Maternal glyphosate-based herbicide exposure alters antioxidant-related genes in the brain and serum metabolites of male rat offspring. 2019

Janaina Sena de Souza, and Roberto Laureano-Melo, and Roberto Hirochi Herai, and Rodrigo Rodrigues da Conceição, and Kelen Carneiro Oliveira, and Ismael Dale Cotrim Guerreiro da Silva, and Magnus Régios Dias-da-Silva, and Renata Marino Romano, and Marco Aurélio Romano, and Rui Monteiro de Barros Maciel, and Maria Izabel Chiamolera, and Gisele Giannocco
Universidade Federal de São Paulo, UNIFESP/EPM, Departamento de Medicina, Disciplina de Endocrinologia Clínica, São Paulo, São Paulo, 04039-032, Brazil. Electronic address: janaina.sena@unifesp.br.

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.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008297 Male Males
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011297 Prenatal Exposure Delayed Effects The consequences of exposing the FETUS in utero to certain factors, such as NUTRITION PHYSIOLOGICAL PHENOMENA; PHYSIOLOGICAL STRESS; DRUGS; RADIATION; and other physical or chemical factors. These consequences are observed later in the offspring after BIRTH. Delayed Effects, Prenatal Exposure,Late Effects, Prenatal Exposure
D001923 Brain Chemistry Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states. Chemistry, Brain,Brain Chemistries,Chemistries, Brain
D005260 Female Females
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D005865 Gestational Age The age of the conceptus, beginning from the time of FERTILIZATION. In clinical obstetrics, the gestational age is often estimated from the onset of the last MENSTRUATION which is about 2 weeks before OVULATION and fertilization. It is also estimated to begin from fertilization, estrus, coitus, or artificial insemination. Embryologic Age,Fetal Maturity, Chronologic,Chronologic Fetal Maturity,Fetal Age,Maturity, Chronologic Fetal,Age, Embryologic,Age, Fetal,Age, Gestational,Ages, Embryologic,Ages, Fetal,Ages, Gestational,Embryologic Ages,Fetal Ages,Gestational Ages
D005998 Glycine A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. Aminoacetic Acid,Glycine, Monopotassium Salt,Glycine Carbonate (1:1), Monosodium Salt,Glycine Carbonate (2:1), Monolithium Salt,Glycine Carbonate (2:1), Monopotassium Salt,Glycine Carbonate (2:1), Monosodium Salt,Glycine Hydrochloride,Glycine Hydrochloride (2:1),Glycine Phosphate,Glycine Phosphate (1:1),Glycine Sulfate (3:1),Glycine, Calcium Salt,Glycine, Calcium Salt (2:1),Glycine, Cobalt Salt,Glycine, Copper Salt,Glycine, Monoammonium Salt,Glycine, Monosodium Salt,Glycine, Sodium Hydrogen Carbonate,Acid, Aminoacetic,Calcium Salt Glycine,Cobalt Salt Glycine,Copper Salt Glycine,Hydrochloride, Glycine,Monoammonium Salt Glycine,Monopotassium Salt Glycine,Monosodium Salt Glycine,Phosphate, Glycine,Salt Glycine, Monoammonium,Salt Glycine, Monopotassium,Salt Glycine, Monosodium
D006540 Herbicides Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses (POACEAE), and woody plants. Some plants develop HERBICIDE RESISTANCE. Algaecide,Algicide,Herbicide,Algaecides,Algicides

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