Prenatal Exposure To Famine, Epigenetic Changes and Adult Health

06 December 2008 Filed under Cancer, Diet, Epigenetics, Heart health, Insulin-like Growth Factor Posted by jds » Comments Off

Prenatal exposure to famine can lead to changes in the embryo’s genes that may affect the adult person’s health into midlife, according to researchers at Columbia University Mailman School of Public Health and the Leiden University Medical Center in the Netherlands. Their findings show a trickle-down effect from pregnant women to the DNA of their unborn children and the timeframe over which such early damage can operate.

Previous studies have suggested that adult disease risk may be associated with unsuitable or adverse environmental conditions early in development. The data for this study are first to show that early-life environmental conditions can cause what are called epigenetic (epi= “on” + genetic) changes in humans that persist throughout life.

In Holland in 1944-45 during World War II a food embargo led to famine. Research indicates that children conceived during the Dutch Hunger Winter experienced detrimental health effects six decades later. Pre-natal exposure to the famine has been associated with cardiovascular disease and diabetes in later life.

Separate, related studies suggest possible associations of specific pre-natal nutritional imbalances and even of maternal over-nutrition with other health conditions including cancer.

The authors of the new study of the Dutch Hunger found that children exposed to the famine during the first 10 weeks after conception had less DNA methylation of the imprinted IGF2 gene than their unexposed same-sex siblings. By contrast, children exposed to the famine at the end of pregnancy showed no difference in methylation compared to their unexposed siblings.

Earlier research has found that in mice, IGF2 (insulin-like growth factor) regulates key processes in the placenta, providing “a mechanism for the role of imprinted genes in controlling placental nutrient supply and fetal growth.”

The new findings support the conclusion that very early development is 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 L.H. Lumey, MD, MPH, PhD, 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.”

This Dutch study has found overall that adults affected prenatally by the famine grew up to become more liable to cardiovascular disease, diabetes and possibly also schizophrenia (perhaps as a result of chemical changes in the mother due to stress). Ezra Susser, MD, DrPH, co-author, and 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 findings also show that birth weight is not a good marker for individuals with changes in methylation. Epigenetic differences were found among individuals who were exposed to famine early in gestation who have normal birth weights. For comparison purposes, the researchers also studied individuals who were exposed late in gestation and who therefore had lower birth weights. They did not see methylation changes in this group however. The study used sibling controls to avoid many potential study biases.

“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. As the next step, the Leiden group led by Drs. Heijmans and Slagboom will examine with Dr. Lumey the effect of famine on other human genes. They are also interested in the effect of other specific exposures during early development, including folic acid supplementation around conception as these may have an effect on methylation in the developing fetus.

“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.

The full study findings are published online in the Proceedings of the National Academy of Science November 4, 2008.

Edited by J. Strax from news released 10/30/2008 by Columbia University’s Mailman School of Public Health and University of Leiden article “Traces of Dutch ‘Hunger Winter’ in genetic material”.