̽��ֱ�� of Cambridge - pre-eclampsia

Surviving birth

lw355 — Thu, 10 Dec 2020 09:00:28 +0000

Researchers at one of the busiest maternity hospitals in the world aim to help more women survive complications giving birth.

Smoking and pre-eclampsia may cause fertility problems for offspring, study suggests

cjb250 — Fri, 29 Mar 2019 08:00:00 +0000

̽��ֱ��research, led by scientists at the ̽��ֱ�� of Cambridge, found that exposing fetuses to chronic hypoxia (low oxygen levels) during development led to them having advanced ageing of the ovaries and fewer eggs available.

Hypoxia in the womb can be caused by a number of factors, including smoking, pre-eclampsia, maternal obesity, and living at high altitude. ̽��ֱ��condition is already known to have potential long term effects on the health of offspring, including increased risk of heart disease. However, this study, published in ̽��ֱ��FASEB Journal, is the first time it has been shown to affect fertility.

To investigate the effects of hypoxia, researchers from the Metabolic Research Laboratories at the ̽��ֱ�� of Cambridge placed pregnant female rats in reduced levels of oxygen (13%, compared to the standard 21% found in air) from day six to day 20 of their pregnancy. They then examined the reproductive tract of their female pups at age four months.

Rats are a useful model for studying pregnancy. As a mammal, their bodies and underlying biology share some key similarities with those of humans. However, their gestation period and lifecycles are much shorter than those of humans, making them an ideal animal model in which to study pregnancy and fetal development.

When the team examined the pups, they found a decrease in the number of ovarian follicles in the reproductive tract. Females are born with fixed numbers of follicles, each with the potential of developing into an egg. In humans, women usually expend all their eggs around the age of fifty, at which point they will enter menopause.

̽��ֱ��researchers also looked at telomere length in the pups’ ovarian tissue. Telomeres are found at the end of chromosomes and prevent the chromosome from deteriorating – they are often compared to the plastic that seals the end of shoe laces. As we age, telomeres become shorter and shorter, and hence their length can be used as a proxy to measure ageing. ̽��ֱ��researchers found that telomeres in the ovarian tissue of pups exposed to hypoxia were shorter than in unexposed pups.

“It’s as if low levels of oxygen caused the female’s ovarian tissue to age faster,” says Dr Catherine Aiken from the ̽��ֱ�� of Cambridge. “Biologically, the tissue appears older and the female would run out of eggs – in other words, become infertile – at a younger age.”

Although the research was carried out in rats, Dr Aiken says there is every reason to expect that the findings could be translated to humans as previous studies looking at hypoxia during pregnancy in relation to other conditions such as heart disease have been shown to be relevant in humans.

While women are recommended not to smoke during pregnancy, other causes of hypoxia, such as pre-eclampsia and living in a high altitude, are beyond their control. However, says Dr Aiken, the findings of her team’s research may prove helpful to women who were exposed to low levels of oxygen during their mother’s pregnancy.

“Now that we’ve seen a link between hypoxia and fertility problems in rats, we know what to look for in women,” she says. “If the same turns out to be true for them, then women at risk will be able to take action: by having children earlier in life or looking to assisted reproduction, such as IVF, there should be no reason why these women cannot have children.”

Dr Aiken is also involved in research looking at whether anti-oxidant medication may help undo any damage caused by hypoxia.

Reference
Aiken, CE et al. Chronic gestational hypoxia accelerates ovarian ageing and lowers ovarian reserve in next-generation adult rats. FASEB; 27 March 2019; DOI: 10.1096/fj.201802772R

Low levels of oxygen in the womb – which can be caused by smoking or conditions such as pre-eclampsia – may cause problems with fertility later in life, a study carried out in rats suggests.

It’s as if low levels of oxygen caused the female’s ovarian tissue to age faster

Catherine Aiken

dife88

Hand Smoking Woman

Researcher profile: Dr Catherine Aiken

“ ̽��ֱ��very first time I delivered a baby, I was both terrified and thrilled – overwhelmed by the enormity of suddenly having a whole new human being in my hands,” says Dr Catherine Aiken. “That moment I knew I absolutely wanted to focus my research on understanding the problems that occur really early in development, and make sure that all children are born with the best start possible in life.”

