Abstract
Prenatal chemical exposure is a growing health concern as it can cause a lifelong lasting effect on the psychological and physiological health in both pregnant mother and offspring, which supports the Developmental Origins of Health and Disease (DOHaD) hypothesis. In recent years, many reports link prenatal exposure of environmental chemicals to reproductive health, epigenetic modification, and pathological diseases acting on the direct disruption of cells and structures of the nervous system and epigenetic changes. Glyphosate, the main compound of a broadly applied herbicide, is the negative substance on the Organization for Economic Cooperation and Development (OECD) Test Guidelines; however, the safeties of glyphosate or aminomethylphosphonic acid (AMPA), a metabolite in the soil, are unknown. The primary herbicidal function of glyphosate is to inhibit a key plant enzyme, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), which participates in the biosynthesis of aromatic amino acids (including phenylalanine, tyrosine, and tryptophan) via the shikimate pathway in bacteria, fungi, and plants. Glyphosate may have the potential to modify the animal and human gut microbiota. Previously we have shown that acute exposure of 100 or 250 mg/kg-glyphosate, or 250 mg/kg-AMPA to pregnant rats lead to neuronal and behavioral disorder in developing cerebellum. In this study, we investigated the effects of prenatal chronic glyphosate exposure on the cerebellar cortex in immature offspring. Pregnant rats were exposed to glyphosate-water (approximately 15.625 mg/kg/day; total dosage is 250 mg/kg) from gestational day 4 (G4) until G19. Prenatal chronic glyphosate exposure caused a decrease of Purkinje cells and an increase of microglia in developing cerebellum. Therefore, glyphosate may have some developmental neurotoxicity.
