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Maternal obesity can affect foetal development

by University of the Basque Country

Credit matthew-wiebe---B8vV-I3SE-unsplash.jpg

Placental DNA methylation may be one of the mechanisms by which maternal obesity is associated with adverse metabolic health outcomes in childhood, although further studies would be needed to corroborate these findings.

FAB RESEARCH COMMENT:

Obesity in mothers before and during pregnancy is now extremely common, and has long been known to predict disadvantageous outcomes for the resulting children - including:

  • Higher risks for childhood obesity, Type 2 diabetes and related 'metabolic' conditions
  • Higher risks for a wide range of childhood behaviour and learning difficulties 
The precise mechanisms by which maternal obesity affects the unborn child remain unclear (and are of course extremely complex!)

However, a good deal is already known about 'nutritional programming' - the name given to the many ways in which some aspects of nutrition in early life can permanently alter gene expression.

And one common way in which nutrition can alter gene expression is via 'methylation' - i.e. the addition of a 'methyl group' (a small chemical unit made up of carbon and oxygen atoms) to DNA. 

And as the lead author of this new study explains in this news artcle - methylation can lead to genes being either 'downregulated' or 'upregulated' in terms of their actual expression, even though the genes themselves have not been changed.

This new research involved pooling the results of many previous studies linking maternal obesity with DNA methylation of cells from the placenta - and came up with 27 different 'sites' on the genome where maternal obesity appears to have this kind of influence.

Re 'methylation' - key nutrients that are very important as 'methyl donors' include

  • Vitamin B9 or folate (also known as folic acid - the synthetic form found in supplements)
  • Vitamin B12
  • Choline, and a related nutrient
  • Betaine
And it is notable that in another newly-published study, balanced supplementation of all of these nutrients before conception and throughout pregnancy was shown to reduce the brain damage caused to the developing foetus by maternal alcohol consumption. See:

Of these nutrients, only folic acid is currently recommended for pregnancy - and yet risks for Vitamin B12 deficiency are increasing with the popularity of vegan or vegetarian diets without sufficient supplementation.

And dietary intakes of choline are suboptimal in the vast majority of women before and during pregnancy. Furthermore, choline deficiencies are firmly linked with both
  • fatty liver disease (associated with obesity, and excess intakes of sugar - especially fructose - as well as alcohol) and
  • compromised brain development in the offspring born to choline-deficient mothers.

For details of this research on the effects of maternal obesity, see:


See also:

03/03/2023 - Medical Xpress

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Most people think that as the fetus grows in the womb, the mother will be the most important factor influencing the child's future health, and this factor will undoubtedly prevail over all other possible ones. This belief is widely held in society and much research focuses on the characteristics and behaviors of the mother throughout her pregnancy.
 
Such is the case in the work published recently in Communications Biology which has studied

"the impact of the mother's body mass index at the beginning of pregnancy on the molecular profiles of the placenta, and more specifically on placental DNA methylation (addition of a group comprising one carbon and three hydrogens in a specific position in the DNA molecule),"

said Nora Fernández-Jiménez, lecturer at the Faculty of Medicine and Nursing.
 
"This is the largest study on placental DNA methylation conducted so far, involving a total of 2,631 mother-child pairs from Europe, North America and Australia," she added.
 
In contrast to the more familiar mutations –the substitution of one nucleotide for another in the DNA sequence–, methylation is a modification of DNA that regulates gene expression without altering the sequence.
 
"Recent studies indicate that methylation is the bridge between the intrauterine environment and the fetal genome.

"For example, the level of methylation of a region of the genome may increase as a result of the environment. Such an increase generally leads to the DNA becoming more compact, and as a result, the transcription machinery cannot access these regions and some genes are silenced.

"The opposite could also occur, in other words, the level of methylation in certain regions of the genome decreases in response to the environment. In this case, the DNA obtains an open configuration to which the transcription machinery has better accessibility, and gene expression would be increased as a result.

"In both cases, the sequence remains intact but the genome behaves in one way or another,"
explained the UPV/EHU researcher.
 
"In this work we have identified 27 sites in which variations in DNA methylation are observed and which seem specific to the placenta," pointed out Fernández-Jiménez.

It is worth remembering that the placenta is a fundamental organ in fetal growth and development, because it is the organ that connects the mother with the fetus and the organ through which the fetus is fed.
 
"Many of these identified sites are located near obesity-related genes and are enriched in metabolic pathways for cancer and oxidative stress.

"That doesn't mean that babies born to mothers with obesity problems will go on to develop cancer, but it is true that the placenta behaves like a tumor, it grows very quickly, and that leads us to think that there is an impact on the functioning of the placenta and fetal growth."
 
All these results suggest that placental DNA methylation may be one of the mechanisms by which maternal obesity is associated with adverse metabolic health outcomes in childhood, although Fernández-Jiménez stressed that further studies would be needed to corroborate these findings.
 
She went on to highlight the fact that "however legitimate our research may be, it should not be used to justify the mantra of mother-blaming, as it is very difficult to quantify the influence of mothers and their characteristics and behaviors versus other factors –mothers' parents or partners, families, society itself and the environment—surrounding the fetus and the newborn because they have never been so thoroughly researched."