Maternal glyphosate exposure causes autism-like behaviors in offspring through increased expression of soluble epoxide hydrolase

• DOI: 10.1073/pnas.1922287117
• Publication Date: 2020-05-12T20:55:24Z
• Authors: Yaoyu Pu; Jun Yang; Lijia Chang; Youge Qu; Siming Wang; Kai Zhang; Zhongwei Xiong; Jiancheng Zhang; Yunfei Tan; Xingming Wang; Yuko Fujita; Tamaki Ishima; Debin Wan; Sung Hee Hwang; Bruce D. Hammock; Kenji Hashimoto
• Keywords: Male; 570; Glyphosate; Intellectual and Developmental Disabilities (IDD); Autism; Biological Psychology; Glycine; 610; soluble epoxide hydrolase; Basic Behavioral and Social Science; Mice; 03 medical and health sciences; glyphosate; Pregnancy; Behavioral and Social Science; Psychology; 2.1 Biological and endogenous factors; 2.2 Factors relating to the physical environment; Animals; Autistic Disorder; Pediatric; Brain Chemistry; Epoxide Hydrolases; Behavior; 0303 health sciences; Biomedical and Clinical Sciences; gut microbiota; Behavior, Animal; Animal; Brain Disorders; Gastrointestinal Microbiome; 3. Good health; Disease Models, Animal; Mental Health; Maternal Exposure; Prenatal Exposure Delayed Effects; Disease Models; Women's Health; Mental health; Female; Microbiome

Significance Maternal exposure to high levels of the herbicide glyphosate may increase the risk for autism spectrum disorder (ASD) in offspring; however, the underlying mechanisms remain largely unknown. Maternal glyphosate exposure during pregnancy and lactation caused ASD-like behavioral abnormalities and abnormal composition of gut microbiota in murine male offspring. Soluble epoxide hydrolase (sEH) in the brain of offspring after maternal glyphosate exposure was higher than controls. Treatment with an sEH inhibitor from pregnancy to weaning prevented the onset of ASD-like behavioral abnormalities in offspring after maternal glyphosate exposure. The glyphosate exposures used here exceed any reasonable dietary, environmental, or occupational exposure, but they indicate that increased sEH plays a role in ASD-like behaviors in offspring.