Catherine grew up in Northern Ireland, but like many Cambridge researchers came to the ̽��ֱ�� as an undergraduate to study medicine, and “never really left”. For the last ten years, she has combined training in maternal and fetal medicine with parallel research projects.

“Currently I spend half of my time looking after mothers with high-risk pregnancies and delivering their babies, and the other half of my time leading studies looking into how pregnancy affects long-term health.”

Catherine’s clinical work takes place at the Rosie Hospital, part of Addenbrooke’s and Cambridge ̽��ֱ�� Hospital NHS Foundation Trust, where she holds clinics, carries out operations, and is on call for obstetric emergencies.

She loves the way the two sides of her work – the clinical and the academic – complement each other. “ ̽��ֱ��adrenaline of an obstetric emergency, where you have not one but two lives in your hands, and the incredible satisfaction of handing a mother a healthy baby after a complicated delivery, is something I could never give up. But I also know that in my clinical practice I am only helping one person at a time, whereas research findings can potentially affect the lives of millions.”

Catherine’s research sets out to explain how and why conditions in the womb have such a major impact on our health, even decades later. If we can understand how the very early environment shapes our likelihood of developing particular health problems, then these are the first steps towards putting protection in place to prevent them. Preventing diseases is so much more effective and economic than trying to treat them after the issues have taken hold.

“I want women experiencing pregnancy complications to get treatment that protects their baby’s health in the long-term as well as immediately. We’re getting better and better at improving the immediate outcomes (though there is still some way to go) but we need more focus on long-term and population health.”

Cambridge has a large community of researchers focused on health in early life, making it an ideal place for Catherine’s own work. “We even have an entire research centre devoted to the placenta!” she says, referring to the Centre for Trophoblast Research.

“Cambridge is full of researchers who are pushing the boundaries of what is possible in terms of state-of-the-art imaging and molecular biology techniques. There is almost no technical advance I can think of for my research, where there isn’t someone in Cambridge I can call who knows everything about it!”

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Breath of life: how your risk of heart disease may stem back to your time in the womb

cjb250 — Tue, 11 Jul 2017 08:00:07 +0000

̽��ֱ��history of science is littered with self-experimenters so passionate about their work that they used themselves as human guinea pigs, however ill-advisedly.

Sir Joseph Barcroft (1872–1947) was one such character. Professor of Physiology at Cambridge, he was best known for his studies of the oxygenation of blood. He also led mountain expeditions where he analysed the oxygen content of his blood and that of other expedition members.

In the middle of his career, Barcroft built an airtight glass chamber in his laboratory in Cambridge. There, he could live and exercise at oxygen levels equivalent to 16,000 feet. Like many self-experimentation stories, things did not always go to plan: in one experiment, he had to be rescued by colleagues after spending six days in the chamber and reportedly turning blue.

Despite his occasional misguided venture, Barcroft’s scientific legacy was significant and so, in his honour, the ̽��ֱ�� of Cambridge has recently opened a new state-of-the-art facility in his name. Research at the Barcroft Centre focuses on farm animals – mainly sheep and chickens, but also pigs – to model important aspects of human physiology.

̽��ֱ��Centre’s work spans several areas including Professor Jenny Morton’s studies on understanding fatal neurodegenerative diseases such as Huntington’s disease and a similar childhood disease, Batten disease, and Dr Frances Henson’s work on bone diseases such as osteoarthritis.

However, a significant amount of its work focuses on how we develop in the womb and how this programmes us for increased risk of heart disease in later life. This seems fitting as, in later years, Barcroft became interested in fetal development, and in particular the effects of low levels of oxygen on the unborn baby in the womb.

Carrying on this legacy are Professor Dino Giussani and his postdocs Dr Kim Botting and Dr Youguo Niu. All are also members of the Centre for Trophoblast Research (CTR), which this year celebrates its tenth anniversary and focuses on the interactions between the pregnant mother and the fetus, as mediated by the placenta.

Low levels of oxygen – or hypoxia – can occur in high-altitude pregnancies. But, as Giussani explains, there are far more common causes. “Smoking, pre-eclampsia, even maternal obesity – these all increase the risk of hypoxia for the mother’s baby, as do inherited genetic variants,” he says.

