Vulnerability of the placenta to air pollution: how does this affect the development of the unborn child?

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How does air pollution during pregnancy affect its course and the development of the unborn child? The research team from Inserm and the University of Grenoble Alpes were interested in how the DNA of the placenta would be altered by exposure to three major air pollutants. By comparing data from nearly 1,500 pregnant women, she was able to observe that exposure to these pollutants during pregnancy was associated with epigenetic modifications.[1] may alter fetal development, especially at the metabolic, immune and neurological levels. Its results will be published in Lancet Planetary Health, also show that periods of susceptibility to air pollutants will differ depending on the sex of the fetus, which affects the development of girls and boys differently.

Exposure to outdoor air pollution poses a serious risk to pregnancy success. In particular, it is assumed that it is the cause of cardiometabolic, respiratory or even neuropsychological pathologies in the unborn child. However, although its physiological effects have been studied, the molecular mechanisms are still poorly understood.

The placenta is an organ that plays a key role in the development of the fetus. Particularly vulnerable to numerous chemical compounds, it can be compared to an “archive” of the baby’s intrauterine environment: epigenetic modifications occurring in its cells partly reflect the mother’s environmental exposure during pregnancy. To study these modifications, we most often measure the level of DNA methylation, one of the best known epigenetic mechanisms involved in the control and expression of genes.

The research team, led by Johanna Lepel, an Inserm researcher from the Institute for the Development of Biosciences (Inserm/CNRS/University of Grenoble-Alpes), was interested in the effects of three air pollutants – carbon dioxide and nitrogen (NO).₂) and fine particles (PM_2.5 and prime minister₁₀) – on placental DNA methylation. Using data from three mother-child cohorts.[2] French, she was able to compare exposure to these pollutants and methylation levels of more than 1,500 participants during their pregnancies.

His results show significant effects of exposure to three air pollutants on placental DNA methylation levels related to genes involved in fetal development. A third of these changes were directly related to child development indicators (birth weight and height, head circumference, gestational age, etc.).

Other changes in the placenta affected genes involved in the development of the nervous system, immune system and metabolism, including genes involved in neonatal diabetes or obesity.

If these methylation changes are present in both sexes, the scientists were also able to identify modifications that have additional effects and affect different genes depending on the sex of the unborn child. This work identifies two distinct periods of pregnancy that are particularly vulnerable to epigenetic modifications by pollutants: early pregnancy (1^uh trimester) in boys and end of pregnancy (3^e trimester) in girls.

“Our results show that exposure to air pollution during pregnancy causes changes in placental DNA methylation that are specific to each of the two sexes. points out Johanna Lepel. AGAINSTand different exposures may contribute to different changes in the development and course of pregnancy depending on the sex of the unborn child. »

Thus, boys showed significant changes in methylation at the level of genes that are critical for the development of the nervous system and intelligence.

“These observations support a growing body of research linking exposure to air pollution during pregnancy with impaired neurodevelopment and/or cognitive decline with greater vulnerability in male children.” explains Lucille Broseus, Inserm researcher and first author of the publication.

In girls, methylation affected genes involved in fetal development and the regulation of oxidative stress. Thus, they may be associated with developmental defects that may increase the risk of developing chronic metabolic diseases (hypertension, diabetes, obesity, etc.) later in life, as well as the occurrence of miscarriages or preeclampsia in the mother.[3].

In summary, this work provides new evidence on the epigenetic mechanisms involved in the deregulation of fetal growth by air pollution and which may be responsible for long-term metabolic changes.

” Future studies may examine whether epigenetic changes in the placenta caused by exposure to air pollution during pregnancy persist after birth and how they may affect development during childhood.adds Johanna Lepel. In addition, since this research work was conducted in French cohorts, the results will need to be tested in populations from other geographic regions and with different genetic profiles. “, concludes the researcher.

[1] Epigenetic modifications are materialized by biochemical marks present on DNA. Reversible, they do not cause modification of the DNA sequence, but nevertheless cause changes in gene expression. They are induced by the environment in a broad sense: the cell receives signals informing it about its environment and specializes or adjusts its activities accordingly.

[2]The EDEN cohorts led by Inserm, the University Hospital of Poitiers and the University Hospital of Nancy; PELAGIA led by Inserm; and SEPAGES, led by Inserme and the Grenoble Alpes PE.

[3]Preeclampsia is a pregnancy pathology characterized by increased blood pressure and the amount of protein in the urine. This can happen in the middle of the second trimester or later, shortly before birth, and sometimes even after it. Responsible for a third of very preterm births in France, this syndrome is the leading cause of intrauterine growth restriction. Without treatment, it can lead to the death of the mother and/or baby.