̽��ֱ�� of Cambridge - Cambridge Reproduction

̽��ֱ��Cambridge Awards 2024 for Research Impact and Engagement

zs332 — Mon, 03 Feb 2025 10:27:01 +0000

Meet the winner of the Cambridge Awards 2024 for Research Impact and Engagement and learn more about their projects.

Cambridge scientists elected as Members of the European Molecular Biology Organisation

jg533 — Tue, 09 Jul 2024 12:00:56 +0000

Five Cambridge researchers join the community of over 2,100 leading life scientists today as the European Molecular Biology Organisation (EMBO) announces its newest Members in its 60th anniversary year.

Pioneering Code of Practice released for use of stem cell-based embryo models in research

jg533 — Thu, 04 Jul 2024 08:17:57 +0000

̽��ֱ�� ̽��ֱ�� of Cambridge, in partnership with the Progress Educational Trust, has led work to create the first ever UK guidelines for the generation and use of stem cell-based embryo models in research.

‘Mini-placentas’ help scientists understand the causes of pre-eclampsia and pregnancy disorders

cjb250 — Wed, 17 Jan 2024 16:00:37 +0000

̽��ֱ��study, published today in Cell Stem Cell, shows that it is possible to experiment on a developing human placenta, rather than merely observe specimens, in order to study major disorders of pregnancy.

Successful pregnancy depends on the development of the placenta in the first few weeks of gestation. During this period, the placenta implants itself into the endometrium – the mucosal lining of the mother’s uterus.

Interactions between the cells of the endometrium and the cells of the placenta are critical to whether a pregnancy is successful. In particular, these interactions are essential to increase the maternal blood supply to the placenta, necessary for fetal growth and development.

When these interactions do not work properly, they can lead to complications, such as pre-eclampsia, a condition that causes high blood pressure during pregnancy. Pre-eclampsia occurs in around six in 100 first pregnancies and can put at risk the health of both the mother and the baby.

Professor Ashley Moffett from the Department of Pathology at the ̽��ֱ�� of Cambridge said: “Most of the major disorders of pregnancy – pre-eclampsia, still birth, growth restriction, for example – depend on failings in the way the placenta develops in the first few weeks. This is a process that is incredibly difficult to study – the period after implantation, when the placenta embeds itself into the endometrium, is often described as a ‘black box of human development’.

“Over the past few years, many scientists – including several at Cambridge – have developed embryo-like models to help us understand early pre-implantation development. But further development is impeded because we understand so little about the interactions between the placenta and the uterus.”

Professor Moffett and colleagues at the Friedrich Miescher Institute, Switzerland, and the Wellcome Sanger Institute, Cambridge, have used ‘mini-placentas’ – a cellular model of the early stages of the placenta – to provide a window into early pregnancy and help improve our understanding of reproductive disorders. Known as ‘trophoblast organoids’, these are grown from placenta cells and model the early placenta so closely that they have previously been shown to record a positive response on an over-the-counter pregnancy test.

In previous work, Professor Moffett and colleagues identified genes that increase the risk of or protect against conditions such as pre-eclampsia. These highlighted the important role of immune cells uniquely found in the uterus, known as ‘uterine natural killer cells’, which cluster in the lining of the womb at the site where the placenta implants. These cells mediate the interactions between the endometrium and the cells of the placenta.

In their new study, her team applied proteins secreted by the uterine natural killer cells to the trophoblast organoids so that they could mimic the conditions where the placenta implants itself. They identified particular proteins that were crucial to helping the organoids develop. These proteins will contribute to successful implantation, allowing the placenta to invade the uterus and transform the mother’s arteries.

“This is the only time that we know of where a normal cell invades and transforms an artery, and these cells are coming from another individual, the baby,” said Professor Moffett, who is also a Fellow at King’s College, Cambridge.

“If the cells aren’t able to invade properly, the arteries in the womb don’t open up and so the placenta – and therefore the baby – are starved of nutrients and oxygen. That's why you get problems later on in pregnancy, when there just isn't enough blood to feed the baby and it either dies or is very tiny.”

