Maternal Smoking During Pregnancy Leaves Its Lasting Mark On The Child’s Genetic Make-up
5. April 2016
First study to show changes in epigenetic enhancer regions and their relation to the child’s diseases later in life
Photo: André Künzelmann, UFZ
If mothers smoke during pregnancy, they influence the epigenetic programming of their unborn child’s genetic make-up in the long term. This may give rise to an increased risk of the child developing lung diseases later in life. Researchers at the Helmholtz Centre for Environmental Research (UFZ) in Leipzig, the German Cancer Research Center (DKFZ) in Heidelberg and the Heidelberg University discovered that these changes are not limited to individual regions of DNA. Dr. Irina Lehmann, Environmental Immunologist at the UFZ, explains, that they were able to demonstrate for the first time that exposure to tobacco smoke also causes epigenetic changes in enhancers of gene expression.These deregulated enhancers are distributed throughout the child’s entire genome. The research results were published in the journal “Molecular Systems Biology”.
The underlying data comes from the epidemiological study entitled “Lifestyle and environmental factors and their Influence on Newborns Allergy risk” (LiNA). In this study, researchers asked which environmental factors could have a negative impact on children’s health during pregnancy. In collaboration with the Municipal Hospital St. Georg in Leipzig, UFZ researchers have been monitoring 622 mothers and their children since 2006. For their current work, two groups of mother-child pairs were examined: mothers who smoked during pregnancy and mothers who were not exposed to tobacco smoke.
Together with the genome researchers headed by Prof. Dr. Roland Eils, who is working at the DKFZ and the University of Heidelberg, the scientists examined the epigenome of the mothers and the children. They wanted to determine whether there was evidence of epigenetic changes in the smoking families. According to Dr. Lehmann they were able to find evidence of epigenetic changes in smoking mothers as well as in the umbilical cord blood of the newborn babies. The changes thus occur in the womb and affect the unborn child’s gene regulation.
The researchers determined that smoking particularly affects enhancer regions in the genome. Enhancers are DNA regions that regulate the expression of one or more genes. If an enhancer region is affected by the effects of smoking, this may lead to deregulation of several genes at the same time, stresses Dr. Lehmann. The researchers give an example of the consequences of a deregulated enhancer in their work: the enzyme JNK2 plays a role in inflammatory responses. If the enhancer that activates JNK2 is now affected, this may increase the risk of lung diseases in the children’s later life.
The researchers also determined that the epigenetic effects observed in the umbilical cord blood at birth can still be seen several years after the child is born. However, it could not be ascertained beyond doubt whether these effects are long-term impacts of exposure to smoke prior to birth. Dr. Lehmann points out that children who are exposed to tobacco smoke even before being born usually continue to be exposed to this after their birth. The prolonged exposure to cigarette smoke after birth may contribute to the observed stability of epigenetic changes.
In their analysis, the researchers identified more than 400 enhancers affected by tobacco smoke. They regulate genes that play a role in a variety of diseases such as diabetes, adiposity or even cancer. “This discovery will allow us to start understanding the mechanisms that make smoking the cause of such a wide range of diseases,” says Prof. Eils.