PhD Projects on offer
Placento-fetal
hypoxia and preeclampsia
Supervisor: Dino A Giussani
Preeclampsia is the leading cause of maternal and fetal death in the UK, imposing an important problem in obstetric medicine today. The disease is characterised by maternal hypertension, protenuria and intrauterine growth retardation. Whilst delivery of the placenta resolves the adverse effects on the mother, fetal growth restriction is a major contributor to neonatal morbidity and mortality and it has been associated with increased risk of developing cardiovascular and metabolic disease in later life. Despite this, the physiological mechanisms underlying the disease are poorly understood, partly because the current overall consensus is that preeclampsia is multi-factorial in nature, involving vascular, genetic, immunological and/or environmental factors. What is generally accepted is that in preeclampsia there is inadequate invasion of the maternal uterine spiral arteries into the placental trophoblast. This results in poor placental perfusion and leads to placental and fetal hypoxia. Hypoxia is a potent stimulus for endothelial dysfunction and during pregnancy it promotes intrauterine growth retardation. Placento-fetal hypoxia may therefore provide a suitable stimulus linking the adverse effects of pre-eclampsia on the vascular physiology of the mother, placenta and unborn child. One mechanism via which placento-fetal hypoxia may affect several circulations is through the activation of oxidative stress. Generation of reactive oxygen species, such as the O2–, sequester NO reducing its bioavailability and thereby promoting an increase in vascular resistance. Interestingly, markers of oxidative stress are elevated in the placenta and circulation of affected women. In this PhD, using an integrative approach at the organismal, isolated organ, cellular and molecular levels, you will test the hypothesis that in pregnancy complicated by reduced placento-fetal oxygenation, hypoxia-induced oxidative stress is a predominant mechanism underlying preeclampsia. The hypothesis will be tested by investigating in rats the effects of hypoxic pregnancy with and without antioxidant treatment on placental and maternal circulatory indices of oxidative stress, on fetal growth, and on the vascular physiology of the mother, placenta and fetus.
Group website: http://www.trophoblast.cam.ac.uk/people/giussani.shtml