Housed in the Barcroft Centre is a suite of hypoxia chambers – superficially similar, perhaps, to that in which Barcroft placed himself, but nowadays far more sophisticated (and much safer). These are not intended for humans, but rather for animals, each of which is very closely monitored, often remotely using technology developed by the team.

̽��ֱ��smallest of these chambers doubles as an incubator for fertilised hens’ eggs. Scientists can watch the development of the fetus directly. They can see how the heart grows, for example, how it is affected by hypoxia, and what effect potential drugs have in ameliorating possible complications.

Of course, we grow in a womb, with a placenta connecting us to our mother and controlling our nutritional intake. Mice and rats are the most commonly used mammals in research, but to model mammalian development in longer-living species with similar rates of development to humans, it is necessary to turn to larger animals. Sheep make a good model. Not only is their gestation – and postnatal life – more comparable to a human’s than to a rat’s, but a newborn lamb’s physiology is also similar in a crucial way to a newborn baby’s: its heart is mature at birth. By comparison, a newborn rat’s heart is still very immature.

For part of gestation, the sheep are placed in hypoxia chambers, which contain finely controlled, lower-than-normal levels of oxygen. “This reduces the amount of oxygen in the blood of the pregnant sheep and thereby in her fetus,” explains Botting. “This mimics conditions where the placenta is not working appropriately, as in pregnancy complicated by pre-eclampsia or maternal obesity.”

̽��ֱ��pregnant ewes deliver outside the chambers in normal ambient air. Once born, most of the lambs are put out to pasture in the paddocks adjacent to the Centre, where they grow to adulthood.

“ ̽��ֱ��lambs which were hypoxic in the womb are not noticeably different,” says Giussani. “ ̽��ֱ��sheep will effectively live a normal life. That is the very point, because underneath, a silent killer is brewing; we want to investigate what happens as they grow because there is a theory that a complicated pregnancy may increase the risk of heart disease in the offspring later in life.”

Professor Abby Fowden, Head of the School of the Biological Sciences, and another CTR member and user of the Barcroft Centre, says that the facilities are unique. “It’s probably the only centre in the UK that has the capacity – the surgical and care facilities – to do these kinds of long-term developmental and neurodegenerative studies,” she explains.

Like Giussani, Fowden and her collaborator Dr Alison Forhead are interested in how the early environment in the womb programmes us for disease in later life. They are particularly interested in the role of hormones – in both the mother and the fetus – and how they affect growth and development.

There are some conditions, such as hypothyroidism – whereby the body produces insufficient thyroid hormones – and maternal stress, that probably affect normal fetal development, but about which surprisingly little is understood. To model these conditions, Fowden and Forhead again turn to a range of mammals including sheep and pigs.

As Forhead explains, normal development of the fetus is crucial for health in later life. “In the case of many organs, you’re born with a certain number of functional units, and in postnatal life you don’t have the capacity to change that number. So the number you’re born with has long-lasting consequences.”

Take nephrons, for example. These are functional units of our kidneys that filter the blood and are responsible for how much salt and water is excreted into the urine. “If you’re born with fewer nephrons, this has consequences for how much salt you retain, setting you up in later life to be at greater risk of developing high blood pressure.”

What is apparent from this work is just how much of disease in later life is programmed in the womb. While our lifestyle – our diet, how much we exercise after birth – plays an important role in whether we develop heart disease or type 2 diabetes, for example, much of the risk is present before we are even born, programmed during pregnancy into how our DNA and tissues function.

And these effects don’t necessarily stop at the next generation, as Giussani is discovering in his parallel work with rodents, which allows two or more generations to be studied in a comparably short time.

“If we look at the ‘grandchildren’ of pregnant rats that had a hypoxic pregnancy, we see this disease risk being passed on again, but in a really interesting way,” he says. “A male ‘child’ passes on the cardiovascular risk to the ‘grandchild’, but female offspring confer protection. This is really exciting as inheritable protection against a future risk of heart disease has never been demonstrated in mammals.”

In other words, while we must still recognise our own contribution to our risk of developing certain diseases, some of this risk was programmed into us before we were born: in fact, even before our parents were born. Work at the Barcroft Centre – in monitoring animals for not just one generation but several – will be vital for understanding the consequences of pregnancy not only for our children but also for their children – and even their children’s children.

Inset image: Joseph Barcroft.

