̽��ֱ�� of Cambridge - Amanda Sferruzzi-Perri

Mother’s gut microbiome during pregnancy shapes baby’s brain development

jg533 — Tue, 20 Aug 2024 23:30:03 +0000

Researchers have compared the development of the fetal brain in mice whose mothers had no bacteria in their gut, to those whose mothers were given Bifidobacterium breve orally during pregnancy, but had no other bacteria in their gut.

Nutrient transport to the brain increased in fetuses of mothers given Bifidobacterium breve, and beneficial changes were also seen in other cell processes relating to growth.

Bifidobacterium breve is a ‘good bacteria’ that occurs naturally in our gut, and is available as a supplement in probiotic drinks and tablets.

Obesity or chronic stress can alter the gut microbiome of pregnant women, often resulting in fetal growth abnormalities. ̽��ֱ��babies of up to 10% of first-time mothers have low birth weight or fetal growth restriction. If a baby hasn't grown properly in the womb, there is an increased risk of conditions like cerebral palsy in infants and anxiety, depression, autism, and schizophrenia in later life.

These results suggest that improving fetal development - specifically fetal brain metabolism - by taking Bifidobacterium breve supplements while pregnant may support the development of a healthy baby.

̽��ֱ��results are published today in the journal Molecular Metabolism.

“Our study suggests that by providing ‘good bacteria’ to the mother we could improve the growth and development of her baby while she’s pregnant,” said Dr Jorge Lopez-Tello, a researcher in the ̽��ֱ�� of Cambridge’s Centre for Trophoblast Research, first author of the report.

He added: “This means future treatments for fetal growth restriction could potentially focus on altering the gut microbiome through probiotics, rather than offering pharmaceutical treatments - with the risk of side effects - to pregnant women.”

“ ̽��ֱ��design of therapies for fetal growth restriction are focused on improving blood flow pathways in the mother, but our results suggest we’ve been thinking about this the wrong way - perhaps we should be more focused on improving maternal gut health,” said Professor Amanda Sferruzzi-Perri, a researcher in the ̽��ֱ�� of Cambridge’s Centre for Trophoblast Research and senior author of the report, who is also a Fellow of St John’s College, Cambridge.

She added: “We know that good gut health - determined by the types of microbes in the gut - helps the body to absorb nutrients and protect against infections and diseases.”

̽��ֱ��study was carried out in mice, which allowed the effects of Bifidobacterium breve to be assessed in a way that would not be possible in humans - the researchers could precisely control the genetics, other microorganisms and the environment of the mice. But they say the effects they measured are likely to be similar in humans.

They now plan further work to monitor the brain development of the offspring after birth, and to understand how Bifidobacterium breve interacts with the other gut bacteria present in natural situations.

Previous work by the same team found that treating pregnant mice with Bifidobacterium breve improves the structure and function of the placenta. This also enables a better supply of glucose and other nutrients to the developing fetus and improves fetal growth.

“Although further research is needed to understand how these effects translate to humans, this exciting discovery may pave the way for future clinical studies that explore the critical role of the maternal microbiome in supporting healthy brain development before birth,” said Professor Lindsay Hall at the ̽��ֱ�� of Birmingham, who was also involved in the research.

While it is well known that the health of a pregnant mother is important for a healthy baby, the effect of her gut bacteria on the baby’s development has received little attention.

Reference

Lopez-Tello, J, et al: ‘Maternal gut Bifidobacterium breve modifies fetal brain metabolism in germ-free mice.’ Molecular Metabolism, August 2024. DOI: 10.1016/j.molmet.2024.102004

A study in mice has found that the bacteria Bifidobacterium breve in the mother’s gut during pregnancy supports healthy brain development in the fetus.

AsiaVision on Getty

̽��ֱ��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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Unborn babies use ‘greedy’ gene from dads to ‘remote-control’ mums into feeding them extra food

Anonymous — Tue, 11 Jul 2023 15:00:32 +0000

̽��ֱ��unborn baby ‘remote controls’ its mother’s metabolism so the two are in a nutritional tug of war. ̽��ֱ��mother’s body wants the baby to survive but needs to keep enough glucose and fats circulating in her system for her own health, to be able to deliver the baby, breastfeed and to reproduce again.

