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

Author(s):Show less -

de Souza, Janaina Sena ^[1] ; Laureano-Melo, Roberto ^[1] ; Herai, Roberto Hirochi ^{[2, 3]} ; da Conceicao, Rodrigo Rodrigues ^[1] ; Oliveira, Kelen Carneiro ^[1] ; Cotrim Guerreiro da Silva, Ismael Dale ^[4] ; Dias-da-Silva, Magnus Regios ^[1] ; Romano, Renata Marino ^[5] ; Romano, Marco Aurelio ^[5] ; de Barros Maciel, Rui Monteiro ^[1] ; Chiamolera, Maria Izabel ^[1] ; Giannocco, Gisele ^{[6, 1]}

Affiliation

^[1] Univ Fed Sao Paulo, UNIFESP EPM, Dept Med, Disciplina Endocrinol Clin, BR-04039032 Sao Paulo, SP - Brazil

^[2] Pontificia Univ Catolica Parana, Sch Med, Grad Program Hlth Sci PUCPR PPGCS, BR-80215901 Curitiba, Parana - Brazil

^[3] ILK, BR-80240000 Curitiba, Parana - Brazil

^[4] Univ Fed Sao Paulo, UNIFESP EPM, Dept Ginecol, BR-04039032 Sao Paulo, SP - Brazil

^[5] Univ Estadual Centro Oeste, Dept Farm, Guarapuava, Parana - Brazil

^[6] Univ Fed Sao Paulo, Dept Ciencias Biol, BR-09972270 Sao Paulo - Brazil

• Document type: Journal article
• Source: NeuroToxicology; v. 74, p. 121-131, SEP 2019.
• Web of Science Citations: 0

Abstract

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 (R), 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 (Hif1 alpha - 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. (AU)

• FAPESP's process: 13/26851-7 - In vivo study of the effects of the endocrine disruptors glyphosate and bisphenol-A on the hypothalamic-pituitary-thyroid axis
• Grantee: Maria Izabel Chiamolera
• Support Opportunities: Regular Research Grants
• FAPESP's process: 17/07053-3 - Effect of thyroid hormone on the brain of 3xTg-AD mice, model of Alzheimer's Disease, on glucose and cholesterol metabolism
• Grantee: Janaína Sena de Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral