Prenatal damage from dioxin shown to involve microRNAs

The research team, which included Narendra Singh, Mitzi Nagarkatti and Prakash Nagarkatti of the USC School of Medicine, demonstrated that exposure to dioxin (TCDD) during pregnancy in an experimental mouse model can cause significant toxicity to the fetus, and specifically to the organs that produce the immune cells that fight infections. They found that dioxin alters small molecules called microRNAs, which can affect the expression of a large number of genes.

The study examined over 608 microRNAs, and 78 of these were significantly altered following exposure to dioxin. On the basis of the pattern of changes in these molecules, the team was also able to predict that dioxin can alter several genes that regulate cancer. Many other physiological systems were also affected, including those involved in reproductive, gastrointestinal, hematological, inflammation, renal and urological diseases as well as genetic, endocrine and developmental disorders.

Dioxin is a highly toxic chemical produced as a byproduct of industrial processes, such as the manufacture of herbicides or pesticides or the bleaching of paper. Because it degrades slowly in the environment and is soluble in fats, dioxin can bio-accumulate in the food chain and is often found in high concentrations in the milk and fat of animals in contaminated regions.

"Our results lend more credence to the hypothesis that fetal exposure to environmental contaminants can have life-long effects," said Mitzi Nagarkatti. "Prenatal damage to the expression of microRNAs in the immune system could well impact the adult immune response."

The research was supported in part by the National Institutes of Health (R01ES09098, P01AT003961, R01AT006888, R01ES019313, R01MH094755) and the Veterans Administration (VA Merit Award 1I01BX001357).