A new study from the ̽��ֱ�� of Cambridge published today examines how the placenta communicates with the mother through the release of hormones so she will accommodate her baby’s growth. ̽��ֱ��placenta is a vital organ that develops with the fetus in pregnant women and other female mammals to support the developing fetus. In pregnant mice, scientists selectively altered the signalling cells in the placenta that tell mothers to allocate nutrients to her developing fetuses.

Professor Amanda Sferruzzi-Perri, Professor in Fetal and Placental Physiology, a Fellow of St John’s College and co-senior author of the paper, said: “It’s the first direct evidence that a gene inherited from the father is signalling to the mother to divert nutrients to the fetus.”

Dr Miguel Constancia, MRC Investigator based at the Wellcome-MRC Institute of Metabolic Science and co-senior author of the paper, said: “ ̽��ֱ��baby’s remote control system is operated by genes that can be switched on or off depending on whether they are a ‘dad’s’ or ‘mum’s’ gene’, the so-called imprinted genes.

“Genes controlled by the father are ‘greedy’ and ‘selfish’ and will tend to manipulate maternal resources for the benefit of the fetuses, so to grow them big and fittest. Although pregnancy is largely cooperative, there is a big arena for potential conflict between the mother and the baby, with imprinted genes and the placenta thought to play key roles.”

̽��ֱ��findings by researchers from the Centre for Trophoblast Research at Cambridge’s Department of Physiology, Development and Neuroscience and the Medical Research Council Metabolic Diseases Unit, part of the Wellcome-MRC Institute of Metabolic Science, have been published in Cell Metabolism.

̽��ֱ��baby’s genes controlled by the father tend to promote fetal growth and those controlled by the mother tend to limit fetal growth.

Professor Sferruzzi-Perri explained: “Those genes from the mother that limit fetal growth are thought to be a mother’s way of ensuring her survival, so she doesn’t have a baby that takes all the nutrients and is too big and challenging to birth. ̽��ֱ��mother also has a chance of having subsequent pregnancies potentially with different males in the future to pass on her genes more widely.”

Researchers deleted the expression of an important imprinted gene called Igf2, which provides instructions for making a protein called ‘Insulin Like Growth Factor 2’. Similar to the hormone insulin, which is responsible for making and controlling glucose levels in our circulation, the gene promotes fetal growth and plays a key part in the development of fetal tissues including the placenta, liver and brain.

Dr Jorge Lopez-Tello, a lead author of the study based at the ̽��ֱ��’s Department of Physiology, Development and Neuroscience, said: “If the function of Igf2 from the father is switched off in signalling cells, the mother doesn’t make enough amounts of glucose and lipids – fats – available in her circulation. These nutrients therefore reach the fetus in insufficient amounts and the fetus doesn’t grow properly.”

̽��ֱ��scientists found that deleting Igf2 from the placenta’s signalling cells affects the production of other hormones that modulate the way the mother’s pancreas produces insulin, and how her liver and other metabolic organs respond.

“We found Igf2 controls the hormones responsible for reducing insulin sensitivity in the mother during pregnancy. It means the mother’s tissues don’t absorb glucose so nutrients are more available in the circulation to be transferred to the fetus,” said Professor Sferruzzi-Perri.

Babies with Igf2 gene defects can be overgrown or growth-stunted. “Until now, we didn’t know that part of the Igf2 gene’s role is to regulate signalling to the mother to allocate nutrients to the fetus,” added Professor Sferruzzi-Perri.

̽��ֱ��mice studied were smaller at birth and their offspring showed early signs of diabetes and obesity in later life.

Professor Sferruzzi-Perri said: “Our research highlights how important the controlled allocation of nutrients to the fetus is for the lifelong health of the offspring, and the direct role the placenta plays.

“ ̽��ֱ��placenta is an amazing organ. At the end of pregnancy, the placenta is delivered by the mother, but the memories of how the placenta was functioning leaves a lasting legacy on the way those fetal organs have developed and then how they’re going to function through life.”

̽��ֱ��next step is to understand how placental hormones are controlled by Igf2 and what those hormones are doing. Future research could help scientists discover new strategies to target the placenta to improve health outcomes for mums and babies.

Mice are used in research because the organisation of their DNA and their gene expression is similar to humans, with ninety-eight percent of human genes having a comparable gene in the mouse. They have similar reproductive and nervous systems to humans, and suffer from many of the same diseases such as obesity, cancer and diabetes.

