EGFL7 gene expression is regulated by hypoxia in trophoblast and altered in the plasma of patients with early preeclampsia

Abstract

INTRODUCTION:Preeclampsia is a severe complication of pregnancy, and likely arises from abnormal placental development in early pregnancy. Persistent placental hypoxia is thought to trigger the release of anti-angiogenic factors into the maternal circulation leading to widespread endothelial dysfunction. Epidermal growth factor-like domain 7 (EGFL7) is a secreted angiogenic factor that may play a key role in the disrupted angiogenesis seen in response to placental hypoxia that characterizes preeclampsia. METHODS:Primary trophoblasts were isolated and cultured in both normoxic and hypoxic conditions. Under hypoxia HIF1α was silenced and EGFL7 mRNA expression was assessed. EGFL7 mRNA expression was measured in placentas obtained from women with early (<34 weeks) and late onset preeclampsia; and in peripheral whole blood maternal samples from women with preeclampsia and gestation matched controls. EGFL7 plasma levels were assessed in plasma from women with preeclampsia, compared to gestation-matched controls. RESULTS:EGFL7 expression was significantly upregulated in primary human trophoblasts cultured in hypoxia (>2-fold, p < 0.0001), however this was not regulated via a HIF1α dependent manner. EGFL7 mRNA expression was not altered in placenta from women with early or late onset preeclampsia. Circulating EGFL7 protein levels were not different in women with severe preeclampsia. In contrast, EGFL7 mRNA expression was increased in maternal blood in women with early onset preeclampsia (∼1.6-fold, p < 0.05). DISCUSSION:EGFL7 mRNA expression is increased with hypoxia in human trophoblast and is increased in the maternal circulation in women with preeclampsia. Further studies aimed at understanding the role and regulation of EGLF7 in the pathophysiology of preeclampsia are required.