Professor Graham Burton explores how new insights into the placenta offer a fresh approach to addressing chronic disease in adult life.
Professor Burton will be speaking at the event Building babies: the key to life-long health.
CSF: When did you first realise you wanted to be a scientist?
GB: I trained as a medical doctor but shortly after qualification I realised it was basic human biology that really fascinated me, and so I pursued a career in research. Although I no longer practice, my clinical training influenced the focus of my research, which aims to understand how complications of pregnancy arise and might be treated.
CSF: What drew you to focus on placental development and function?
GB: My first foray into placental research was a third-year project during my undergraduate degree. I was immediately captivated by the amazing biology that enables the fertilised egg to implant into the wall of the uterus and the placenta to develop to nurture and sustain it. The way the placenta brings the maternal and fetal circulations into close proximity, but does not allow them to mix, is just incredible. Also, the placenta very gently takes over maternal physiology during pregnancy, mobilising resources for exchange to the fetus, yet shields the fetus from her hormones and any toxins.
CSF: The placenta is one of the most important organs, but is not fully understood. Why is this?
GB: It is true that without the placenta none of us would be here, and for this reason over the centuries many societies have revered the organ, considering it a ‘guardian angel’ and conferring on it special rites. Scientifically, it has attracted less attention, and I think this is due in part to the fact that it is discarded at birth. Although the placenta is the largest of the fetal organs, once the baby is born its job is done and it is largely forgotten. Another reason is that the placenta is very hard to access while it is developing and functioning for obvious ethical reasons, and so there are very limited opportunities for experimentation. A final difficulty is that the placenta is more varied in its structure and function between different mammals than any other organ. Consequently, there is no perfect animal model that truly reflects the human situation.
CSF: How is research conducted? Can this pose risks?
GB: Much of the earlier research on the human was epidemiological and pathologically based, associating features of the placenta at delivery with the outcome of the pregnancy. The advent of ultrasound imaging first allowed placental development to be followed in vivo, and it is now possible to measure parameters such as the volume in 3-D accurately at various stages of gestation and the blood flow in the maternal and fetal circulations. This provides much greater insight into when things begin to go wrong, and how this affects development of the baby. More recently, magnetic resonance imaging (MRI) has been applied to the placenta, and this opens possibilities to assess oxygenation levels and obtain data relating to placental metabolism. At present MRI is only performed after about 20 weeks of pregnancy, but it is likely that it can be applied earlier once its safety has been assured. These imaging techniques can be supplemented by blood-based assays of placental hormones, or nowadays even fetal DNA circulating in the maternal blood provide an index of placental wellbeing. In terms of experimentation, we are restricted to working with samples from early pregnancy obtained from terminations of pregnancy, or placentas delivered at term. The latter can be connected to perfusion apparatus in the laboratory to investigate the transfer of molecules across the placenta, but the viability is limited.
CSF: Can you explain what developmental programming of adult health is?
GB: Organ systems are incredibly plastic as they develop, and programming has been defined as how ‘an early stimulus or insult, operating at a critical or sensitive period, results in a permanent or long-term change in the structure or function of the organism’. The importance of this for life-long health was highlighted by the work of David Barker and colleagues, who found that being born of low birth weight is associated with an increased risk of cardiovascular and a number of different diseases. Biologically, the number of cells that the developing heart or kidneys can grow will be determined by the supply of nutrients they receive in utero. Hence, if the mother is undernourished or the placenta does not function properly then the development of these critical organs is permanently compromised. They may function satisfactorily for the early years of life, but with aging and other secondary insults their function declines, resulting in heart disease, high blood pressure, diabetes and even certain cancers. Developmental programming provides a new way of looking at chronic diseases, and suggests we should place greater emphasis on ensuring optimal growth in utero in order to prevent their occurrence.
CSF: What can go wrong with the placenta and why?
GB: Unlike the situation in most mammals, the human placenta is highly invasive and the baby develops in the wall of the uterus and not in the cavity. This brings the placenta into a uniquely intimate relationship with the maternal tissues, and with her immune system. Like the fetus, the genes of the placenta are half from the mother and half from the father. The placenta is therefore to a certain extent foreign, and recent evidence from Cambridge indicates that immune interactions may underpin common complications of pregnancy that are almost restricted to humans.
CSF: Is there anything the mother can do to ensure optimum placental function?
GB: At present, the best advice is to ensure a healthy balanced diet leading up to and during pregnancy. Fresh vegetables and fruit are important as a source of anti-oxidants.
CSF: What are the latest developments?
GB: Advances in imaging, immunology, and ‘omics technologies are all providing new insights into placental development. The establishment of the Centre for Trophoblast Research and the Human Placenta Project mean that these are exciting times for placental research.