̽��ֱ��researchers also found several genes that regulate blood flow and help with this implantation, which Professor Moffett says provide pointers for future research to better understand pre-eclampsia and similar disorders.

Dr Margherita Turco, from the Friedrich Miescher Institute in Switzerland and co-lead of this work, added: “Despite affecting millions of women a year worldwide, we still understand very little about pre-eclampsia. Women usually present with pre-eclampsia at the end of pregnancy, but really to understand it – to predict it and prevent it – we have to look at what's happening in the first few weeks.

“Using ‘mini-placentas’, we can do just that, providing clues as to how and why pre-eclampsia occurs. This has helped us unpick some of the key processes that we should now focus on far more. It shows the power of basic science in helping us understand our fundamental biology, something that we hope will one day make a major difference to the health of mothers and their babies.”

̽��ֱ��research was supported by Wellcome, the Royal Society, European Research Council and Medical Research Council.

Reference
Li, Q et al. Human uterine natural killer cells regulate differentiation of extravillous trophoblast early in pregnancy. Cell Stem Cell; 17 Jan 2024; DOI: doi.org/10.1016/j.stem.2023.12.013

Volunteers wanted for women's health study

̽��ֱ�� of Cambridge researchers at Addenbrooke’s Hospital are looking for volunteers who are planning their first pregnancy, to take part in a new study focussing on pregnancy and women’s long-term health (the POPPY study).

̽��ֱ��POPPY study aims to understand why some women develop pre-eclampsia and other placental complications and why these conditions have an adverse effect on women’s future heart health.

If you are aged 18-45 years and are planning your first pregnancy, you may be eligible to participate. We are also looking for similar aged volunteers who are not actively planning a pregnancy, for a control group.

Reimbursement is provided for time, inconvenience and travel.

To find out more, please visit the POPPY study website or email the POPPY study team.

18 January 2024

Scientists have grown ‘mini-placentas’ in the lab and used them to shed light on how the placenta develops and interacts with the inner lining of the womb – findings that could help scientists better understand and, in future, potentially treat pre-eclampsia.

Most of the major disorders of pregnancy – pre-eclampsia, still birth, growth restriction, for example – depend on failings in the way the placenta develops in the first few weeks. This is a process that is incredibly difficult to study.

Ashley Moffett

Friedrich Miescher Institute/ ̽��ֱ�� of Cambridge

Placental organoid (circle in the centre). Trophoblast cells are invading out of the organoid, mimicking placental cells invading the uterus in the early weeks of pregnancy.

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Thousands of pregnancies tracked in UK’s biggest study on pre-eclampsia

Anonymous — Wed, 19 Jul 2023 10:16:45 +0000

̽��ֱ��POPPY study (Preconception to pOst-partum study of cardiometabolic health in Primigravid PregnancY) is funded by Wellcome and is being led by a team from Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust (CUH) and the ̽��ֱ�� of Cambridge. ̽��ֱ��study is also being carried out in Glasgow and up to four other research centres in London.

In the first large scale study of its kind in the UK, women are being monitored before, during and after their first pregnancy to see what factors might be influencing the health of their placenta and their long-term cardiovascular risk. It’s hoped that by understanding this risk, the health of women who develop placental complications can also be improved over their lifetime.

Placental complications affect around 1 in 10 pregnancies and includes:

pre-eclampsia (high blood pressure with kidney/liver/brain involvement)
gestational hypertension (high blood pressure in pregnancy)
fetal growth restriction (baby being small).

These conditions can lead to serious complications for both mother and baby if not monitored or treated.

High blood pressure (hypertension), diabetes, autoimmune conditions, age and being obese before pregnancy are just some of the factors likely to increase the risk of pre-eclampsia and placental dysfunction, but it’s unclear exactly why and whether there are other causes.

In addition, women who experience placental complications are twice as likely to develop heart disease and diabetes later in life, compared with women who have a healthy pregnancy.

It’s not clear however whether placental complications cause heart disease and diabetes directly, or whether these conditions happen in women who already have some underlying and/or unknown health issues before pregnancy.

