Researchers from Columbia University Mailman School of Public Health and the Leiden University Medical Center in the Netherlands say that their findings show trickle-down effect from pregnant women to the DNA of their unborn children, and the timeframe over which such early damage can operate.
Reporting their findings online in the Proceedings of the National Academy of Science, the researchers claim that theirs is the first study to show that early-life environmental conditions can cause epigenetic changes in humans that persist throughout life.
The researchers say that their study has revealed that children conceived during the Dutch Hunger Winter in 1944-45, caused by a food embargo on the Netherlands in World War II, experienced persistent detrimental health effects six decades later.
They say that the children who were exposed to the famine during the first 10 weeks after conception had less DNA methylation of the imprinted IGF2 gene, compared to their unexposed same-sex siblings.
According to them, children exposed to the famine at the end of pregnancy did not show any difference in methylation compared to their unexposed siblings.
The researchers said that the findings suggested very early development to be a crucial period in establishing and maintaining epigenetic marks.
Epigenetic changes, while not altering the DNA sequence, can alter which genes are expressed. Genes that might otherwise be activated could be silenced by epigenetic changes or vice versa, and this could impact an individual's risk for adverse health outcomes later in life.
"We believe that our study provides the first evidence that certain environmental conditions early in human development can result in persistent changes in epigenetic information," says Dr. L.H. Lumey, associate clinical professor of Epidemiology at the Mailman School of Public Health and senior author.
"If there are indeed relationships between adverse conditions during development and adult health, then these epigenetic changes might provide a mechanism to explain the link." Dr. Ezra Susser, co-author.
Anna Cheskis Gelman and Murray Charles Gelman Professor and chair of Epidemiology at the Mailman School, noted: "These findings are particularly intriguing in light of our reports on increased rates of schizophrenia after early gestational exposure to famine."
The results of the latest study also suggest that birth weight is not a good marker for individuals with changes in methylation.
"Our study illustrates that to monitor the crucial stages of early development, we can not rely on birth weight alone as an indicator of maternal nutrition. We must use our knowledge of the crucial events that took place during that period," observes Dr. Lumey.
The researchers are not planning to examine the effect of famine on other human genes. They will also study the effect of other specific exposures during early development, including folic acid supplementation around conception as they may have an effect on methylation in the developing foetus.
"Understanding how epigenetic control responds to well defined early exposures may shed light on the link between development and health over a life time and ultimately suggest new ways to prevent human disease," said Dr. Lumey.