension and proteinuria which is often the result of a poorly perfused
placenta. As hypertension is a feature of PE, the utero-placental renin
angiotensin system has been implicated in this disease. Remodelling of the
maternal spiral arteries which supply the placenta with maternal blood is an
essential step in early placentation. This remodelling process involves complex
interactions between a number of cell types including the spiral artery
endothelial cells and placental endovascular trophoblasts. Prorenin is a promoter
of endothelial cell angiogenesis and is involved in tissue remodelling.
Expression of prorenin and its receptor in response to the low oxygen tension
of the early intrauterine environment, and the effect of prorenin on
endovascular trophoblasts, is currently unknown.
Methods
HTR8/SVneo first trimester trophoblasts were cultured in 1%, 5% and 20% oxygen, 1% oxygen being that of the early placenta, 5% representing the lower end of intrauterine normoxia and 20% being standard culture conditions. RNA was extracted after 24h culture and expression of prorenin (REN) and prorenin receptor (ATP6AP2) were quantified by qPCR. Vasculogenesis in HTR8/SVneo treated with 200nM prorenin compared with untreated was measured using an in vitro tube formation assay and tube lengths quantified using ImageJ.
Results
ATP6AP2 was increased by 17.2% and 33.8% in 1% oxygen compared to 5% and 20%, respectively (p<0.01). REN expression was lower than that of ATP6AP2 and was not affected by oxygen. Preliminary results from the tube formation assay suggest that prorenin treatment does not affect vasculogenesis by HTR8/SVneo.
Conclusions
Increased ATP6AP2 expression in low oxygen suggests that the (pro)renin receptor may be involved in spiral artery remodelling early in pregnancy. This mechanism could be disrupted in PE, in which spiral artery remodelling is reduced leading to insufficient blood flow to the placenta.