It is well known that smoking during pregnancy can have serious effects on the baby’s health, but how exactly tobacco smoke exerts this toxic effect is not well understood. Mariona Bustamante and her colleagues at the Pregnancy and Childhood Epigenetics (PACE) Consortium hypothesised that maternal smoking could affect gene expression in the placenta by inducing chemical modifications (also called epigenetic changes) in its DNA. For example, adding methyl groups to certain DNA sites can alter the expression of nearby genes. “On the one hand, we know that the placenta plays a key role in ensuring a successful pregnancy; on the other hand, we know that certain environmental factors can alter DNA methylation patterns, which in turn affect the expression of certain genes,” explains Bustamante, who has been studying the impact of early-life environmental exposures on children’s health for several years.

DNA methylation, gene expression and poor birth outcomes

The research team put together seven independent cohort studies of the PACE consortium, involving a total of 1,700 mother-infant pairs from Australia, France, Spain, Canada and the United States. Their analysis revealed over 200 methylation sites that were associated with both maternal smoking and pre-term birth or lower weight at birth. These methylation sites were in or near genes involved in multiple placental functions, including regulation of inflammatory or growth signals. They also saw that this response to tobacco smoke was unique to the placenta—such DNA methylation changes were not observed in cord blood DNA.

“The genes and pathways identified in this study can help us decipher the mechanisms by which tobacco smoke affects placental function and foetal growth,” says Bustamante.