Stopping smoking before pregnancy is known to significantly decrease health risks for both mother and child. The work of a team from Inserm, CNRS and Université Grenoble Alpes within the Institute for the Advancement of Biosciences, published in BMC Medicine go further, showing for the first time that tobacco consumption, even when stopped before pregnancy, can have consequences for the placenta. Through the study of the placental DNA of 568 women, researchers show that smoking during but also before pregnancy causes epigenetic changes (DNA methylation) which could have consequences on its course.
Although tobacco consumption during pregnancy has been shown to have numerous negative consequences for the health of mother and child, the mechanisms involved are still poorly understood. Previous studies have linked tobacco use during pregnancy to alterations in DNA methylation – a form of epigenetic modification (see box) involved in gene expression – in umbilical cord blood and cells. of the placenta. Indeed, the latter plays a crucial role in the development of the fetus, while remaining vulnerable to many chemical compounds.
In contrast, the impact of exposure to tobacco before pregnancy on methylation of placental DNA has so far never been studied.
A team from Inserm, CNRS and Université Grenoble Alpes, within the Institute for the Advancement of Biosciences, measured and compared the impact on pregnant women of tobacco consumption within 3 months. preceding pregnancy and / or during pregnancy on methylation of placental DNA.
Researchers studied DNA from placenta samples taken during childbirth from 568 women in the EDEN cohort  divided into three categories: non-smokers (who have not smoked for the three months preceding pregnancy or during pregnancy), former smokers (cessation of consumption in the three months preceding pregnancy) and smokers (consumption within three months preceding pregnancy and throughout pregnancy).
Scientists observed that, in smokers, 178 regions of the placental genome showed alterations in DNA methylation. In former smokers, the researchers identified 26 of these 178 regions whose DNA methylation was still impaired. Methylation of the other 152 regions was altered only in women who smoked during pregnancy.
The altered regions most often corresponded to so-called enhancers, which remotely control the activation or repression of genes. In addition, some of them were located on genes known to have an important role in the development of the fetus.
« While a large number of regions appear to have a normal methylation profile in women after smoking cessation, the presence of some DNA methylation changes in the placenta of women who quit smoking before pregnancy suggests the existence of an epigenetic memory of exposure to tobacco », Explains Inserm researcher Johanna Lepeule, who led this work. According to her, changes in the methylation of placental DNA in genes linked to the development of the fetus and regions enhancers may partly explain the effects of smoking observed on the fetus and subsequent health of the child.
The next steps in this work will aim to determine whether these alterations impact mechanisms involved in the development of the fetus and whether they can have consequences on the health of the child.
 Pregnant women were recruited between 2003 and 2006 in the university hospitals of Nancy and Poitiers.
Epigenetic modifications are materialized by biochemical marks present on the DNA. Reversible, they do not lead to any modification of the DNA sequence but nevertheless induce changes in gene expression. They are induced by the environment in the broad sense: the cell receives signals informing it about its environment, and specializes accordingly, or adjusts its activity. The best characterized epigenetic marks are DNA methylations, involved in the control of gene expression.