Smoking, lack of exercise, bad diet and our genes are all well-known risk factors for heart disease, cancer and diabetes. But, as researchers are beginning to understand, the environment in the womb as we first begin to grow may also determine our future.

Underneath, a silent killer is brewing... there is a theory that a complicated pregnancy may increase the risk of heart disease in the offspring later in life.

Dino Giussani

Ryan Melaugh

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Blood pressure breakthrough holds real hope

bjb42 — Thu, 07 Oct 2010 00:00:00 +0000

After 20 years of research, scientists from the ̽��ֱ�� of Cambridge have now cracked the first step in the main process that controls blood pressure. Their findings, published today in the journal Nature, are likely to have significant implications for the treatment of pre-eclampsia as well as high blood pressure (also known as hypertension).

Blood pressure is controlled by hormones called angiotensins, which cause the blood vessels to constrict. These hormones are released by the protein angiotensinogen. Until now, it was not understood how this occurred.

Dr Aiwu Zhou, a British Heart Foundation (BHF) Fellow at the ̽��ֱ�� of Cambridge, who made the breakthrough, said: "Although we primarily focused on pre-eclampsia, the research also opens new leads for future research into the causes of hypertension in general."

To make the discovery, the researchers solved the structure of angiotensinogen with the help of an extremely intense X-ray beam produced by Diamond Light Source, the UK synchrotron. Their results revealed that the protein is oxidised and changes shape

to permit ready access to angiotensinogen by an enzyme, renin. Renin cuts off the tail of the protein to release the hormone angiotensin, which then raises blood pressure.

Taking their lab results into the clinic at the ̽��ֱ�� of Nottingham, the research team showed that the amount of oxidised, and hence more active, angiotensinogen was increased in women with pre-eclampsia.

Professor Robin Carrell at the ̽��ֱ�� of Cambridge, who led the 20-year research project, explained: "During pregnancy oxidative changes can occur in the placenta. These changes, the very ones we have found stimulates the release of the hormone angiotensin and lead to increased blood pressure, can arise as the circulation in the placenta readjusts the oxygen requirements of the growing foetus with the delivery of oxygen to the placenta from the mother."

Drugs currently used to treat high blood pressure - such as ACE inhibitors - focus on the later stages of the mechanism that controls blood pressure. Today's findings, which give insight into the previously mysterious early stages of the regulation process, provide scientists with new opportunities to research novel treatments for hypertension.

Professor Peter Weissberg, Medical Director of the BHF, which largely funded the study, said: "Every year in the UK pre-eclampsia is responsible for the deaths of around six women and several hundred babies. This research is of the highest quality and offers real hope for developing strategies to prevent or treat this dangerous condition by targeting the process that these scientists have identified. And of course, although the researchers only looked at pre-eclampsia in this study, similar strategies may be useful for those people with high blood pressure that is not effectively controlled by current medicines."

High blood pressure frequently affects pregnancy. However, in 2-7 per cent of pregnancies this develops into pre-eclampsia, which threatens the health and survival of both the mother and child. In Britain, it affects about one in 20 women during pregnancy, and every year 50,000 women and 500,000 infants die globally as a result of pre-eclampsia. There is no treatment for pre-eclampsia and often the mother is either induced early or undergoes a Caesarean.

̽��ֱ��research was largely funded by the British Heart Foundation, with additional funding provided by the Medical Research Council, the Wellcome Trust and the Isaac Newton Trust.

Photo credit: House of Sims

Scientists have discovered a mechanism which raises blood pressure in pre-eclampsia, a potentially deadly condition which occurs during pregnancy.

This research is of the highest quality and offers real hope for developing strategies to prevent or treat this dangerous condition by targeting the process that these scientists have identified."

Professor Peter Weissberg, Medical Director of the BHF

Lemuel Cantos from Flickr

blood pressure

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Prenatal origins of heart disease

bjb42 — Sun, 04 Jan 2009 15:27:10 +0000

Heart disease is the greatest killer in the UK today, accounting for four in every 10 deaths and imposing a substantial burden on the nation’s health and wealth. ̽��ֱ��concept is familiar to us all that traditional risk factors, such as smoking and obesity, and genetic makeup increase the risk of heart disease. However, it is now becoming apparent that a third factor is at play – a developmental programming that is predetermined before birth, not only by our genes but also by their interaction with the quality of our prenatal environment.

