Placental vulnerability to air pollution: what effects on the development of the unborn child?

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(© Image: Depositphotos)
(© Image: Depositphotos)
How does exposure to air pollution during pregnancy affect the pregnancy and the development of the unborn child? A research team from Inserm and Grenoble Alpes University has investigated how placental DNA is modified by exposure to three major air pollutants. By comparing data obtained from almost 1,500 pregnant women, they were able to observe that exposure to these pollutants during pregnancy was associated with epigenetic modifications [1] likely to alter fetal development, particularly at the metabolic, immune and neurological levels. Her findings, to be published in The Lancet Planetary Health , also show that periods of susceptibility to air pollutants differ according to the sex of the fetus, impacting development in a differentiated way between girls and boys.

Exposure to outdoor air pollution poses a major risk to a healthy pregnancy. In particular, it is suspected of causing cardiometabolic, respiratory and neuropsychological pathologies in the unborn child. However, while its physiological effects have been studied, the molecular mechanisms involved are still poorly understood.

The placenta plays a key role in fetal development. Particularly vulnerable to many chemical compounds, it can be likened to an "archive" testifying to the child’s prenatal environment: epigenetic modifications occurring in its cells partly reflect the mother’s environmental exposures during pregnancy. To study these modifications, we most often measure the level of DNA methylation, one of the best-known epigenetic mechanisms involved in gene control and expression.

A research team led by Inserm researcher Johanna Lepeule at the Institut pour l’avancée des biosciences (Inserm/CNRS/Université Grenoble Alpes) has been looking at the impact of three air pollutants - nitrogen dioxide (NO2), and fine particles (PMimpact of three air pollutants - nitrogen dioxide (NO2), and fine particles (PM2.5 and PM10) - on placental DNA methylation. Using data from three French mother-child cohorts [2], she was able to compare exposure to these pollutants and methylation levels in over 1,500 participants during pregnancy.

The results show a significant impact of exposure to the three air pollutants on placental DNA methylation levels concerning genes involved in fetal development. A third of these changes were directly associated with indicators of child development (birth weight and height, head circumference, length of pregnancy, etc.).

Other placental modifications concerned genes involved in the development of the nervous system, the immune system and metabolism - including genes implicated in the onset of neonatal diabetes or obesity.

While these alterations in methylation are present in both sexes, the scientists were also able to identify modifications with an additional impact, affecting different genes depending on the sex of the unborn child. Two different gestation periods particularly vulnerable to epigenetic modifications under the effect of pollutants emerge from this work: the beginning of pregnancy (1st trimester) in boys and the end of pregnancy (3rd trimester) in girls.

Our results show that exposure to air pollution during pregnancy induces gender-specific changes in placental DNA methylation," says Johanna Lepeule.This differentiated impact could contribute to alterations in the development and course of pregnancy that differ according to the sex of the unborn child."

In boys, significant methylation alterations were detected in genes critically involved in the development of the nervous system and intellect.

"These observations support the growing number of studies associating exposure to air pollution during pregnancy with impaired neurodevelopment and/or reduced cognitive capacity, with a greater vulnerability of male children," explains Lucile Broséus, Inserm researcher and first author of the publication.

In girls, the methylations affected genes involved in fetal development and the regulation of oxidative stress. They could thus be associated with developmental defects likely to increase the risk of developing chronic metabolic diseases (hypertension, diabetes, obesity...) later in life, but also with the occurrence of miscarriage or pre-eclampsia in the mother [3] .

This work therefore provides new data concerning the epigenetic mechanisms involved in the deregulation of fetal growth under the effect of air pollution, and which could be at the origin of long-term changes in metabolism.

Future studies could investigate whether placental epigenetic changes caused by exposure to air pollution during pregnancy persist after delivery, and how they might influence development during childhood," adds Johanna Lepeule. Furthermore, as this research was carried out on French cohorts, its results will need to be verified in populations from other geographical regions and with different genetic profiles ", concludes the researcher.

[1] Epigenetic modifications are biochemical marks on DNA. Reversible, they do not modify the DNA sequence, but do induce changes in gene expression. They are induced by the environment in the broadest sense: the cell receives signals informing it about its environment, and specializes accordingly, or adjusts its activity.

[2] The EDEN cohorts, led by Inserm, CHU Poitiers and CHU Nancy; PELAGIE, led by Inserm; and SEPAGES, led by Inserm and CHU Grenoble Alpes.

[3] Pre-eclampsia is a pathology of pregnancy characterized by elevated blood pressure and protein levels in the urine. It can occur in the middle of the second trimester or later, shortly before or even after delivery. Responsible for a third of very premature births in France, this syndrome is a major cause of intrauterine growth retardation. Untreated, it can lead to the death of mother and/or child.