Graduate Research: Understanding Complicated Pregnancies

by Katerina Georgopoulou on 14 August 2014

I originally graduated from the University of Crete, with a degree in Molecular Cell Biology. During my final year as an undergraduate, I carried out an internship at the Cancer Research UK Cambridge Institute, and returned to the city to study for an MPhil in Medical Sciences under the supervision of Dr. Miguel Constância in the Department of Obstetrics and Gynaecology, School of Clinical Medicine. I was also a member of the Centre for Trophoblast Research, where I received part of my academic training. I am about to begin a PhD in the field of cardiovascular research and pregnancy disorders at Imperial College London.

My MPhil project focused on IGF2 (Insulin-Like Growth Factor 2), a protein hormone similar to insulin that is present in the placenta and the embryo during pregnancy. This growth factor has been well characterised in mouse and human pregnancy and there is extensive literature describing its role in different aspects of embryonic and placental growth, including the development of foetal pancreatic cells. By using a combination of genetically engineered mouse models in which IGF2 was absent from either the embryo, or the placenta, or both, I discovered that IGF2 is also critical for the growth of the so-called vascular tree of the placenta (made up of arteries, veins and small capillaries).

The embryos I studied are smaller than those of normal mice and their placentas develop a smaller, less dense vascular network. The vascular tree of the placenta is crucial during pregnancy, as it is the place where nutrients are transferred and gases exchanged between the circulatory system of the mother and that of the foetus. It has been shown that the placentas of embryos that are born growth-restricted have less developed blood vessels. Interestingly, in many cases of pre-eclampsia (the most prevalent pregnancy-related disorder, occurring in 3%-5% of pregnancies), the underlying pathology is identified as angiogenic dysfunction: an abnormality or impairment in the formation of new blood vessels. Studying vascular growth in the placenta, alongside placenta development more generally, is key to improving our understanding of pre-eclampsia and other so far unknown causes of pregnancy complications. Apart from the immediate threat posed to the mother and the embryo during a pre-eclamptic pregnancy, the baby is also at higher risk of developing cardiovascular diseases as well as diabetes during adulthood. This indicates the importance of the placenta, and the extent to which the life of the baby is  predetermined before it comes out of the womb.

Within the Department of Obstetrics and Gynaecology, there is an ongoing large-scale study led by Professor Gordon Smith, for which placentas from over 2400 women with various pregnancy disorders have been collected and will be analysed for the identification of specific biochemical markers that enable the prediction of a high-risk pregnancy. It is hoped the study will help clinicians screen for stillbirth, which can result from pre-eclampsia.

Being part of the Department, and the University of Cambridge, has been an invaluable experience for me, because I have had the chance to work with people eager to share their expertise and love for research. Among them is my supervisor Dr. Miguel Constância, who gave me the opportunity to be part of his team and to contribute to this highly exciting field. I am also grateful to my College, Lucy Cavendish, for the amazing academic environment it provided for me and the life-time friends that I made there during my studies. During my journey, I encountered many challenges, including tight schedules for my experiments, time management and difficulty striking a balance between lab and College/social life, and I would particularly like to thank my College Tutor, Dr. Susan Jackson, for her mentoring and her advice.