A biological trade-off

Pregnancies that are complicated by adverse conditions in the womb, such as happens during pre-eclampsia or placental insufficiency, enforce physiological adaptations in the unborn child and placenta. While these adaptations are necessary to maintain viable pregnancy and sustain life before birth, the adaptations come at a cost, claiming reduced growth as a biological trade-off. In fact it’s more than just growth that is affected – we now know that the trade-off extends to the development of key organs and systems such as the heart and circulation, which increases the risk of cardiovascular disease in adult life. Overwhelming evidence in more than a dozen countries has linked development under sub-optimal intrauterine conditions leading to low birth weight with increased rates in adulthood of coronary heart disease and its major risk factors – hypertension, atherosclerosis and diabetes.

̽��ֱ��idea that a fetus’ susceptibility to disease in later life could be programmed by the conditions in the womb has been taken up vigorously by the international research community, with considerable efforts focusing on nutrient supply across the placenta as a risk factor. But nutrient supply is just part of the story. How much oxygen is available to the fetus is also a determinant of growth and the risk of adult disease. Dr Dino Giussani’s research group in the Department of Physiology, Development and Neuroscience is asking what effect reduced oxygen has on fetal development by studying populations at high altitude.

Lessons from high altitude

Bolivia lies at the heart of South America, split by the Andean Cordillera into areas of very high altitude to the west and areas at sea-level to the east, as the country extends into the Amazon Basin. At 400 m and almost 4000 m above sea-level, respectively, the Bolivian cities of Santa Cruz and La Paz are striking examples of this difference.

Pregnancies at high altitude are subjected to a lower partial pressure of oxygen in the atmosphere compared with those at sea-level. Women living at high altitude in La Paz are more likely to give birth to underweight babies than women living in Santa Cruz. But is this a result of reduced oxygen in the womb or poorer nutritional status?

̽��ֱ��research team studied birth weight records from healthy term pregnancies in La Paz and Santa Cruz, especially from obstetric hospitals and clinics selectively attended by women from either high- or low-income backgrounds. High-altitude babies showed a pronounced reduction in birth weight compared with low-altitude babies, even in cases of high maternal nutritional status. Babies born to low-income mothers at sea-level also showed a reduction in birth weight, but the effect of under-nutrition was not as pronounced as the effect of high altitude on birth weight; clearly, fetal oxygenation was a more important determinant of fetal growth within these communities

Remarkably, although one might assume that babies born to low-income mothers at high altitude would show the greatest reduction in birth weight, these babies were actually heavier than babies born to high-income mothers at high altitude. It turns out that the difference lies in ancestry. ̽��ֱ��lower socio-economic groups of La Paz are almost entirely made up of Aymara Indians, an ancient ethnic group with a history in the Bolivian highlands spanning two millennia. On the other hand, individuals of higher socio-economic status in Bolivia represent a largely European and North American admixture, relative newcomers to high altitude. It seems therefore that an ancestry linked to prolonged high-altitude residence confers protection against reduced atmospheric oxygen.

Do these early influences of oxygenation feed through to increased risk of cardiovascular disease? A large-scale, five-year study to determine this has been initiated in the two cities that will link birth weight data with measurements of cardiovascular health and disease in Bolivian high- and lowlanders. But an early indication has been supplied by a somewhat unlikely source: Bolivian hen eggs.

Mountain chicks

Dr Giussani’s group has discovered that they can replicate the results found in Andean pregnancies in eggs: fertilised eggs from Bolivian hens native to sea-level show growth restriction when incubated at high altitude, whereas eggs from hens that are native to high altitude show a smaller growth restriction. Using hen eggs has allowed the researchers to accomplish something that would take generations of migration in human populations to demonstrate: moving fertilised eggs from hens native to high altitude down to sea-level. This not only restored growth, but the embryos were actually larger than sea-level embryos incubated at sea-level. And, importantly, when looking for early markers of cardiovascular disease, it was discovered that growth restriction at high altitude was indeed linked with cardiovascular defects – shown by an increase in the thickness of the walls of the chick heart and aorta.

