Maternal glyphosate-based herbicide exposure alters antioxidant-related genes in the brain and serum metabolites of male rat offspring

• Published in: Neurotoxicology (Park Forest South) Vol. 74; pp. 121 - 131
• Main Authors: de Souza, Janaina Sena, Laureano-Melo, Roberto, Herai, Roberto Hirochi, da Conceição, Rodrigo Rodrigues, Oliveira, Kelen Carneiro, da Silva, Ismael Dale Cotrim Guerreiro, Dias-da-Silva, Magnus Régios, Romano, Renata Marino, Romano, Marco Aurélio, Maciel, Rui Monteiro de Barros, Chiamolera, Maria Izabel, Giannocco, Gisele
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-09-2019; Elsevier BV
• Subjects: Agricultural engineering; Agrochemicals; Alzheimer's disease; Animals; Antioxidant enzymes; Antioxidants; Antioxidants - metabolism; Autism; Brain; Brain Chemistry - drug effects; Brain Chemistry - genetics; Catalase; Cerebellum; Distilled water; Epidemiology; Exposure; Female; Gene expression; Gene Expression Regulation - drug effects; Gene Regulatory Networks - drug effects; Genes; Genetic engineering; Gestational Age; Glutathione; Glutathione peroxidase; Glycine - analogs & derivatives; Glycine - toxicity; Glyphosate; Glyphosate-based herbicide; Health risks; Herbicides; Herbicides - toxicity; Hypoxia; Inflammation; Inflammation - chemically induced; Inflammation - genetics; Inflammation - pathology; Inflammatory response; Lecithin; Lipid metabolism; Lipid Metabolism - drug effects; Lipid Metabolism - genetics; Lipids; Lysophosphatidylcholine; Male; Maternal Exposure - adverse effects; Metabolites; Metabolome - drug effects; Metabolomics; Neurodegenerative diseases; Neuroglobin; Neurological diseases; Offspring; Organic chemistry; Oxidative stress; Oxidative Stress - drug effects; Oxygen; Oxygen probes; Peroxidase; Phosphatidylcholine; Pregnancy; Prenatal Exposure Delayed Effects - genetics; Rats; Rats, Wistar; Glyphosate-based herbicide; Oxidative stress; Metabolomics; Inflammation; Gene expression; Antioxidant enzymes
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2019.06.004

•GBH changes inflammation related genes in the cortex and the cerebellum of offspring of exposed pregnant rat.•GBH changes oxidative stress related genes in the cortex and the cerebellum of offspring of exposed pregnant rat.•GBH affects serum metabolites in offspring of exposed pregnant rat.
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In response to the rapid development of genetically engineered glyphosate-tolerant crops, the use of glyphosate-based herbicides (GBHs), in agriculture, has increased substantially. Currently, it is estimated that 747 million kg of GBHs are applied per year. Although several epidemiological studies have demonstrated that there are health risks associated with GBH exposure, the effects these chemicals have on the oxidative and inflammatory response in the brain are still unclear. In fact, alterations in these processes could contribute to the development of neurological diseases, such as Alzheimer’s disease and autism spectrum disorders. The present study exposed pregnant rats to GBH and evaluated changes in the expression of genes related to oxidnte defense and inflammation response and monitored the serum metabolome in the adult male offspring. Pregnant Wistar rats were administered distilled water or Roundup®, at either 5 and 50 mg/kg/day, (p.o.) from gestational day (GD) 18 to postnatal day (PND) 5. There was a significant increase in the gene expression levels of Neuroglobin (Ngb – oxygen storage and tissue protection) (105%, p = 0.031), Glutathione Peroxidase 1 (Gpx1 – oxidative stress) (95%, p = 0.005), Prostaglandin-Endoperoxidase Synthase 1 (Ptgs1 - inflammation) (109%, p = 0.033) and Hypoxia inducible factor 1 subunit alpha (Hif1α – oxygen sensor) (73%, p = 0.017), in the cerebellum of PND90 rats perinatally exposed to 50 mg GBH/kg/day. Moreover, both GBH-exposed groups displayed a significant decrease in the expression of Catalase (Cat – oxidative stress) (49%, p = 0.003; and 31% p = 0.050, respectively) expression, in the cortex. Serum metabolites analyses, from the same animals of each group, demonstrated that there were significant changes in the concentrations of lysophosphatidylcholine and phosphatidylcholine, which have been associated with neurodegenerative diseases. The results of the present study suggest GBH exposure during pregnancy alters the expression of genes associated with oxidant defense, inflammation and lipid metabolism. It is plausible that maternal GBH exposure could have lasting neuronal effects on the offspring later in life.