By Roberta Attanasio
A few decades ago, the hypothesis of the Developmental Origins of Health and Disease (DOHaD), also called “Barker’s hypothesis,” stimulated interest in the fetal origins of adult disorders—as soon as it was formulated. Subsequent research by Mohan Manikkam and Michael Skinner helped establish the principle of transgenerational toxicity by showing that the effects of toxic chemicals can extend even to the third generation of offspring.
Indeed, it is now clear that early life development is a critical and unique window of vulnerability during which environmental exposures influence cellular programming in ways that shape health and disease later in life. While most research on the transgenerational effects of environmental chemicals focuses on the reproductive, nervous, or endocrine systems, results from a recently published study show that environmental toxins may also impair the immune system. Paige Lawrence, senior author of the study, said in a press release: “The old adage ‘you are what you eat’ is a touchstone for many aspects of human health. But in terms of the body’s ability to fights off infections, this study suggests that, to a certain extent, you may also be what your great-grandmother ate.”
To carry out the study, researchers exposed pregnant mice to dioxin, a common by-product of industrial production and waste incineration which is also found in some consumer products. Thus, dioxins are environmental pollutants. They belong to the so-called “dirty dozen”—a group of dangerous chemicals known as persistent organic pollutants (POPs). Dioxins are of concern because of their highly toxic potential. In the environment, dioxins tend to accumulate in the food chain. The higher an animal is in the food chain, the higher the concentration of dioxins. Therefore, dioxins are found in greater concentrations in animal-based food products. Once dioxins enter the body, they last a long time because of their chemical stability and their ability to be absorbed by fat tissue, where they are then stored. Their half-life in the body is estimated to be 7 to 11 years.
After exposing pregnant mothers to dioxin, they assessed the production and function of cytotoxic T cells in the offspring. Cytotoxic T cells are major players in the immune response—they kill not only cells infected by viruses, but also cancer cells. To do so, they infected the mice with influenza A virus, and found that exposure of the pregnant mothers to dioxin resulted in an impaired cytotoxic T cell response of the offspring against the influenza A virus. The impaired cytotoxic T cell response was observed not only in the offspring of the mice whose mothers where exposed to dioxin, but also in subsequent generations, up to the rodent equivalent of great-grandchildren.
Lawrence said: “When you are infected or receive a flu vaccine, the immune system ramps up production of specific kinds of white blood cells in response. The larger the response, the larger the army of white blood cells, enhancing the ability of the body to successfully fight off an infection. Having a smaller size army—which we see across multiple generations of mice in this study—means that you’re at risk for not fighting the infection as effectively.”