Bringing the Andes to Cambridge

To have hopes of clinical intervention, we need to understand why reduced oxygen should be a trigger for a prenatal origin of heart disease. Towards this goal, the group’s most recent data studying rat pregnancy complicated with reduced fetal oxygenation have indicated that the adverse effects on cardiovascular development may be secondary to a disturbance known as oxidative stress. ̽��ֱ��body normally produces by-products of oxygen called free radicals and, unless these are neutralised by antioxidants, they cause damage to cells. If oxidative stress is the underlying cause of cardiovascular defects, this offers the highly interesting possibility of using antioxidants to treat pregnancies complicated by reduced oxygen delivery to the fetus, be it at sea-level or high altitude. This may halt the development of heart disease at its very origin, bringing preventive medicine back into the womb.

For more information, please contact the author Dr Dino Giussani (dag26@cam.ac.uk) at the Department of Physiology, Development and Neuroscience. Research described here was sponsored by the British Heart Foundation, Biotechnology and Biological Sciences Research Council (BBSRC), Lister Institute of Preventive Medicine, Royal Society and Wellcome Trust. Dr Giussani is a member of the Centre for Trophoblast Research.

Studies in La Paz, the highest city in the world, are helping to uncover a link between prenatal conditions and heart disease in later life.

High-altitude babies showed a pronounced reduction in birth weight compared with low-altitude babies, even in cases of high maternal nutritional status.

Kristin Gussani

La Paz, Chile

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Great expectations in pregnancy research

amb206 — Fri, 01 Feb 2008 00:00:00 +0000

Complications in pregnancy represent a persistent and major problem in public health. ̽��ֱ��first three months after conception are known to be the most critical, with as many as 20% of pregnancies lost during this time. For pregnancies that develop beyond 24 weeks, between 0.5 and 1% result in death of the baby, either in the womb or in the first four weeks of life. Premature birth can incur major complications associated with delivery, immediate care of the infant, childhood diseases, and educational and social problems in later life. Not only is there an emotional cost to families, but an economic assessment in the USA reported that the cumulative subsequent healthcare and social costs associated with one year’s worth of pre-term deliveries was $26 billion. Understanding and intervening to prevent these events is clearly crucial.

Although some advances have been made, the dismaying fact is that the rates of stillbirth have generally remained static over the past 20–30 years. This partly reflects an incomplete understanding of the biological events that lead to these complications of pregnancy. Determining what these mechanisms might be is essential for devising new strategies of intervention, and applying in-depth scientific studies to human pregnancy is now seen as vital.

Two multidisciplinary initiatives in Cambridge have recently embarked on improving our understanding of pregnancy and its outcomes: a large antenatal screening of women at the Rosie Maternity Hospital in Cambridge and the recent endowment of a Centre for Trophoblast Research within the School of Biological Sciences. Both initiatives build on the wealth of expertise in the biology of pregnancy that exists across Cambridge.

Screening for adverse outcomes

A four-year research project that aims to monitor 5000 pregnant women commenced in 2007 under the leadership of Professor Gordon Smith in the ̽��ֱ��’s Department of Obstetrics and Gynaecology. A multidisciplinary team of translational researchers in both the School of Clinical Medicine and the School of Biological Sciences are participating in the project, which is funded under the Women’s Health theme of the UK Department of Health’s Cambridge Comprehensive Biomedical Research Centre.

Women enrolling in the study are scanned and give blood samples at 12, 20, 28 and 36 weeks of gestation, allowing detailed characterisation of the baby’s growth and development. Thanks to an industrial collaboration with GE Healthcare, the long-term loan of two state-of-the-art scanners will enable real-time three-dimensional scanning of the babies in utero. At birth, samples of placenta and cord blood will be obtained and stored.

̽��ֱ��study is prospective; for those women whose pregnancies sadly have complications or adverse outcomes (such as pre-eclampsia, spontaneous pre-term birth, stillbirth or low-birth-weight babies), the stored samples will be retrieved and compared with controls. These samples then become the focus of extensive clinical and biological analyses to try to establish the cause. Studies will analyse the development and function of the placenta and the effect of oxidative stress; the expression or silencing of genes in relation to whether they came from the mother or the father (known as genomic imprinting); the maternal–foetal immune interaction; and the genes that are expressed in the placenta. ̽��ֱ��MRC Epidemiology Unit will conduct follow-up studies of the growth and development of the babies who have been carefully monitored during the pregnancy.

