Placental hypoxia inducible factor -1α & CHOP immuno-histochemical expression relative to maternal circulatory syncytiotrophoblast micro-vesicles in preeclamptic and normotensive pregnancies

Abstract

Objectives: Preeclampsia (PE) occurs as a result placental hypoxia-induced oxidative and endoplasmic reticulum stress, and is associated with the activation of hypoxia inducible factor-1α (HIF-1α) and apoptotic CHOP pathways with the consequential shedding of syncytiotrophoblast microvesicles which may be central in mediating the maternal systemic immune response. The aim of this study was to immune-localise and morphometrically analyse CHOP and HIF-1α within the placenta of normotensive and pre-eclamptic pregnancies and concomitantly quantify syncytiotrophoblast released microvesicles in maternal circulation.

Study design: Placental tissue and plasma were obtained from normotensive and pre-eclamptic pregnant women. The expression of CHOP and HIF-1α was analysed using immunohistochemistry. Isolation and size distribution of the circulating maternal microvesicles was determined using nanoparticle tracking analysis. The concentration of syncytiotrophoblast microvesicles was determined using the placental alkaline phosphatase ELISA.

Results: This study demonstrates a significant increase in immunohistochemical expression of HIF-1 α and CHOP in preeclampsia compared to the normotensive women (p<0.05). In keeping with this, a significant increase in the mean syncytiotrophoblast microvesicles concentration was observed in PE, compared to normotensives (p<0.05). A positive correlation between placental expression of CHOP and HIF-1α and STBMs was obtained.

Conclusion: This study demonstrates increased placental expression of HIF-1α and CHOP in preeclampsia compared to normotensive pregnancies which correlate to their increased syncytiotrophoblast microvesicles concentration in maternal circulation. These findings indicate that placental hypoxia and ER stress are interrelated contributory factors to the pathogenesis of PE and the consequential release of placental derived debris into the maternal circulation.

Keywords: CHOP; HIF-1α; Preeclampsia; Syncytiotrophoblast microvesicles.