Reference
Lopez-Tello, J et al. Fetal manipulation of maternal metabolism is a critical function of the imprinted Igf2 gene. Cell Metabolism; 11 July 2023; DOI: 10.1016/j.cmet.2023.06.007

Adapted from a press release from St John’s College Cambridge

A study in mice has found that fetuses use a copy of a gene inherited from their dad to force their mum to release as much nutrition as possible during pregnancy.

It’s the first direct evidence that a gene inherited from the father is signalling to the mother to divert nutrients to the fetus

Amanda Sferruzzi-Perri

Understanding Animal Research

Brown mouse

̽��ֱ��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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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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Scientists can predict which women will have serious pregnancy complications

Anonymous — Tue, 08 Jun 2021 16:01:04 +0000

Nearly all of the organ systems of the mother’s body need to alter their function during pregnancy so that the baby can grow. If the mother’s body cannot properly adapt to the growing baby this leads to major and common issues including fetal growth restriction, fetal over-growth, gestational diabetes, and preeclampsia – a life-threatening high blood pressure in the mother.

Many of these complications lead to difficult labours for women with more medical intervention and lifelong issues for the baby including diabetes, heart issues and obesity.

Pregnancy disorders affect around one in ten pregnant women, but current methods to diagnose them are not sensitive or reliable enough to identify all at-risk pregnancies.

Now scientists have found a way to test hormone levels in the placenta to predict which women will have serious pregnancy complications. Their study is published today in the journal Nature Communications Biology.

“We found that hormonal biomarkers from the placenta could indicate which women would have pregnancy complications,” said Dr Amanda Sferruzzi-Perri in the ̽��ֱ�� of Cambridge’s Department of Physiology, Development and Neuroscience, who led the study.

She added: “We found that these hormonal biomarkers are present from the first trimester of pregnancy. This is a highly important finding given that pregnancy disorders affect around one in ten pregnant women and are often diagnosed too late, when the complications are already wreaking havoc on the mother’s body and the fetal development.”

Using mouse models, researchers looked at the proteins made by the placenta and compared them to blood samples from women who had uneventful pregnancies and those who developed gestational diabetes. ̽��ֱ��team developed new methods to isolate and study the endocrine cells in the mouse placenta because these cells are responsible for secreting hormones during pregnancy.

They profiled the placenta to identify the hormones that are secreted to create a comprehensive map of proteins in the mysterious organ. ̽��ֱ��mouse model map of hormonal proteins from the placenta was then compared with datasets from studies of the human placenta and pregnancy outcomes and researchers discovered a lot of biological overlap.

Dr Sferruzzi-Perri said: “We found that around a third of the proteins we identified changed in women during pregnancies with disorders. Using a small study to test if these placental proteins will have some clinical value, we also discovered that abnormal levels of hormones were present in the mother’s blood as early as the first trimester – week 12 of gestation – in women who developed gestational diabetes, a pregnancy complication usually diagnosed at 24-28 weeks.

“We also identified several specific transcription factors – proteins within the cell that turn on or off genes – that are likely to govern the production of placental hormones which have important implications for understanding how we may improve pregnancy outcomes.”

̽��ֱ��scientists explored whether these genetic biomarkers were detectable during pregnancy and used a study that tracked pregnancy outcomes in women at Addenbrooke’s Hospital in Cambridge. They found that blood samples showed these biomarkers in early pregnancy which could lead to earlier diagnosis of complications allowing treatment to begin more quickly.

Dr Claire Meek, a diabetes in pregnancy physician and researcher at Addenbrooke’s, said: “This pregnancy-induced form of diabetes causes accelerated growth of the baby and complications at the time of delivery. Unfortunately, some women already have signs of a big baby at the time of diagnosis at 28 weeks. This new test might be able to identify gestational diabetes earlier in pregnancy, providing opportunities to prevent the disease, or to protect mums and babies from the most harmful complications.”

Dr Sferruzzi-Perri said: “This work provides new hope that a better understanding of the placenta will result in safer, healthier pregnancies for mothers and babies. Our team is now working to assess whether these discoveries could improve clinical care in future, either through earlier diagnosis or to provide new opportunities to treat these pregnancy complications by targeting the placenta.”

