Gestational and lactational exposure to glyphosate and a glyphosate-based herbicide causes sex-dependent effects on neurodevelopment and monoaminergic markers in rats

Glyphosate (Glyph) exposure during the gestational and lactational periods have been linked to neurodevelopmental alterations in humans and animal models, and it has been proposed to induce autistic-like traits in rodents. This study evaluated the effects of gestational and lactational exposure to Glyph and a glyphosate-based herbicide (GBH) on neurodevelopmental and monoaminergic outcomes in male and female rat offspring, using valproic acid (VPA) as a pharmacological model of autism. Pregnant dams were orally treated with 50mg Glyph/L in distilled water or with GBH throughout gestation and lactation. The VPA group received a single intraperitoneal injection of 500mg/kg on gestational day 12.5, while controls received only distilled water. Male and female pups underwent a battery of neurodevelopmental tests from postnatal day (PND) 3 to 21, and brains were collected at PND 21 to assess monoaminergic markers. Offspring exposed to VPA showed alterations in early social interactions. Female pups treated with Glyph or VPA mainly exhibited reduced body weight during lactation. Delayed performance in the negative geotaxis test was observed in female pups exposed to Glyph 9, and in VPA pups at PND 5 and 9. Only male GBH-exposed pups exhibited impairments in righting reflexes on PND 7. Neurochemical analyses revealed sex-dependent alterations in dopamine, serotonin, and their metabolites in the prefrontal cortex, striatum, nucleus accumbens, ventral midbrain, hippocampus, and amygdala. These findings show that gestational and lactational exposure to low levels of Glyph or GBH induces some sexually dimorphic effects on behavior and neurochemistry, resembling those seen in ASD-like models.