Research
Research summary
The aetiology of human obstetric complications, including preeclampsia and intrauterine growth restriction (IUGR), remains largely unclear. However, one of the most widely accepted theories is that shallow invasion of extravillous trophoblasts into the endometrium results in insufficient conversion of spiral arteries, and hence malperfusion of the placenta.
I am elucidating the placental molecular mechanisms and signal transduction pathways involved in IUGR and preeclampsia. Results indicate that in IUGR the induction of endoplasmic reticulum (ER) stress plays a crucial role via activation of protein synthesis inhibition and suppression of cell proliferation. These can be mimicked in vitro by hypoxia-reoxygenation of trophoblast-like cell lines. ER stress is greater in placentas from cases of IUGR complicated by preeclampsia, leading to the induction of apoptosis. This additional component may explain the increase in circulating placental debris that is thought to cause maternal endothelial cell activation. ER stress provides a novel explanation for the pathophysiology of these diseases.
I am a member of Prof Graham Burton's group.
Funding: Wellcome Trust
Publications
Yung HW, Cox M, Tissot van Patot M, Burton GJ, Evidence of endoplasmic reticulum stress and protein synthesis inhibition in the placenta of non-native women at high altitude. FASEB J. 2012 Jan 20. [Epub ahead of print]
Yung HW, Korolchuk S, Tolkovsky AM, Charnock-Jones DS, Burton GJ (2007). Endoplasmic reticulum stress exacerbates ischemia-reperfusion-induced apoptosis through attenuation of Akt protein synthesis in human choriocarcinoma cells. FASEB J. 3:872-84.
Cindrova-Davies T, Yung HW, Johns J, Spasic-Boskovic O, Korolchuk S, Jauniaux E, Burton GJ, Charnock-Jones DS (2007). Oxidative stress, gene expression, and protein changes induced in the human placenta during labor. Am J Pathol. 4:1168-79.