̽��ֱ��hope is that this detailed characterisation of foetal development, on such a large scale, will lead to mechanistic studies on the causes of common clinical problems in pregnancy. As well as providing refined risk assessment, novel treatments might be identified that could improve the outcome of pregnancies in women deemed to be at higher risk.

Centre for Trophoblast Research

̽��ֱ��recent endowment of the Centre for Trophoblast Research, due to be launched on 9 July 2008, is a highly innovative initiative aimed at promoting research into trophoblast biology both within Cambridge and on the wider national and international stages. ̽��ֱ��trophoblast is the cell type that forms the interface between the foetus and its mother, supplying nutrients to support the growth of the foetus. It is fundamental to successful pregnancy and must interact intimately with the maternal cells lining the uterus, leading to the formation of the placenta.

In humans, this interaction is particularly invasive and, during the first few weeks of pregnancy, the foetus becomes completely embedded within the wall of the uterus. This form of placentation, seen only among the great apes, poses unique immunological and haemodynamic challenges. ̽��ֱ��invading trophoblast cells, which are genetically related to, but distinct from, those of the mother, must negotiate passage with her immune system to allow them to reach their target – the specialised blood vessels in the wall of the uterus. As a result of this invasion, the vessels undergo major structural changes that ensure the placenta has a plentiful and continuous supply of blood in later pregnancy.

There is now abundant evidence that the major complications of pregnancy are associated with deficient trophoblast invasion, resulting in aberrant maternal blood flow to the placenta. Research performed in Cambridge has demonstrated that, paradoxically, too much flow in early pregnancy results in miscarriage, whereas too little in later pregnancy is associated with low birth weight and pre-eclampsia. These new insights have radically changed our understanding of human pregnancy and have helped to explain why miscarriage and pre-eclampsia are virtually unique to humans. Studying trophoblast biology is therefore not only of basic scientific interest but is also key to understanding the root causes of these pregnancy disorders.

Raising hopes for future pregnancies

̽��ֱ��aim of these multidisciplinary initiatives across Cambridge is to arrive at a better understanding of the biology of normal and complicated human pregnancy. Only by doing so can scientists hope to develop new diagnostic tests to identify women at increased risk of complications and, potentially, new interventions that might prevent the life-long effects of these complications on mothers and their children.

Participating researchers

Antenatal screening initiative (Principal Investigator: Prof Gordon Smith)

Dr Steve Charnock-Jones and Dr Miguel Constância (Dept of Obstetrics and Gynaecology); Prof Graham Burton, Prof Abby Fowden, Dr Dino Giussani and Dr Anne Ferguson-Smith (Dept of Physiology, Development and Neuroscience); Dr Ashley Moffett (Dept of Pathology); Prof David Dunger (Dept of Paediatrics); Dr Ian White (MRC Biostatistics Unit); Dr Ken Ong (MRC Epidemiology Unit).

̽��ֱ��project is within the Women’s Health theme of the Cambridge Comprehensive Biomedical Research Centre – a partnership between Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust and the ̽��ֱ�� of Cambridge, and created by the National Institute for Health Research (NIHR). These themes focus on translating advances in basic medical research from the laboratory to the hospital clinic.

Centre for Trophoblast Research (Director: Prof Graham Burton)

Participating researchers will be announced in 2008. ̽��ֱ��Centre will facilitate research by providing flexible and responsive funding for seminars, workshops and visiting scholars, as well as laboratory space in the Department of Physiology, Development and Neuroscience. ̽��ֱ��Centre also aims to encourage the next generation through graduate studentships and postdoctoral fellowships.

For more information, please contact the authors Professor Gordon Smith at the Department of Obstetrics and Gynaecology (gcss2@cam.ac.uk) or Professor Graham Burton at the Department of Physiology, Development and Neuroscience (gjb2@cam.ac.uk). Please go towww.trophoblast.cam.ac.ukfor more information about the Centre for Trophoblast Research.

Most pregnancies develop normally but when complications arise they can have devastating effects. Two recent initiatives in Cambridge hope to deliver a new understanding of events during this critical period of human life.

Thanks to an industrial collaboration with GE Healthcare, the long-term loan of two state-of-the-art scanners will enable real-time three-dimensional scanning of the babies in utero.

Professor Graham Burton

Human placental villi showing signs of oxidative stress

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