Bruce Hammock, Ph.D.
University of California, Davis
A new NIEHS-funded study revealed a possible mechanism by which exposure to the herbicide glyphosate during pregnancy may increase the risk for autism spectrum disorder (ASD) in offspring. According to the study, an enzyme called soluble epoxide hydrolase (sEH) plays a key role in the development of ASD-like behaviors after maternal glyphosate exposure. The sEH enzyme, which helps to break down polyunsaturated fatty acids, has been shown to be involved in other neurodevelopmental disorders related to inflammation.
The team exposed pregnant mice to high levels of glyphosate during pregnancy and lactation, then assessed ASD-like behaviors in their offspring. Juvenile mice who were exposed to glyphosate in the womb and during lactation displayed ASD-like cognitive and social interaction deficits, unlike the unexposed group. Exposed offspring also had altered microbiomes compared with the unexposed group.
To understand the underlying mechanism, the researchers compared expression of sEH in the brains of exposed and unexposed offspring. Protein levels and gene expression of sEH were significantly higher in the brains of the exposed mice. Treatment with an sEH inhibitor from pregnancy through weaning prevented ASD-like behaviors in exposed offspring. According to the authors, these findings suggest that sEH inhibitors may prove promising in preventing or treating ASD.
Citation: Pu Y, Yang J, Chang L, Qu Y, Wang S, Zhang K, Xiong Z, Zhang J, Tan Y, Wang X, Fujita Y, Ishima T, Wang D, Hwang SH, Hammock BD, Hashimoto K. 2020. Maternal glyphosate exposure causes autism-like behaviors in offspring through increased expression of soluble epoxide hydrolase. Proc Natl Acad Sci U S A 117(21):11753–11759.