A study of 668 mother-child pairs shows that maternal blood pressure during pregnancy is associated with the level of expression of placental genes involved in the development of the respiratory system of the unborn child. These results reinforce knowledge on the role of epigenetic mechanisms in the developmental origin of diseases.
Data on the influence of environmental factors on the early development of children are accumulating. Population studies suggest, for example, that the air pollution to which pregnant women may be exposed is associated with poorer respiratory health in their child after birth. These anomalies could be mediated in particular by an increase in maternal blood pressure and by dysfunctions of the placenta, a crucial organ in charge of nutritive, gaseous and hormonal exchanges between the mother and the child. The underlying mechanisms remain to be described more precisely in order to prevent the consequences.
At the Institute for the Advancement of Biosciences in Grenoble, the Environmental Epidemiology Applied to Development and Respiratory Health (EDES) team works precisely to identify avoidable environmental risk factors associated with impaired growth. , neurological development and respiratory health of children. Researchers Lucile Broséus and Johanna Lepeule have studied epigenetics, that is to say the chemical modifications of DNA that modulate gene expression. ” A growing body of work suggests that the epigenetic changes that occur in placental cells are a reflection of environmental exposures during pregnancy, the functioning of the placenta, and the course of pregnancy.explains Johanna Lepeule. To study these changes, we most often measure the level of methylation DNA, one of the best known epigenetic mechanisms. »
Maternal blood pressure and placental DNA methylation
After showing that the exposure of pregnant women to air pollution is associated with changes in the methylation of genes in the cells of the placenta – in particular at the level of genes known to promote hypoxia (lack of oxygen) or pre-eclampsia (hypertensive disease linked to placental dysfunction) – the researchers wanted to assess the placental epigenetic changes associated with the mother’s blood pressure.
This work was conducted with 668 mother-child couples included in the French EDEN cohort. During this study, the blood pressure of expectant mothers was frequently measured and recorded. In addition, a sample of placental tissue was taken at the time of their delivery and stored. This allowed the researchers to conduct two types of analysis: On the one hand, we have shown that maternal blood pressure is associated with methylation levels in 64 regions of the genome, among which a large number are known to be involved in child respiratory development. On the other hand, it appeared that this association is partly linked to changes in the cellular composition of the placenta. However, this composition had until then been little considered in this type of study. »
Respiratory health and neurodevelopment
These epigenetic marks could have a long-term effect. They could partly explain the associations between exposure to air pollution (or other environmental factors) during pregnancy and the respiratory or neurodevelopmental health of the child after birth. They consolidate the DOHaD theory (Developpemental Origins of Health and Disease)which suggests that health and the onset of disease throughout life rely on early mechanisms that occur as early as the period in utero. Also, the researchers now want to check whether it is possible to directly link their observations with the child’s respiratory health. ” We want to investigate the impact of these placental changes on neurodevelopmentdescribes Johanna Lepeule. For this, we will continue to work from data from the EDEN cohort, but also from those collected in two other French cohorts: PELAGIA et SEPAGES. By coupling these data, we should obtain more robust results. Once the links and mechanisms between early exposure and later health problems are described, it will be easier to prevent them. ” In the long term, why not imagine drugs that would be developed to correct these levels of methylation? asks the researcher.
Lucile Broséus and Johanna Lepeule are respectively post-doctoral researcher and researcher in the team Environmental epidemiology applied to development and respiratory healthat the Grenoble Institute for the Advancement of Biosciences (unit 1209 Inserm/CNRS/Grenoble Alpes University).
Source : L Broséus et coll. Maternal blood pressure associates with placental DNA methylation both directly and through alterations in cell-type composition. BMC Medicineedition of October 20, 2022. DOI: 10.1186/s12916-022–02610‑y