̽��ֱ��placenta is a complex biological organ. It forms and grows from the fertilised egg, and attaches to the wall of the uterus. It allows nutrients and oxygen to flow from mother to baby, and removes fetal waste products. Despite its importance, the placenta is a very misunderstood organ and is notoriously difficult to study in pregnant women. But its ability to function properly is vital as it impacts on pregnancy outcomes and the lifelong health of mother and child.

̽��ֱ��placenta develops during pregnancy and connects the developing baby to the mother. It serves as the lungs, kidneys, gut and liver for growing babies and carries oxygen and nutrients to the fetus whilst secreting hormones and discarding waste.

Reference

Napso, T. et al. Placental secretome characterization identified candidates for pregnancy complications. Nature Communications Biology, June 2021. DOI: https://doi.org/10.1038/s42003-021-02214-x

Adapted from a press release by St John's College, Cambridge

Women who will develop potentially life-threatening disorders during pregnancy can be identified early when hormone levels in the placenta are tested, a new study has shown.

This work provides new hope that a better understanding of the placenta will result in safer, healthier pregnancies for mothers and babies.

Amanda Sferruzzi-Perri

Fishman64 at Shutterstock.com

Pregnancy scan

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Placenta changes could mean male offspring of older mums more likely to develop heart problems in later life, rat study finds

jg533 — Thu, 28 Nov 2019 10:51:48 +0000

Both male and female fetuses do not grow as large in older mothers, but there are sex-specific differences in changes to placental development and function. These are likely to play a central role in the increased likelihood of later-life heart problems and high blood pressure in males.

In humans, women over 35 are considered to be of advanced maternal age. ̽��ֱ��study, published in Scientific Reports, looked at pregnant rats of a comparable age. In aged mothers, the placenta of female fetuses showed beneficial changes in structure and function that would maximise the support of fetal growth. In some instances, the placenta even supported the female fetus better than the placenta of a younger mother. In the case of male fetuses however, the placenta showed changes that would limit fetal growth in the aged pregnant rats.

“This new understanding of placental development and function could contribute to better management of human pregnancies, and development of targeted interventions to improve the longer-term health of children born to older mothers,” said Dr Tina Napso, a postdoctoral fellow at the ̽��ֱ�� of Cambridge and first author of the study.

Pregnancy in older mothers is associated with a heightened risk of complications for both the mother and her baby. These include preeclampsia - raised blood pressure in the mother during pregnancy, gestational diabetes, stillbirth and fetal growth restriction. Until now there has been limited understanding of how the placenta is altered by advanced maternal age.

“With the average age of first pregnancy in women becoming higher and higher, and especially so in developed countries, it is very important to understand how the age of the mother and the sex of the baby interact to determine pregnancy and later-life health of the child,” said Dr Amanda Sferruzzi-Perri, lead author of the study and a Royal Society Fellow in the Centre for Trophoblast Research at the ̽��ֱ�� of Cambridge’s Department of Physiology, Development and Neuroscience.

̽��ֱ��placenta transports nutrients and oxygen from mother to fetus, secretes signalling factors into the mother so she supports fetal development, and is the main protective barrier for the fetus against toxins, bacteria, and hormones - such as stress hormones - in the mother’s blood. It is highly dynamic in nature, and its function can change to help protect the growing fetus when conditions become less favourable for its development, for example through a lack of nutrients or oxygen or when the mother is stressed.

̽��ֱ��researchers analysed the placentas of young (3-4 months old) and aged rats (9.5-10 months old) that were pregnant with male and female offspring. ̽��ֱ��aged rats correspond to approximately 35 year-old humans. Rats are a useful model as their biology and physiology have a number of important characteristics in common with those of humans.

̽��ֱ��study found that advanced maternal age reduced the efficiency of the placenta of both male and female fetuses. It affected the structure and function of the placenta more markedly for male fetuses, reducing its ability to support growth of the fetus.

“A pregnancy at an older age is a costly proposition for the mother, whose body has to decide how nutrients are shared with the fetus. That’s why, overall, fetuses do not grow sufficiently during pregnancy when the mother is older compared to when she is young,” said Dr Napso. “We now know that growth, as well as gene expression in the placenta is affected in older mothers in a manner that partially depends on sex: changes in the placentas of male fetuses are generally detrimental.”

̽��ֱ��research involved a collaboration between scientists at the ̽��ֱ�� of Cambridge, the ̽��ֱ�� of Alberta in Canada, the Robinson Research Institute and the ̽��ֱ�� of Adelaide, Australia.

