Current research into the micro-biology of the human placenta
by Katerina Georgopoulou on 26 May 2016
My current research into the micro-biology of the human placenta by Katerina Georgopoulou (MPhil, Medical Sciences, 2013 [Cantab] PhD student Biomedical Sciences [Imperial College, London])
The human placenta is a fascinating organ and I hope to explain here why, up to the present day, I have spent my scientific career working to develop a greater understanding of it.
Most people know that the human body has several vestigial body parts, organs that used to have a purpose but no longer do, such as the appendix or the wisdom teeth. The placenta, however, is the only organ that grows in adults from scratch and is self-disposable when it’s no longer needed. Even though it is the organ with the shortest life-span, without it we could have not lived. Twenty per cent of a pregnant woman’s blood circulates through the placenta every minute and, rather than being just a mediator between the mother and baby, the placenta actually has its own ‘’control panel’’, meaning that it produces hormones that regulate its metabolism and the growth of its vascular network, enabling it to extract the maximum amount of nutrients from the mother for the growth of the foetus. The placenta also responds to conditions such as maternal undernourishment, by getting bigger in order to accommodate more blood allowing more nutrients to be transferred to the growing foetus. In other situations, such as preeclampsia, which is a medical condition characterized by abnormally high maternal blood pressure in pregnancy, the placenta doesn’t grow properly and is responsible for the release of ‘’debris’’ into the maternal circulation, which probably act as a trigger for that condition.
Apart from being a multi-organ (working as a lung and a liver for the foetus), the placenta is also a semi-permeable membrane, allowing nutrients, oxygen, water and metabolites to move freely to the foetus, but preventing bacteria and viruses from entering. This selectivity for certain substances is not yet fully understood by the scientific community, so scientists have created a ‘’placenta on a chip’’, a device designed to model the placenta’s function to filter molecules. Apart from nutrients, the placenta also ensures the transportation of antibodies from the mother to the foetus, from the 20th week of pregnancy. This provides a carbon copy of almost all of the maternal antibodies, so that the foetus can have protection from infections during the first months of its life, before it develops its own immune system. It is worth mentioning, though, that not all maternal antibodies can travel to the foetus through the placenta, as some are just too big, so the foetus does not have full immunity. This is why some infections acquired during pregnancy can be hazardous for the foetus, such as HIV, toxoplasma and chickenpox.
Another fascinating aspect of the placenta is its cellular composition. It is made up of cells from two different organisms, the mother and the foetus. The latter inherits half of its DNA from the mother and the other half from the father. The maternal immune system hosts this semi-foreign organ for nine months without rejecting it, as would be the fate of any other foreign material. This unique phenomenon has been intensely investigated by immunologists, since a full understanding of the underlying mechanisms could help explain certain cases of placental abnormalities and advance current knowledge on organ transplantations in cases of organ failure.
My involvement with placenta biology started during my Master’s degree in the Department of Obstetrics and Gynaecology at the University of Cambridge. At that time, I was studying a growth hormone that is very important during the development of the foetus inside the womb. We had very strong evidence that the hormone is driving angiogenesis (the formation of new vessels) but we needed more scientific proof for that. Using mouse models that lack the hormone in specific cell types within the placenta, I managed to show that indeed the hormone is indispensable for the proliferation of a certain cell type called endothelial cells, which are the cells that make up the vessels, together with another specialized cell type called smooth muscle cell, which regulates how contracted or relaxed a vessel will be. I was by that time starting to get hooked on placenta biology and research in general, and that is when I decided to do a PhD in order to further study the molecules that dictate how the placenta is formed. Finding a place for my PhD was not easy, but I knew what I was looking for and this gave me a lot of confidence and determination.
During that time, I had the luck to meet a very gifted man, who gave me the opportunity to follow that dream. Professor Mark Johnson works as a clinician at Chelsea and Westminster Hospital in central London. He is leading a research group at Imperial College and he has also founded his own charity, Borne (http://www.borne.org.uk/) to raise awareness and funding for diseases in pregnancy and premature births. He eventually offered me a PhD position with full financial support from Borne in order to study preeclampsia, which occurs in 5% of all pregnancies in the United Kingdom, so it is quite common. Women who develop preeclampsia during their pregnancy present with abnormally high blood pressure and kidney dysfunction. Some of those women will develop seizures and have organ failure. This is the more severe form called eclampsia, and is detrimental both for the mother and the fetus. There is currently no known cure for the disease, and the only way to save the mother and potentially the baby is delivery of the placenta. However, in most cases this means that the baby is born prematurely and is at high risk of infections, pulmonary edema and cardiovascular disease in later life.
Part of my PhD project is to analyze human placentas and DNA from mothers who developed preeclampsia during their pregnancy, as well as the fathers and the babies. I am looking at specific ‘’footprints’’ in the genes involved in the nitric oxide pathway in order to identify some link between them and the disease. This might function as a prognostic tool for this disease in the future. Since the embryo and its placenta are made up of cells with maternal and paternal DNA, we have hypothesized that paternal genes inherited by the fetus could cause the disease in the mother. If this proves true, then the process of picking a future father for your children could be even more laborious! I have also generated some models of pregnancy in mice where these genes have been deleted from the mouse genome. So far, I have found that these mice develop hypertension during their pregnancy and they also have high levels of some factors in their blood circulation, which have been detected in women with preeclampsia too. New technologies have enabled me to measure continuous blood pressure in these animals during the whole period of their pregnancy and also to get a very close look at the embryos and their placentas, while they are in womb by using Doppler ultrasonography, something similar to ultrasound scanning that we use in hospitals. My ultimate goal is to identify a diagnostic biomarker, a molecule which can alert the doctors to possible preeclampsia before it manifests and in this way to contribute to the clinical management and a better outcome for women.
I feel that this important field of research will continue to improve outcomes for susceptible mothers and babies. I also hope that by writing this article I may raise the awareness of pregnant women, who may wish to donate their placenta for research, so that more lives can be saved in the future.