“We cannot know from these studies if people are similarly at increased risk for these same diseases,” Wolstenholme said.
Still, the researchers wrote that their findings “have implications for the human populations that are exposed to dioxin and are experiencing declines in fertility and increases in adult onset disease, with a potential to transmit them to later generations.”
Dioxin builds up in the body and has up to a decade-long half-life in humans, so scientists say a woman who becomes pregnant even 20 years after exposure is at risk of transmitting the consequences of her exposure to later generations.
Most human studies of dioxins have focused on the direct exposure in adults and fetuses. A study of a 1976 industrial accident in Anshu Seveso, Italy, documented health defects in the grandchildren of women that conceived as long as 25 years after exposure to dioxin. No human studies have investigated how a person’s dioxin exposure will affect their great grandkids.
“Although transgenerational studies in humans are challenging, it will be very interesting for future epidemiologic research to investigate some of these populations, such as Vietnam veterans or the Seveso cohort, to evaluate whether similar increases incidence of kidney and ovarian disease are found,” said Carrie Breton, an environmental epidemiologist at the University of Southern California.
Earlier this year, Skinner’s research group found that pregnant rats exposed to high doses of dioxin and other chemicals passed down the negative health effects to their great-granddaughters, who developed cysts and other ovarian problems during puberty, even though they were not directly exposed.
In 2011, researchers found a decline in fertility in the third generation following dioxin exposure to pregnant mice.
In the new study, the rats were allowed to live longer so researchers could examine a wide variety of diseases and study how a legacy of dioxin exposure is recorded in sperm over generations.
“These findings are an example of environmentally induced epigenetic transgenerational inheritance of adult-onset disease,” the researchers wrote.
Previous studies with dioxin used high doses. The new study used a small percentage of the lethal oral dose for TCDD to avoid any acutely toxic effects from the exposure. The dose used is not comparable to people’s exposure from the environment. Due to bioaccumulation of dioxins, however, the dose in some people can get very high, Skinner said.
The researchers wrote that the purpose of the dosage was “not to assess environmental risk of exposure to dioxin,” but rather to “to investigate if exposure to TCDD could promote epigenetic transgenerational inheritance of disease.” The data could now be used to assess the environmental risk of exposure to dioxin.
In the study, pregnant rats were exposed to dioxin when their fetuses were 8 and 14 days old. Damage to the testes, prostate, kidney and ovaries were measured in the children and great-grandchildren after they were a year old.
The first generation offspring had more prostate disease and two types of ovarian disease, compared to control groups. Kidney disease, changes in puberty and ovarian disease were more prevalent in the great-grandkids than the control rats.
“Some of this damage persists into future generations, even without further dioxin exposure,” Wolstenholme said.
Abnormalities in puberty were nearly eight times higher in the third generation of female rats exposed to dioxin, compared to a control group. Forty-seven percent of third generation females had early puberty. Six percent in the control group had puberty abnormalities, with the majority being early onset.