Dioxin exposure in the womb, extra weight add up to health problems.

La Merrill M, BS Kuruvilla, D Pomp, LS Birnbaum and DW Threadgill. 2009. Dietary fat alters body composition, mammary development and P450 induction following maternal TCDD exposure in DBA/2J mice with low responsive aryl hydrocarbon receptors. Environmental Health Perspectives doi:10.1289/ehp.0800530.

Overweight mice whose mothers were exposed to dioxin during pregnancy die earlier, tend to have higher blood sugar levels and develop breasts sooner during puberty than those not exposed in the womb. Lean mice under the same circumstances had few of these effects.

The results are important because dioxin acts in a similar way in people as it does in these particular mice. The heavily studied mouse strain – called DBA – is considered dioxin-resistant because it responds very little to dioxin and not at all to less potent polyaromatic hydrocarbons. This means the mice show few of the health effects normally associated with exposure to dioxin.

The study supports previous published results that show dioxin exposure in lean DBA mice causes minimal health effects. The reason, say the authors, is that the lean DBA mice have less-active dioxin receptors than the overweight DBA mice. Because of this, the response to dioxin exposure in the lean mice is minimal, as other studies have shown.

But, the researchers take the study a step further by identifying unhealthy responses in the overweight mice that were also exposed to the pollutant before birth. The effects were not seen in the unexposed yet heavy mice.

Overweight people – like the heavy mice – also may be at risk for similar harmful effects because of the dioxins in the environment. The combination of exposure and excess weight may lead to chronic and deadly health problems such as diabetes and heart disease.

More than half of the US population is currently overweight. Diet, activity levels and the environment all contribute to a person's weight. In general, obesity increases risk of diabetes, cancer and cardiovascular disease.

Children, especially, are overweight and obese like never before. Obesity contributes to earlier puberty in girls. And type 2 diabetes, once unheard of in children, is now common.

Most people believe children are becoming diabetic because they are heavy. In adults, dioxin exposure is linked to diabetes. This study suggests that both being overweight and being exposed to dioxin may be leading to increased diabetes rates in children.

Generally, the new findings suggest people – if exposed before birth – may be more sensitive than previously thought to the harmful effects of the pollutant. Dioxin exposure during pregnancy reduced litter size and delayed one measure of puberty (breast duct development), regardless of diet, in the mice offspring.

The study challenges the long-standing belief that because of similarities to these DBA mice, people are at little risk of toxic effects associated with the contaminants. Due to these types of beliefs, current US government safety standards do not take into account the unique sensitivities that overweight people may have to these kinds of exposures.

The authors used a complex experimental design to examine how two mouse strains – one that is most resistant and one that is sensitive to the dioxin family of compounds – would respond if they were exposed to a low dose of dioxin during development and then were allowed to become overweight by eating a high fat diet (almost half of the calories came from fat, especially saturated fat). The diet used was similar to the content of a human diet rich in fatty, animal-based foods.

For animal studies, the doses used are considered low. They are about 100 to 1,000 times higher than the real-life exposures related to an industrial accident in Seveso, Italy, decades ago.

Dioxins are a family of long-lived compounds that can accumulate in the fat of animals and people. The compounds are formed during incomplete burning and are released in cigarette smoke, industrial waste and natural processes such as volcanos.

Dioxin and other industrial byproducts are difficult to regulate because the US government typically has less regulatory influence on waste products compared to commercial products.

Like many other fat-loving chemicals, dioxins contaminate the food supply. Virtually every human tissue, blood and urine sample measured has some level of dioxin.

Lean DBA mice born from mothers exposed to dioxin during pregnancy had no change in their blood glucose compared to the unexposed offpsring. The exposed mice, though, did have earlier signs of breast development than those not exposed.

The overweight DBA mice were another story. Those born to exposed mothers were very susceptible to dioxin. They had increased blood glucose levels and significant disruption of all measures of breast development, compared to overweight DBA mice that were not exposed to dioxin. Elevated blood sugars can lead to diabetes.

In humans, rats, and now mice, dioxin exposure is linked to delayed breast development at puberty.