Women thought to be at high risk of developing pre-eclampsia are advised to take a 75 to 150mg daily dose of aspirin from the twelfth week of pregnancy until birth to reduce the risk of developing this condition. If a woman develops pre-eclampsia, the only way to cure it is to deliver the baby, normally at around 37 to 38 weeks of pregnancy, although this can be earlier in more severe cases.

Dr Bernadette Jenner is a medical registrar in obstetric medicine and clinical pharmacology at Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust (CUH) and is leading the POPPY study in Cambridge. She said:

“This study is going to be monitoring thousands of women from before they become pregnant for the first time and will track them through to birth and beyond to try and discover why some develop placental conditions and others don’t. We also hope to find out whether or not these conditions trigger longer-term health issues such as heart disease and diabetes.”

“We have a significant lack of understanding when it comes to placental conditions, especially when you consider how common they are, and the serious impact they can have on women and babies, which at times is life-threatening. To prevent pre-eclampsia and other placental conditions we need to know what really causes them and why. We have some big gaps in our knowledge and this study hopes to find answers.”

Professor Ian Wilkinson is leading the POPPY study and is a clinical pharmacologist and Professor of Therapeutics at the ̽��ֱ�� of Cambridge. He said:

“ ̽��ֱ��POPPY study is a world first and will help us to better understand why common complications of pregnancy adversely affect women’s long term cardiovascular health. This is the key to reducing this risk and may also allow us to prevent pregnancy complications before they occur.”

"Unfortunately, many women who suffer from pre-eclampsia, or one of the other placental complications, are not aware of the potential long term risks, and very few of them are actively followed up after birth - despite recommendations by NICE.”

“Therefore, whilst we await the findings of the POPPY study it is important that women who have experienced one of these complications are seen by a medical professional in the months after delivery to ensure that their blood pressure and other cardiovascular risk factors are checked and treated if necessary."

̽��ֱ��POPPY study is now open at Addenbrooke’s Hospital in Cambridge. Two more sites will be open soon at Glasgow Royal Infirmary NHS and Imperial College Healthcare NHS Trust, with further sites in London to start in the coming months.

Participants must be planning their first pregnancy and live in Glasgow, Cambridge or London where the study is taking place. Participation will involve monitoring alongside regular pregnancy checks and tests.

Find out how you can take part on the POPPY Study website.

Adapted from a press release by CUH

Up to 3,500 first time mums are due to take part in a study led by Cambridge researchers to understand why some will develop pre-eclampsia and placental complications during pregnancy and whether it effects their long-term health.

We have a significant lack of understanding when it comes to placental conditions, especially when you consider how common they are, and the serious impact they can have on women and babies, which at times is life-threatening

Bernadette Jenner

POPPY study | Dr Bernadette Jenner

Suhyeon Choi

Pregnant person holding her stomach

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Cell mapping and ‘mini placentas’ give new insights into human pregnancy

jg533 — Wed, 29 Mar 2023 16:12:59 +0000

Researchers from the ̽��ֱ�� of Cambridge, the Wellcome Sanger Institute, the Friedrich Miescher Institute for Biomedical Research (FMI), Switzerland, EMBL’s European Bioinformatics Institute (EMBL-EBI), and collaborators, have created an in-depth picture of how the placenta develops and communicates with the uterus.

̽��ֱ��study, published today in the journal Nature, is part of the Human Cell Atlas initiative to map every cell type in the human body. It informs and enables the development of experimental models of the human placenta.

"For the first time, we have been able to draw the full picture of how the placenta develops and describe in detail the cells involved in each of the crucial steps. This new level of insight can help us improve laboratory models to continue investigating pregnancy disorders, which cause illness and death worldwide,” said Anna Arutyunyan, co-first author at the ̽��ֱ�� of Cambridge and Wellcome Sanger Institute.

̽��ֱ��placenta is a temporary organ built by the foetus that facilitates vital functions such as foetal nutrition, oxygen and gas exchange, and protects against infections. ̽��ֱ��formation and embedding of the placenta into the uterus, known as placentation, is crucial for a successful pregnancy.

