Most recently, researchers from Washington State University, led by biology professor Michael Skinner, reported last month that short-term exposure of pregnant rats to several kinds of chemicals caused ovarian disease not just in their daughters but also in two subsequent generations of females. Symptoms that paralleled those found in human polycystic ovarian disease and primary ovarian insufficiency, both of which can reduce fertility, were identified in the descendents of rats exposed to a fungicide, pesticides, dioxin, jet fuel, and a mixture of plastics, but not among descendents of controls.
When reproductive tract cells from the rats were examined, the disorders were linked to clusters of a carbon atom and three hydrogen atoms—called a methyl group—squatting above certain genes. Depending upon location and other factors, these methyl groups act to inhibit or ramp up gene expression. This altered "DNA methylation" pattern, triggered by exposure to the chemicals, is one of the known mechanisms through which the epigenome can control which genes are turned on and off, and therefore which proteins are produced within the cell. In this case, the new epigenetic structures were inherited intact from one generation to the next, even though only the original pregnant rats were exposed to the toxins.
2005, Dr. Skinner and colleagues—acknowledged pioneers in this new field of transgenerational epigenetics—reported in Science that four generations of offspring of a pregnant, fungicide-exposed rat exhibited reduced sperm counts and impaired sperm motility. Since then, Dr. Skinner's team has published a series of papers in leading journals documenting a range of conditions that can be induced in rats through an ancestral toxic exposure that does not change the genetic code; these include prostate disease, kidney disease, immune system abnormalities, and high cholesterol.
Rachel Morello-Frosch, an epidemiologist and environmental health professor at the University of California-Berkeley, said these new findings of transgenerational effects push the boundaries of current understanding of the long-term consequences of environmental contamination. "We're still just scratching the surface about the developmental effects of in utero exposures," Morello-Frosch said. "But this emerging science raises the stakes, with these recent studies suggesting that looking at the immediate offspring may be only looking at the tip of the iceberg."
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