Tag: in utero effects

Study Shows that Probiotics in Pregnancy Benefit Mothers and Offspring

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Giving probiotics to pregnant mice can enhance both the immune system and behaviour of the mothers and their offspring, according to a new study led by The Ohio State University Wexner Medical Center and College of Medicine.

“These results suggest that certain probiotics given to mothers during pregnancy can improve their offsprings’ behaviour and may affect the metabolism of common amino acids in our diets. Probiotics may also help counteract the negative effects of prenatal stress,” said study senior author Tamar Gur, MD, PhD, at OSU. 

Study findings are published online in the journal Brain, Behavior, and Immunity

Many studies have attested to the benefits of probiotics, which are considered safe to take during pregnancy. Researchers led by first author Jeffrey Galley, PhD found that a specific probiotic, Bifidobacterium dentium, may change how the body processes certain amino acids, such as tryptophan. During pregnancy, tryptophan helps control inflammation and brain development. 

“We have strong evidence this specific probiotic helped reduce stress-related problems in both mothers and their offspring, including helping the babies gain weight and improving their social behaviour,” said Gur, who also is an associate professor of psychiatry, neuroscience and obstetrics and gynaecology at Ohio State. 

Gur’s research team has studied how prenatal stress can lead to abnormal brain development and behavioural changes in offspring. So far, they’ve found that stress is linked to changes in brain inflammation and amino acid metabolism, as well as long-term reductions in social behaviour and abnormal microbiomes in offspring.

This study enhances their understanding of how gut microbes and probiotics can influence amino acid metabolism and help with behaviour and immune issues related to prenatal stress. The study also highlights the many benefits of this specific probiotic, even without the presence of stress.

“Now, we aim to understand the mechanisms behind these changes and explore ways to prevent or treat these effects,” Gur said. “Since prenatal stress is common in many pregnancies, we want to develop methods to reduce its negative effects.”

Source: Ohio State University Wexner Medical Center

Fatty Acids in Umbilical Cord Blood Might Cause Autism Spectrum Disorder

Scientists unveil the link between cord blood fatty acid metabolites and autism spectrum disorder symptoms in children

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Autism spectrum disorder (ASD) is quite prevalent, but its underlying mechanism is not well understood. In a recent study, researchers from Japan have found a significant link between the levels of specific dihydroxy fatty acids in umbilical cord blood and ASD symptoms. Their findings, published in Psychiatry and Clinical Neurosciences, highlight the role of these metabolites in the developmental trajectory of ASD and could pave the way for early diagnostic techniques and a better understanding of ASD pathophysiology.

Although the exact causes of ASD are unclear, currently available evidence points to neuroinflammation as a major factor. Several studies in mouse models of ASD have hinted at the importance of polyunsaturated fatty acids (PUFA) and their metabolites during pregnancy in playing a key role in ASD development. PUFA metabolites regulated by the cytochrome P450 (CYP) affect foetal development in mice causing impairments closely linked to ASD symptoms. However, it is still unclear if the same is true for humans and needs further investigation.

To address this knowledge gap, a research team led by Professor Hideo Matsuzaki from the Research Center for Child Mental Development, analysed the CYP-PUFA levels in neonatal umbilical cord blood samples. Their study,  sheds light on the possible causes of ASD.

Sharing the motivation behind their study, Prof. Matsuzaki explains, “CYP metabolism forms both epoxy fatty acids (EpFAs), which have anti-inflammatory effects, and dihydroxy fatty acids, or ‘diols,’ which have inflammatory properties. We hypothesized that the dynamics of CYP-PUFA metabolites during the fetal period, that is, lower EpFA levels, higher diol levels, and/or increased EpFA metabolic enzymes would influence ASD symptoms and difficulties with daily functioning in children after birth.”

To test this hypothesis, the researchers investigated the link between PUFA metabolites in umbilical cord blood and ASD scores in 200 children. The cord blood samples had been collected immediately after birth and preserved appropriately, whereas ASD symptoms and adaptive functioning were assessed when the same children were six years old, with the help of their mothers.

