Exposure to air pollution while in the womb is linked to adverse changes in cell processes in new-born babies

Exposure to air pollution while in the womb is linked to alterations in proteins that can be detected after a baby is born, and which affect cell processes such as autophagy, the "self-eating" of damaged cells that occurs in response to stress.

Dr Olga Gorlanova, a research physician at the University Children's Hospital, University of Basel, Switzerland, told the European Respiratory Society International Congress in Milan, Italy, that her study also showed that healthy, new-born babies had individual and different responses to their mothers' exposure to air pollution during pregnancy. This might mean that some babies were more vulnerable to it than others. This was the case even if they were born into households in areas with relatively low levels of pollution.

Earlier work by Dr Gorlanova and her colleagues had shown that exposure to air pollution during pregnancy could affect lung function and the immune system in new-borns. In the current study, they looked at proteins involved in autophagy, ageing and cell remodelling to see how prenatal exposure to air pollution could affect them.

The researchers measured 11 proteins found in the cord blood of 449 healthy new-born babies from the Bern Basel Infant Lung Development (BILD) cohort study. The BILD study, started in 1999 in Bern, aims to recruit 1000 babies by 2025. It is investigating the effects of genetics and the environment (particularly air pollution) on lung development in babies and children.

Dr Gorlanova and colleagues measured the mothers' exposure to nitrogen dioxide (NO2) and tiny particles called PM10,which areparticulate matter measuring 10 microns or less in diameter. Vehicle emissions, tyre and brake wear, and smoke are some of the sources of these pollutants. They found that NO2 and PM10 were both linked to changes in proteins involved in autophagy. Exposure to NO2 was linked to a decrease in the activity of the proteins SIRT1 and IL-8, and an increase in levels of the Beclin-1 protein.

"Our results indicate that NO2, a pollutant formed mainly from traffic emissions, is associated with increased levels of Beclin-1 protein, which is central to initiating autophagy. Exposure to higher NO2 was also linked to decreased levels of SIRT1, which is a protein that plays a protective role in stress resistance, inflammation and aging. IL-8 is a protein active in certain inflammatory cells," said Dr Gorlanova.

"We grouped the babies into four distinct clusters according to the levels of air pollution they were exposed to while in the womb. The four clusters all had similar concentrations of the proteins being studied but had differences their exposure to NO2 and PM10 air pollution. One cluster had low concentrations of nine proteins, while another cluster, consisting of seven percent of all the babies, had higher levels of proteins that are involved in inflammatory and remodelling processes: IL-8 and IL-1B. Both these groups of new-borns had been exposed to lower, although differing, levels of prenatal air pollution than the other two groups. Our findings suggest that healthy new-borns have an individual response pattern to air pollution. We think that this may be an indication that some babies are more vulnerable to it than others.

"Additionally, our work adds to the growing body of evidence that autophagy-related mechanisms may be involved in how human cells react to air pollution. The findings are consistent with evidence from tissue and animal research. Further exploration of these mechanisms may help to better understand the deleterious effects of pollution on infants."

The researchers plan to examine whether babies with distinct protein response patterns to air pollution will suffer from more breathing problems during infancy and childhood compared to those that do not show the same protein responses.

Professor Marielle Pijnenburg, associate professor of pediatric pulmonology and head of the Department of Pediatric Respiratory Medicine and Allergology at Erasmus Medical Center, Rotterdam, The Netherlands, is head of the ERS group on paediatrics and was not involved with the research. She commented: "This study adds to the growing body of evidence that air pollution can affect the health of children before and after they are born. It contributes to other research showing that autophagy-related mechanisms may be involved in how human cells react to air pollution. We need to know more about how these mechanisms can affect the health of lungs, and we need to understand why some new-borns seem to be more susceptible to air pollution than others.

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Babies react to taste and smell in the womb

Scientists have recorded the first direct evidence that babies react differently to various smells and tastes while in the womb by looking at their facial expressions.

A study led by Durham University's Fetal and Neonatal Research Lab, UK, took 4D ultrasound scans of 100 pregnant women to see how their unborn babies responded after being exposed to flavours from foods eaten by their mothers.

Researchers looked at how the fetuses reacted to either carrot or kale flavours just a short time after the flavours had been ingested by the mothers.

Fetuses exposed to carrot showed more "laughter-face" responses while those exposed to kale showed more "cry-face" responses.

Their findings could further our understanding of the development of human taste and smell receptors.

The researchers also believe that what pregnant women eat might influence babies' taste preferences after birth and potentially have implications for establishing healthy eating habits.

The study is published in the journal Psychological Science.

Humans experience flavour through a combination of taste and smell. In fetuses it is thought that this might happen through inhaling and swallowing the amniotic fluid in the womb.

Lead researcher Beyza Ustun, a postgraduate researcher in the Fetal and Neonatal Research Lab, Department of Psychology, Durham University, said:

"A number of studies have suggested that babies can taste and smell in the womb, but they are based on post-birth outcomes while our study is the first to see these reactions prior to birth.

"As a result, we think that this repeated exposure to flavours before birth could help to establish food preferences post-birth, which could be important when thinking about messaging around healthy eating and the potential for avoiding 'food-fussiness' when weaning.

"It was really amazing to see unborn babies' reaction to kale or carrot flavours during the scans and share those moments with their parents."