An earlier study performed by the collaborators showed that offspring from mothers who enter pregnancy at an older age have poor heart function and high blood pressure as young adults, and particularly so if they are male. This new research was conducted to understand why, and whether this sex difference may be due to how the male and female fetuses are supported within the womb in an aged mother.

Although further studies in humans are required, the results suggest the importance of considering the sex of the fetus when giving advice to older pregnant women. ̽��ֱ��researchers also hope to build on these results and find ways of improving the function of the placenta to optimise growth of the fetus.

Reference
Napso, T. et al: “Advanced maternal age compromises fetal growth and induces sex-specific changes in placental phenotype in rates.” Scientific Reports (2019). DOI:10.1038/s41598-019-53199-x

Changes occur in the placenta in older pregnant mothers leading to a greater likelihood of poor health in their male offspring, a study in rats has shown.

With the average age of first pregnancy in women becoming higher and higher, especially in developed countries, it is very important to understand how the age of the mother and the sex of the baby interact to determine pregnancy and later-life health of the child.

Amanda Sferruzzi-Perri

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Exercise in pregnancy improves health of obese mothers by restoring their tissues, mouse study finds

cjb250 — Thu, 29 Aug 2019 23:17:07 +0000

Researchers at the ̽��ֱ�� of Cambridge, who led the study published today in the journal Physiological Reports, say the findings reinforce the importance of an active lifestyle when planning pregnancy.

In the UK, more than a half of all women of reproductive age and almost a third of pregnant women are overweight or obese. This is particularly concerning, as being overweight or obese during pregnancy increases the risk of complications in the mother, such as gestational diabetes, and predisposes both her and her infant to develop metabolic diseases such as type 2 diabetes in the years after pregnancy.

Exercise is known to improve how the body manages blood sugar levels and thereby reduce the risk of type-2 diabetes and metabolic syndrome in non-pregnant women. It also has positive effects prior to and during pregnancy, with beneficial outcomes for both mother and her child, preventing excessive gestational weight gain and the development of gestational diabetes, and the need for insulin use in women who have already developed gestational diabetes. However, little is known about the changes that exercise causes to the tissues of obese pregnant mothers.

To answer this question, researchers at the ̽��ֱ�� of Cambridge fed mice a sugary, high fat diet such that they become obese and then the obese mice were exercised. ̽��ֱ��mice exercised on a treadmill for 20 minutes a day for at least a week before their pregnancy and then for 12.5 minutes a day until day 17 of the pregnancy (pregnancy lasts for around 20 days in mice).

Mice are a useful model for studying human disease as their biology and physiology have a number of important characteristics in common with those of humans, including showing metabolic changes with obesity/obesity-causing diets and in the female body during pregnancy.

̽��ֱ��researchers found that the beneficial effects on metabolic health in obese mothers related to changes in how molecules and cells communicate in maternal tissues during pregnancy.

“A moderate level of exercise immediately before and then during pregnancy leads to important changes in different tissues of the obese mother, effectively making the tissues more like those seen in non-obese mothers,” says Dr Amanda Sferruzzi-Perri, a Royal Society Dorothy Hodgkin Research Fellow from the Centre for Trophoblast Research in the Department of Physiology, Development and Neuroscience at the ̽��ֱ�� of Cambridge, who co-led the study.

“We believe these changes may explain how exercise improves the metabolism of the obese mother during pregnancy and, in turn, may prevent her babies from developing early signs of type 2 diabetes after birth.”

̽��ֱ��key organs of the mother that were affected by exercise were:

white adipose tissue – the fatty tissue that stores lipids and can be found in different parts around the body, including beneath the skin and around internal organs;
skeletal muscle – muscle tissue that uses glucose and fats for contraction and movement;
the liver – the organ that stores, as well as syntheses lipids and glucose.

Exercise affected key signalling pathways – the ways that molecules and cells within tissue communicate – involved in responding to insulin (the hormone that stimulates glucose uptake by white adipose tissue and skeletal muscle), in storage and breakdown of lipids (fats found in the blood and tissue) and in growth and the synthesis of proteins.

White adipose tissue showed the greatest number of changes in response to exercise in the obese pregnant mouse, being restored to a state similar to that seen in the tissue of non-obese mothers. This suggests that insulin resistance of the mother’s white adipose tissue may be the cause of poor glucose-insulin handling in obese pregnancies. ̽��ֱ��findings are different to that seen in non-pregnant animals, whereby exercise typically affects insulin signalling in the skeletal muscle.