After careful statistical analyses of the results, the researchers identified one compound in cord blood that may have strong implications for ASD severity, namely 11,12- dihydroxyeicosatrienoic acids (diHETrE), a dihydroxy fatty acid derived from arachidonic acid. This fatty acid is found in poultry, animal organs and meat, fish, seafood, and eggs.

“The levels of diHETrE, an arachidonic acid-derived diol, in cord blood at birth significantly impacted subsequent ASD symptoms in children and were also associated with impaired adaptive functioning. These findings suggest that the dynamics of diHETrE during the foetal period is important in the developmental trajectory of children after birth,” highlights Prof Matsuzaki.

More specifically, the researchers found that higher levels of the molecule 11,12-diHETrE had an impact on social interactions, whereas low levels of 8,9-diHETrE impacted repetitive and restrictive behaviours. Moreover, this correlation was more specific for girls than for boys. This newfound knowledge could be crucial in understanding, diagnosing, and potentially preventing ASD. By measuring diHETrE levels at birth, it may be possible to predict the likelihood of ASD development in children.

“The effectiveness of early intervention for children with ASD is well established and detecting it at birth could enhance intervention and support for children with ASD,” muses Prof Matsuzaki. He also adds that inhibiting diHETrE metabolism during pregnancy might be a promising avenue for preventing ASD traits in children, although more research will be needed in this regard.

In conclusion, these findings open a promising avenue for researchers unravelling the mysteries surrounding ASD. We hope that enhanced understanding and early diagnostics will be able to improve the lives of people with ASD and their families.

Source: University of Fukui

Adolescent Behaviour Problems and In Utero Cannabis Exposure: A Biological Link

More evidence shows potential connection between cannabis exposure in womb and adolescent behavioural problems

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Scientists are trying to understand how cannabis may affect long-term neurodevelopment from in utero exposure. Previous work by Washington University in St. Louis researchers Sarah Paul and David Baranger in the Behavioral Research and Imaging Neurogenetics (BRAIN) lab led by Ryan Bogdan found associations between prenatal cannabis exposure and potential mental health conditions in childhood and adolescence, but potential biological mechanisms that could possibly explain this association were unclear.

In research published in Nature Mental Health this month, Bogdan, professor of psychological and brain sciences, and senior scientist Baranger outline some of those potential mechanisms, the intermediate biological steps that could play into how prenatal cannabis exposure leads to behavioural issues down the line.

“We see evidence that cannabis exposure may influence the developing brain, consistent with associations with mental health,” Baranger said.

Trying to draw out the long-term impacts of cannabis exposure during pregnancy is not a simple knot to untangle. There are many confounding factors that affect mental health and behavior.

For example, say someone was exposed in utero to cannabis and later develops attention deficit disorder as a teen – how do you differentiate that as an inherited trait or a trait influenced by environmental factors, versus a trait that cannabis exposure somehow contributed to early on in development? It is also possible that all three potentially could contribute to eventual psychopathology.

Another complication is the increasing prevalence of the drug, including among the pregnant population, where cannabis use has increased from 3% to 7% from 2002 to 2017.

Researchers have statistical methods to filter out some of those confounding factors that they used in the previous study, but now they can point to specific biological measurements that further signal a connection to cannabis exposure and adolescent behavioral problems.

Bogdan said that nothing can establish causation with certainty, “but we can look at the plausibility of causation and identifying biological correlates that are associated with exposure and these mental health outcomes suggests it’s plausible.”

Researchers have been using data on the children and their mothers from the Adolescent Brain and Cognitive Development (ABCD) Study, an ongoing research project that includes nearly 12 000 children across the country. As part of that study, they collected data about each mother’s substance use prior to the birth as well as the neuroimaging data of their offspring when they were between 9 and 10 and 11 and 12 years old. Some 370 children were exposed to cannabis prior to the mother’s knowledge of pregnancy, and 195 were exposed before and after learning of pregnancy.

