November 22, 2011
Smoking During Pregnancy Significantly Affects DNA Methylation, Gene Expression
Smoking during pregnancy profoundly changes both DNA and the expression of placental genes, a possible factor in physical changes that can last a lifetime, said researchers from Baylor College of Medicine in a report in the current edition of the journal Epigenetics.
In a study that correlated changes in DNA methylation (a chemical change that affects the level of gene expression) to changes in gene expression across the genome of the placenta (the small ovoid organ that nourishes the embryo in the uterus), Dr. Kjersti Aagaard and her colleagues found changes in methylation and gene expression of only 25 genes in non-smokers but 438 genes among smokers.Cellular pathways
Most of the changes in smokers affected cellular pathways associated with oxidative stress — the burden of toxic elements called free radicals that are produced in the course of normal metabolism.
Aagaard and her colleagues recently demonstrated that placentas from women who smoke demonstrate evidence of significant cellular damage from oxidative stress, and the new data describe the genetic mechanisms which result in those changes. (Methylation is a chemical change to DNA that can affect the ways genes are expressed and regulated.)
Many pregnant women continue smoking
The issue is troubling because as many as 20 percent of U.S. women continue to smoke during pregnancy. In 1964, the U.S. Surgeon General, in a landmark report on the effects of smoking on health, warned that the infants of women who smoked were more likely to be born low birth weight. Aagaard and members of her laboratory have been working to determine the reasons behind this for several years. Many of the toxins in cigarette smoke (namely polycyclic aromatic hydrocarbons) are the same as those found in polluted air.
In the study, Aagaard and her colleagues studied and compared placentas from 18 smokers and 18 non-smokers.
"Just as we expected from our previous studies in one gene, this dysregulation between DNA methylation and gene expression when a mom smokes is pretty profound," said Aagaard, an assistant professor of obstetrics and gynecology at BCM and senior author of the report. Even when she and her colleagues took into account other factors (like the gender of the baby,) the effect of smoking on the entire spectrum of methylation on genes in the placenta was significant.
This kind of altered methylation or chemical add-on in as few as six sites in the landscape of methylated genes and DNA can be associated with growth restriction in the developing embryo — a known effect of smoking.
The findings involved developing sophisticated data processing and analysis along with special statistical methodology that allowed Aagaard and her colleagues to take into account factors such as a known differential in weight between girl and boy babies.
Others who took part in the study included Melissa Suter, Jun Ma, Alan Harris, Lauren Patterson, Kathleen A. Brown, Cynthia Shope, Lori Showalter, Adi Abramovici, all of BCM.
Funding for this work came from the National Institutes of Health Director's New Innovator Pioneer Award to Aagaard and the Houston Research Education and Career Horizon Institutional Research and Academic Career Development Award to Suter.
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