In addition, the team’s previous work showed that exercise improves sensitivity to insulin and glucose handling throughout the whole body in the obese mother. It also prevents the development of insulin resistance in the offspring of obese mothers after birth. Low insulin sensitivity/insulin resistance requires larger amounts of insulin to control blood glucose levels.

“Our findings reinforce the importance of having an active lifestyle and eating a healthy balanced diet when planning pregnancy and throughout for both the mother and her developing child,” says co-lead Professor Susan Ozanne from the Wellcome Trust-Medical Research Council Institute of Metabolic Science at the ̽��ֱ�� of Cambridge.

“This can be important in helping to reduce the risk of adverse health problems in the mother and of later health problems for her child.”

This work received funding from the European Union, Medical Research Council, Biotechnology and Biological Sciences Research Council, British Heart Foundation, São Paulo Research Foundation, Centre for Trophoblast Research, and the Royal Society.

Reference
Musial, B et al. Exercise alters the molecular pathways of insulin signalling and lipid handling in maternal tissues of obese pregnant mice. Physiological Reports; 28 August 2019; DOI: 10.14814/phy2.14202

Exercise immediately prior to and during pregnancy restores key tissues in the body, making them better able to manage blood sugar levels and lowering the risk of long term health problems, suggests new research carried out in mice.

A moderate level of exercise immediately before and then during pregnancy leads to important changes in different tissues of the obese mother, effectively making the tissues more like those seen in non-obese mothers

Amanda Sferruzzi-Perri

ArtCoreStudios (Pixabay)

Workout

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High fat, high sugar diet during pregnancy 'programs' for health complications in mother and child

tdk25 — Thu, 06 Apr 2017 03:00:53 +0000

In a study carried out in pregnant mice, a team of academics found that an obesity-causing high fat and high sugar diet disrupted processes within the pregnant mother’s body, leading to poor metabolic control. These changes were found just prior to birth and may make her more susceptible to conditions such as type 2 diabetes and heart disease, as well as to further fat accumulation, in later motherhood.

̽��ֱ��exact impact on her child during pregnancy was harder to ascertain, but the researchers found that metabolic dysfunction in the mother compromised the flow of nutrients to the foetus, altering its growth and metabolism at critical stages during its development. This strongly suggests that an obesogenic diet (a diet which promotes obesity) also has consequences for foetal development. It may also explain why babies from mothers who are obese or eat obesogenic diets during pregnancy have a tendency to develop conditions such as obesity, hypertension and type 2 diabetes as adults.

In particular, the researchers found that a higher than recommended intake of fat and sugar exacerbates and distorts metabolic changes which occur naturally as a result of the pregnancy, so that the mother can appropriately allocate nutrients to the foetus.

̽��ֱ��study was carried out by a team of researchers at the ̽��ֱ�� of Cambridge. ̽��ֱ��lead author is Dr Amanda Sferruzzi-Perri, from St John’s College, Cambridge, and the Centre for Trophoblast Research in the Department of Physiology, Development and Neuroscience. She said that the findings were especially relevant for women in western countries.

“In places like the UK, the US and Australia, many women of child-bearing age are also eating higher amounts of fat and sugar than the National Dietary Recommendations,” she said. “We know that obesity during pregnancy is a risk factor for health complications for mother and baby both during and after pregnancy. This study offers insight into the mechanisms operating during pregnancy that may cause this.”

̽��ֱ��study involved feeding a diet that contained high amounts of fat and sugar to pregnant mice. ̽��ֱ��researchers then assessed the impact of this on both the metabolism of the mother and her levels of body fat, compared to mice which were fed a more balanced diet.

They related these changes in whole-body metabolism to the expression of proteins in the mother’s tissues, which are responsible for processing and storing nutrients, as well as to the supply of nutrients, growth and metabolism of her developing foetuses. All of the experiments were carried out in line with the UK Home Office Animals (Scientific Procedures) Act 1986.

Overall, the researchers found that excessive consumption of sugar and fat compromised the mother’s glucose tolerance and her sensitivity to insulin – the hormone that controls blood sugar levels.

Specifically, they found that the mother’s ability to respond to insulin was reduced in tissues like her muscle and fat, which take up glucose from the circulation. By contrast, the sensitivity of the maternal liver to insulin was increased, which reduces glucose production during pregnancy. As a result, the mother was unable adequately to control glucose levels or produce enough glucose to support the pregnancy.