Understanding normal and disordered placentation at a molecular level can help answer questions about poorly understood disorders including miscarriage, stillbirth, and pre-eclampsia. In the UK, mild pre-eclampsia affects up to six per cent of pregnancies. Severe cases are rarer, developing in about one to two per cent of pregnancies.

Many of the processes in pregnancy are not fully understood, despite pregnancy disorders causing illness and death worldwide. This is partly due to the process of placentation being difficult to study in humans, and while animal studies are useful, they have limitations due to physiological differences.

During its development, the placenta forms tree-like structures that attach to the uterus, and the outer layer of cells, called trophoblast, migrate through the uterine wall, transforming the maternal blood vessels to establish a supply line for oxygen and nutrients.

In the new study, scientists built on previous work investigating the early stages of pregnancy, to capture the process of placental development in unprecedented detail. Cutting-edge genomic techniques allowed them to see all of the cell types involved and how trophoblast cells communicate with the maternal uterine environment around them.

̽��ֱ��team uncovered the full trajectory of trophoblast development, suggesting what could go wrong in disease and describing the involvement of multiple populations of cells, such as maternal immune and vascular cells.

"This research is unique as it was possible to use rare historical samples that encompassed all the stages of placentation occurring deep inside the uterus. We are glad to have created this open-access cell atlas to ensure that the scientific community can use our research to inform future studies,” said Professor Ashley Moffett, co-senior author at the ̽��ֱ�� of Cambridge's Department of Pathology.

They also compared these results to placental trophoblast organoids, sometimes called ‘mini-placentas’, that are grown in the lab. They found that most of the cells identified in the tissue samples can be seen in these organoid models. Some later populations of trophoblast are not seen and are likely to form in the uterus only after receiving signals from maternal cells.

̽��ֱ��team focussed on the role of one understudied population of maternal immune cells known as macrophages. They also discovered that other maternal uterine cells release communication signals that regulate placental growth.

̽��ֱ��insights from this research can start to piece together the unknowns about this stage of pregnancy. ̽��ֱ��new understanding will help in the development of effective lab models to study placental development and facilitate new ways to diagnose, prevent, and treat pregnancy disorders.

This research was funded by Wellcome, ̽��ֱ��Royal Society, and the European Research Council.

Reference

Arutyunyan, A et al: 'Spatial multiomics map of trophoblast development in early pregnancy.' March 2023, Nature. DOI: 10.1038/s41586-023-05869-0

Adapted from a press release by the Wellcome Sanger Institute.

Researchers have mapped the complete trajectory of placental development, helping shed new light on why pregnancy disorders happen.

This can help us improve laboratory models to continue investigating pregnancy disorders, which cause illness and death worldwide.

Anna Arutyunyan

Kenny Roberts, Wellcome Sanger Institute

Cells of the placenta

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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‘Synthetic’ embryo with brain and beating heart grown from stem cells

jg533 — Thu, 25 Aug 2022 15:03:28 +0000

New model embryo, using mouse stem cells, reaches a further point in development than has been achieved in any other stem cell-derived model.

Maternal microbiome promotes healthy development of the baby

jg533 — Tue, 28 Jun 2022 08:23:10 +0000

A new study has found that a species of gut bacteria, known to have beneficial effects for health in mice and humans, changes the mother’s body during pregnancy and affects the structure of the placenta and nutrient transport - which impacts the growing baby.

̽��ֱ��bacteria, Bifidobacterium breve, is widely used as a probiotic so this study could point to ways of combating pregnancy complications and ensuring a healthy start in life across the population.

̽��ֱ��research involved scientists from the ̽��ֱ�� of Cambridge, the Quadram Institute, and the ̽��ֱ�� of East Anglia and is published today in the journal Cellular and Molecular Life Sciences.

Microbes in our gut, collectively called the gut microbiome, are known to play a key role in maintaining health by combating infections, and influencing our immune system and metabolism. They achieve these beneficial effects by breaking down food in our diet and releasing active metabolites that influence cells and body processes.

