Perinatal exposure to glyphosate‐based herbicides induced neurodevelopmental behaviors impairments and increased oxidative stress in the prefrontal cortex and hippocampus in offspring

• Published in: International journal of developmental neuroscience 2022-10, Vol.82 (6), p.528-538
• Main Authors: Oliveira, Maria A. L., Rojas, Viviana C. T., Sá, Josiane C., Novais, Cíntia O., Silva, Mariana S., Almeida Paula, Hudsara Aparecida, Kirsten, Thiago B., Bernardi, Maria Martha, Pinheiro, Lucas Cézar, Giusti‐Paiva, Alexandre, Vilela, Fabiana C.
• Format: Article
• Language: English
• Subjects: Animals; Autism Spectrum Disorder; Female; glutathione; Glycine - analogs & derivatives; Glyphosate; herbicide; Herbicides - toxicity; Hippocampus; Humans; Organophosphates; Oxidative Stress; Prefrontal Cortex; Pregnancy; Prenatal Exposure Delayed Effects - chemically induced; Rats; Rats, Wistar
• ISSN: 0736-5748; 1873-474X
• DOI: 10.1002/jdn.10207

Glyphosate is the organophosphate pesticide most widely used in the world. Recent studies correlate exposure to glyphosate and the emergence of neurodevelopmental disorders. Therefore, it was objective to propose a rat model of perinatal exposure to glyphosate‐based herbicides (GBH) to study associated neurodevelopmental disorders. Behavioral aspects and brain pathways were assessed in the prepubertal phase. For this, maternal treatment occurred throughout the entire gestation period (from GD0) until weaning on postnatal day 22 (PND 22). Control group received oral gavage with 5 mL/kg of saline per day and GBH group received oral gavage with 50 mg/kg of GBH per day (n = 10 per group). Maternal behavior was evaluated in PND 2–6. Offspring were evaluated for quantification of ultrasonic vocalizations (PND 5); homing behavior test (PND 13); and hole board, social play behavior, open field, and object recognition tests (PND 28–32). Prefrontal cortex and hippocampus of the offspring were processed to evaluate oxidative stress. Maternal exposure to GBH impaired early social communication, olfactory discrimination, social play behavior, and the exploration of objects, in addition to increasing repetitive and stereotyped movements. GBH also increased oxidative stress. Therefore, perinatal GBH exposure induced behavioral and oxidative stress impairments in rats associated with neurodevelopmental disorders. The manifestations found in the offspring are in accordance with symptoms of autism spectrum disorder. Maternal exposure to GBH impaired early communication and olfactory discrimination, reduced social play behavior and increased repetitive and stereotyped movements. These changes were accompanied by increased oxidative stress in the brain of the offspring. Our data demonstrate that perinatal GBH exposure compromises neurobehaviour with symptoms like those found in neurodevelopmental disorders such as autism spectrum disorder.