̽��ֱ��high fat, high sugar diet also changed the expression of proteins in the mother’s body that control fat storage, leading to an increase in body fat. Collectively, the researchers suggest that these effects promote a “pre-diabetic state” in the mother, resembling many aspects of gestational diabetes; a pregnancy complication which affects up to 5% of women in the UK.

One of the main reasons for this may be that an obesogenic diet exaggerates natural metabolic changes associated with pregnancy. “During a normal pregnancy, the mother’s body will change the way it handles nutrients so that some can be freed up for the foetus,” Sferruzzi-Perri explained. “ ̽��ֱ��mother’s metabolism is shifted to an insulin resistant, glucose intolerant state, such that her own glucose use is limited in favour of foetal supply. We think that in cases where the mother has a high fat, high sugar diet, these metabolic changes are exacerbated or perturbed.”

These effects, the researchers suggest, may alter the mother’s disposition to develop health complications after she has given birth as well – a phenomenon that they refer to as a “metabolic memory”, putting her at greater risk of type 2 diabetes, obesity and cardiovascular problems in later life.

̽��ֱ��study also found that the defects in the mother’s metabolism impaired nutrient flow to the foetus, as they resulted in the preferential storage of nutrients within the mother’s tissues, in favour of allocating these to the developing foetus.

Because the placenta also plays an important role in nutrient allocation (as previous studies have shown), the babies of mice fed the obesogenic diet were still born at a normal size. However, because the foetus receives different amounts of nutrients and shows defects in its ability to use these during development, the researchers believe that the child will still be more susceptible to metabolic dysfunction later in life.

“We still don’t know what the exact consequences for the foetus are, but the findings match existing research which already suggests that the individual will suffer from these metabolic problems during adulthood,” Sferruzzi-Perri said. “This is because changes to the nutrient and oxygen supply, at a stage when individual organs are developing, can cause a permanent change in the structure and function of certain tissues.”

̽��ֱ��full study, A Western-style obesogenic diet alters maternal metabolic physiology with consequences for fetal nutrient acquisition in mice is published in ̽��ֱ��Journal of Physiology. DOI: 10.1113/JP273684.

Eating a high fat and high sugar diet when pregnant leads to metabolic impairments in both the mother and her unborn child, which may 'program' them for potential health complications later in life, a study in mice has shown.

We know that obesity during pregnancy is a risk factor for health complications for mother and baby both during and after pregnancy. This study offers insight into the mechanisms operating during pregnancy that may cause this.

Amanda Sferruzzi-Perri

Free image via Max Pixel

̽��ֱ��researchers found that a high fat and high sugar diet exaggerates metabolic changes in the mother which occur naturally during pregnancy, potentially rendering her more susceptible to health complications.

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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Placenta plays pivotal “umpire” role to influence pregnancy outcomes

tdk25 — Mon, 12 Sep 2016 19:00:56 +0000

Researchers have shown for the first time how the placenta “umpires” a fight for nutrients between a pregnant mother and her unborn baby. ̽��ֱ��study suggests that the placenta will adjust the amount of nutrients transported to the foetus for growth in line with the mother’s physical ability to supply.

̽��ֱ��findings, published in the journal PNAS, suggest that if the bodily environment that a mother provides for her baby is unfavourable, for example through small body size or metabolic dysfunction, the placenta will change the flow of nutrients to the foetus relative to her own state. This can affect foetal development, resulting in complications at birth.

It is the first time that scientists have been able to provide clear evidence that the placenta plays the decisive role in this delicate balancing act, rather than merely acting as a passive interface which enables the transfer of nutrients from mother to foetus.

̽��ֱ��study, by researchers at the ̽��ֱ�� of Cambridge, involved making a precise genetic change in mice, which caused poor growth and changed the mother’s bodily environment. They then observed how the placenta developed and acted in response, finding that in mothers in which this alteration had been made, the structure of the placenta was different, and fewer nutrients reached the foetus.

A better understanding of how the placenta manages the trade-off will eventually enable researchers to reduce pregnancy complications in both humans and other mammals.

̽��ֱ��study was led by Dr Amanda Sferruzzi-Perri, a Research Associate at St John’s College, ̽��ֱ�� of Cambridge, and is part of a five-year project in the Department of Physiology, Development and Neuroscience examining the relationship between the placenta and pregnancy complications.