Little is known about how these interactions influence fetal development and the baby’s health pre-birth. To address this, Professor Lindsay Hall from the Quadram Institute and ̽��ֱ�� of East Anglia, and Dr Amanda Sferruzzi-Perri and Dr Jorge Lopez-Tello from the ̽��ֱ�� of Cambridge analysed how supplementation with Bifidobacterium bacteria affected pregnancy in mice.

Hall has been studying Bifidobacterium and the microbiome in very early life, previously showing how providing specific probiotics can help premature babies. These bacteria rise in numbers in the microbiome during pregnancy in humans and mice, and alterations in its levels have been linked to pregnancy complications.

Sferruzzi-Perri said: “Pregnancy disorders affect around one in ten pregnant women. This is worrying, as pregnancy complications can lead to health problems for the mother and her baby even after the pregnancy.”

“This study, carried out in mice, identifies the maternal microbiome as a new player in the communication between mother, placenta and fetus. Finding out how this form of communication works and how to improve it may help many women who develop pregnancy complications, as well as helping their developing child.”

‘Germ-free’ mice - lacking any microbes – can be bred to allow comparisons with other mice that have a ‘normal’ microbiome. This can provide valuable insights into the role of the microbiome in health - such studies can’t be carried out in humans.

In this study, the researchers also looked at the effect of feeding germ-free mice the probiotic Bifidobacterium breve.

In the germ-free mice, the fetus did not receive adequate sugar and failed to grow and develop properly. Excitingly, providing Bifidobacterium breve to germ-free mice improved fetal outcomes by restoring fetal metabolism, growth and development to the normal levels.

Lacking the maternal microbiome also hampered the growth of the placenta in a way that would affect fetal growth, and more detailed analysis identified a number of key cell growth and metabolic factors that appear to be regulated by the microbiome and Bifidobacterium breve.

“ ̽��ֱ��placenta has been a neglected organ, despite it being vital for the growth and survival of the fetus. A better understanding of how the placenta grows and functions will ultimately result in healthier pregnancies for mothers and babies,” said Lopez-Tello.

̽��ֱ��researchers also found that the microbiome affected key nutrient transporters, including those for sugars within the placenta that would also influence the growth of the fetus.

“Our findings reveal that the maternal microbiome promotes development of the placenta and growth of the fetus,” said Hall.

“We think that this is linked to the altered profile of metabolites and nutrients, which affects nutrient transport from mother to baby across the placenta. Excitingly it appears that adding in a probiotic Bifidobacterium during pregnancy may help to boost how the placenta functions, which has positive effects on the baby’s growth in the womb.”

These findings are strong indicators of a link between the microbiome of the mother and the development of the baby, but in this first study of its kind there are limitations.

This study focused on one single bacterial species, and whilst this showed that Bifidobacterium breve had positive effects on germ-free mice during pregnancy, this is not a natural situation. Future studies are needed to confirm these effects in a more natural and complex microbiome.

̽��ֱ��study was carried out in mice and cannot automatically be translated into treatments for humans. ̽��ֱ��knowledge provided in this proof-of-concept animal study is critical for guiding future studies in humans - to uncover whether the human maternal microbiome has similar effects. If that is the case, it could provide a relatively simple and low-cost way to help improve pregnancy outcomes with positive benefit for the life-long health of the mother and her child.

̽��ֱ��research was funded by Wellcome and the Biotechnology and Biological Sciences Research Council.

Reference

Lopez-Tello, J et al: ‘Maternal gut microbiota Bifidobacterium promotes placental morphogenesis, nutrient transport and fetal growth in mice.’ Cellular and Molecular Life Sciences, June 2022. DOI: 10.1007/s00018-022-04379-y

Adapted from a press release by the Quadram Institute.

Researchers studying mice have found the first evidence of how a mother’s gut microbes can help in the development of the placenta, and the healthy growth of the baby.

This study, carried out in mice, identifies the maternal microbiome as a new player in the communication between mother, placenta and fetus.”

Amanda Sferruzzi-Perri

Hall Lab, Quadram Institute

Bifidobacterium breve

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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