The research team, which also included scientists from Aston University, Birmingham, UK, and the National Centre for Scientific Research-University of Burgundy, France, scanned the mothers, aged 18 to 40, at both 32 weeks and 36 weeks of pregnancy to see fetal facial reactions to the kale and carrot flavours.

Mothers were given a single capsule containing approximately 400mg of carrot or 400mg kale powder around 20 minutes before each scan. They were asked not to consume any food or flavoured drinks one hour before their scans.

The mothers also did not eat or drink anything containing carrot or kale on the day of their scans to control for factors that could affect fetal reactions.

Facial reactions seen in both flavour groups, compared with fetuses in a control group who were not exposed to either flavour, showed that exposure to just a small amount of carrot or kale flavour was enough to stimulate a reaction.

Co-author Professor Nadja Reissland, head of the Fetal and Neonatal Research Lab, Department of Psychology, Durham University, supervised Beyza Ustun's research. She said:

"Previous research conducted in my lab has suggested that 4D ultrasound scans are a way of monitoring fetal reactions to understand how they respond to maternal health behaviours such as smoking, and their mental health including stress, depression, and anxiety.

"This latest study could have important implications for understanding the earliest evidence for fetal abilities to sense and discriminate different flavours and smells from the foods ingested by their mothers."

Co-author Professor Benoist Schaal, of the National Centre for Scientific Research-University of Burgundy, France, said:

"Looking at fetuses' facial reactions we can assume that a range of chemical stimuli pass through maternal diet into the fetal environment.

"This could have important implications for our understanding of the development of our taste and smell receptors, and related perception and memory."

The researchers say their findings might also help with information given to mothers about the importance of taste and healthy diets during pregnancy.

They have now begun a follow-up study with the same babies post-birth to see if the influence of flavours they experienced in the womb affects their acceptance of different foods.

Research co-author Professor Jackie Blissett, of Aston University, said:

"It could be argued that repeated prenatal flavour exposures may lead to preferences for those flavours experienced postnatally. In other words, exposing the fetus to less 'liked' flavours, such as kale, might mean they get used to those flavours in utero.

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‘Battle of the sexes’ begins in womb as father and mother’s genes tussle over nutrition

Cambridge scientists have identified a key signal that the fetus uses to control its supply of nutrients from the placenta, revealing a tug-of-war between genes inherited from the father and from the mother. The study, carried out in mice, could help explain why some babies grow poorly in the womb.

As the fetus grows, it needs to communicate its increasing needs for food to the mother. It receives its nourishment via blood vessels in the placenta, a specialised organ that contains cells from both baby and mother.

Between 10% and 15% of babies grow poorly in the womb, often showing reduced growth of blood vessels in the placenta. In humans, these blood vessels expand dramatically between mid and late gestation, reaching a total length of approximately 320 kilometres at term.

In a study published today in Developmental Cell, a team led by scientists at the University of Cambridge used genetically engineered mice to show how the fetus produces a signal to encourage growth of blood vessels within the placenta. This signal also causes modifications to other cells of the placenta to allow for more nutrients from the mother to go through to the fetus.

Dr Ionel Sandovici, the paper's first author, said: "As it grows in the womb, the fetus needs food from its mum, and healthy blood vessels in the placenta are essential to help it get the correct amount of nutrients it needs.

"We've identified one way that the fetus uses to communicate with the placenta to prompt the correct expansion of these blood vessels. When this communication breaks down, the blood vessels don't develop properly and the baby will struggle to get all the food it needs."

The team found that the fetus sends a signal known as IGF2 that reaches the placenta through the umbilical cord. In humans, levels of IGF2 in the umbilical cord progressively increase between 29 weeks of gestation and term: too much IGF2 is associated with too much growth, while not enough IGF2 is associated with too little growth. Babies that are too large or too small are more likely to suffer or even die at birth, and have a higher risk to develop diabetes and heart problems as adults.

Dr Sandovici added: "We've known for some time that IGF2 promotes the growth of the organs where it is produced. In this study, we've shown that IGF2 also acts like a classical hormone -- it's produced by the fetus, goes into the fetal blood, through the umbilical cord and to the placenta, where it acts."

Particularly interesting is what their findings reveal about the tussle taking place in the womb.

In mice, the response to IGF2 in the blood vessels of the placenta is mediated by another protein, called IGF2R. The two genes that produce IGF2 and IGF2R are 'imprinted' -- a process by which molecular switches on the genes identify their parental origin and can turn the genes on or off. In this case, only the copy of the igf2 gene inherited from the father is active, while only the copy of igf2r inherited from the mother is active.

Lead author Dr Miguel Constância, said: "One theory about imprinted genes is that paternally-expressed genes are greedy and selfish. They want to extract the most resources as possible from the mother. But maternally-expressed genes act as countermeasures to balance these demands."

"In our study, the father's gene drives the fetus's demands for larger blood vessels and more nutrients, while the mother's gene in the placenta tries to control how much nourishment she provides. There's a tug-of-war taking place, a battle of the sexes at the level of the genome."

The team say their findings will allow a better understanding of how the fetus, placenta and mother communicate with each other during pregnancy. This in turn could lead to ways of measuring levels of IGF2 in the fetus and finding ways to use medication to normalise these levels or promote normal development of placental vasculature.

The researchers used mice, as it is possible to manipulate their genes to mimic different developmental conditions. This enables them to study in detail the different mechanisms taking place. The physiology and biology of mice have many similarities with those of humans, allowing researchers to model human pregnancy, in order to understand it better.

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