“During pregnancy there is a kind of ‘tug-of-war’ going on between the mother and the foetus over who gets the nutrients that the mother ingests,” Sferruzzi-Perri said. “This work shows for the first time that the placenta is the umpire which controls that fight. Understanding more about the placenta’s role is extremely important. If nutrients cannot be divided correctly during pregnancy, it can lead to life-threatening complications for expectant mothers, and long-term health consequences for both mother and child.”

At least one in every eight pregnancies in the UK is affected by complications stemming from impairment of the placenta. In the developing world the rate is even higher, with at least one in every five pregnant women affected. ̽��ֱ��potential consequences include abnormal birth weight, premature delivery, pre-eclampsia, and maternal diabetes.

A major cause appears to be the placenta’s response to unfavourable biological changes in the mother herself. These may, for example, be the result of poor nutrition, high stress levels, metabolic dysfunction, or obesity.

How the placenta allocates nutrients in these situations, however, and the hormonal signals that the placenta may be releasing while doing so, is not fully understood. By understanding these processes better, researchers hope to identify both the biological early warning signals that a problem has arisen, and their relationship to specific causes, enabling them to develop therapeutic interventions that reduce the number of complications overall.

̽��ֱ��new study represents a step towards those aims because researchers were able to directly influence the balancing act that the placenta performs and observe it in relation to both the physiology of the mother, and the actual growth and nutrient supply of the foetus.

To achieve this they used a model system where an enzyme called p110 alpha was genetically modified in mice. In a healthy mother, this enzyme is activated by hormones like insulin and insulin-growth factors (IGFs), kick-starting a relay race within cells which stimulates nutrient uptake and, as a result, normal growth and metabolic function. By altering this enzyme, the team reduced the mother’s overall responsiveness to such hormones, creating an unfavourable environment.

̽��ֱ��results showed that in mothers which carried the altered form of p110 alpha, the placenta’s growth and structure was impaired. As well as being physically different, it was also found to be transporting fewer nutrients to the unborn offspring.

Because of the way in which the experiments were set up, the team were also able to see what would happen to the placenta if the foetus carried the altered form of p110 alpha, but the mother was normal. They found that in these cases, the placenta also showed defects, but was able to compensate for this by transporting more nutrients to the foetus, and thus optimising nutrition.

This shows that the placenta will fine-tune the distribution of nutrients between the mother and foetus, in response to the circumstances in which it finds itself. It also indicates that, because the mother needs to be able to support her baby both during pregnancy and after birth, the placenta will do its best to judge how much nutrition the foetus receives, so that the mother’s health is not compromised.

“ ̽��ֱ��placenta is taking in signals all the time from the mother and the foetus,” Sferruzzi-Perri explained. “If the mother has some sort of defect in her ability to grow, the placenta will limit the amount of nutrients it allocates to the foetus to try and preserve her health.”

“What this tells us is that the mother’s environment is a very strong, modifiable characteristic to which we should be paying more attention, in particular to see if there are specific factors that we can change to improve the outcome of pregnancies. Being able to influence the mother’s environment through changes in p110 alpha gives us a means to study this in a controlled way, and to work out what those critical factors are.”

̽��ֱ��next stage of the research will involve examining the signals that the placenta sends to the mother to affect the way she uses the nutrients she ingests, potentially providing important clues about biomarkers which provide an early warning of pregnancy complications.

Dr Sferruzzi-Perri’s research is supported by a Dorothy Hodgkin Fellowship from the Royal Society. Her paper, Maternal and fetal genomes interplay through phosphoinositol 3-kinase(PI3K)-p110α signalling to modify placental resource allocation, is published in PNAS. ̽��ֱ��work was supported by a Next Generation Fellowship from the Centre for Trophoblast Research.

New research provides the first clear evidence that the amount of nutrients transported to the foetus by the placenta adjusts according to both the foetal drive for growth, and the mother’s physical ability to provide.

During pregnancy there is a kind of ‘tug-of-war’ going on between the mother and the foetus over who gets the nutrients that the mother ingests. This work shows for the first time that the placenta is the umpire which controls that fight

Amanda Sferruzzi-Perri

Free stock image via Pexels.

"Pregnant".

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. For image use please see separate credits above.

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