The researchers looked at a variety of neuroimaging measurements that factor into brain development, including measures of brain thickness and surface area, as well as measures reflecting water diffusion in and outside of cells. The patterns found in the group exposed to cannabis are consistent with potential reductions in neuroinflammation.

“It’s possible what we’re seeing is an anti-inflammatory effect of cannabis, which is leading to differences in how the brain is being pruned during neurodevelopment,” Bogdan said.

Much has been touted about the anti-inflammatory effects of cannabis, but it’s not always good to reduce inflammation. It’s all about the timing: too much of a reduction of inflammation at the wrong time could affect how the brain is pruned and primed.

Another theory is that cannabis exposure leads to accelerated aging. But don’t expect to find the smoking gun of biological clues pinning mental health problems to early cannabis exposure.

It might not even be about cannabis effects on pruning but the post-combustion products from smoking cannabis that set off accelerated aging and the downstream cognitive effects, Bogdan said.

Or, it could all come down to sociological factors, he added.

Trying to find the one-to-one connection that proves that prenatal cannabis exposure has negative effects during the teenage years is a challenge and may not be possible with retrospective studies. Baranger notes that the major limitation of this data set is that it was retrospective; mothers reported what their cannabis use was 10 years ago, so he’s looking forward to new data from prospective, longitudinal studies that will offer more recent, accurate and detailed information about cannabis use in pregnancy.

“That will potentially give us more answers to these questions in the future,” Baranger said.

Baranger said these results reaffirm that if someone is thinking about using cannabis while pregnant, they should “talk to their doctor about their choices and what other options there might be.”

Source: Washington University in St. Louis

Exercising during Pregnancy Normalises Eating Behaviours in Offspring from Obese Mice

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Maternal obesity impacts the eating behaviours of offspring via long-term overexpression of the microRNA miR-505-5p, according to a study publishing June 4 in the open-access journal PLOS Biology by Laura Dearden and Susan Ozanne from the MRC Metabolic Diseases Unit, Institute of Metabolic Science, University of Cambridge, UK, and colleagues.

Previous studies in both humans and animal models have shown that the offspring of obese mothers have a higher risk of obesity and type 2 diabetes.

While this relationship is likely the result of a complex relationship between genetics and environment, emerging evidence has implicated that maternal obesity can disrupt the hypothalamus – the region of the brain responsible for nutrition sensing and energy homeostasis.

In animal models, offspring exposed to overnutrition during key periods of development eat more, but little is known about the molecular mechanisms that lead to these changes in eating behaviour.

In this study, researchers found that mice born from obese mothers had higher levels of the microRNA miR-505-5p in their hypothalamus – from as early as the foetal stage into adulthood.

The researchers found that the mice ate more and showed a preference for high-fat foods.

Interestingly, the effect of maternal obesity on miR-505-5p and eating behaviours was mitigated if the mothers exercised during pregnancy.

Cell culture experiments showed that miR-505-5p expression could be induced by exposing hypothalamic neurons to long-chain fatty acids and insulin, which are both high in pregnancies complicated by obesity.

The researchers identified miR-505-5p as a novel regulator of pathways involved in fatty acid uptake and metabolism, therefore high levels of the miRNA make the offspring brain unable to sense when eating high fat foods.

Several of the genes that miR-505-5p regulates have been associated with high body mass index in human genetic studies.

The study is one of the first to demonstrate the molecular mechanism linking nutritional exposure in utero to eating behaviour.

The authors add, “Our results show that obesity during pregnancy causes changes to the baby’s brain that makes them eat more high fat food in adulthood and more likely to develop obesity. Importantly we showed that moderate exercise, without weight loss, during pregnancies complicated by obesity prevented the changes to the baby’s brain. This helps us understand why the children of mothers living with obesity are more likely to become obese themselves, with early life exposures, genetics and current environment all being contributing factors.”

Provided by PLOS