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Stem Cell Initiative
PRENATAL HEALTH
| Sixty Years Later, Genome Retains Sign of Famine |
The marks may explain how famine during pregnancy could be linked to diseases like cardiovascular and neuropsychiatric disorders that develop decades later in adulthood, says one of the study’s senior authors, L.H. Lumey, MD, PhD, associate professor of clinical epidemiology.
The idea that many adult diseases have roots in the prenatal environment has become increasingly widespread in the last 10 to 15 years. Studies in animals have shown that health in adulthood can be influenced by marks acquired by the genome before birth, and that these marks are related to the mother’s nutrition.
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| An American bomber drops food over the Netherlands at the end of World War II. Famine endured by pregnant women during the German blockade of the Netherlands left permanent traces on their children's DNA. |
Dr. Lumey and his colleagues found that the genomes of 60-year-old men and women who were conceived during the famine had fewer marks on a gene called IGF2 than their unexposed siblings. Such “epigenetic” alterations do not mutate a gene’s DNA but can cause life-long changes in the activity of certain genes by adding or subtracting chemical compounds to the DNA strand.
It is the first time that environmental conditions during early development have been found to cause life-long epigenetic changes to the human genome.
Because IGF2 plays a major role in growth, the researchers speculate that the epigenetic changes may have altered the activity of IGF2, leading to an adult metabolism more suited for a time of starvation than for the time of abundance following the end of World War II. The epigenetic changes to IGF2 also may play a role in schizophrenia, which was first linked to prenatal famine exposure by Ezra Susser, MD, DrPH, professor of epidemiology and psychiatry and a co-author of the current study. “Epigenetic changes to IGF2 have been recently hypothesized to contribute to schizophrenia,” Dr. Susser says, “and these new findings provide another piece of evidence to bolster that hypothesis.”
Dr. Lumey and his colleagues are now examining the relationship between changes in IGF2 activity and adult health. “That’s the missing link. If we make that connection, then we’ll have a mechanism that links famine exposure to adult health,” Dr. Lumey says. “And ultimately that may suggest new ways to prevent human disease.”
PNAS 105(44): 17046 - 17049
The study was supported by the NIH, Netherlands Heart Foundation, Netherlands Organization for Scientific Research, and the European Union.
| The original Dutch Famine Study – pioneered in the 1960s by two Mailman researchers, Mervyn Susser and Zena Stein – is considered one of the classic investigations in the field of epidemiology. One of the study’s first findings inspired research that led to the recommendation that women take folate supplements to prevent neural tube defects in their children. A small group of researchers continue to study the descendants of the Dutch Hunger Winter and other famines. They gathered last month at the first international workshop on long-term consequences of famine, organized by Dr. Lumey, to identify future research priorities. For further information see http://www.lorentzcenter.nl |
