PMID- 31226268
OWN - NLM
STAT- MEDLINE
DCOM- 20200512
LR  - 20231213
IS  - 1872-9711 (Electronic)
IS  - 0161-813X (Linking)
VI  - 74
DP  - 2019 Sep
TI  - Maternal glyphosate-based herbicide exposure alters antioxidant-related genes in 
      the brain and serum metabolites of male rat offspring.
PG  - 121-131
LID - S0161-813X(18)30520-5 [pii]
LID - 10.1016/j.neuro.2019.06.004 [doi]
AB  - 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 (Hif1alpha - 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.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - de Souza, Janaina Sena
AU  - de Souza JS
AD  - Universidade Federal de Sao Paulo, UNIFESP/EPM, Departamento de Medicina, 
      Disciplina de Endocrinologia Clinica, Sao Paulo, Sao Paulo, 04039-032, Brazil. 
      Electronic address: janaina.sena@unifesp.br.
FAU - Laureano-Melo, Roberto
AU  - Laureano-Melo R
AD  - Universidade Federal de Sao Paulo, UNIFESP/EPM, Departamento de Medicina, 
      Disciplina de Endocrinologia Clinica, Sao Paulo, Sao Paulo, 04039-032, Brazil.
FAU - Herai, Roberto Hirochi
AU  - Herai RH
AD  - Pontificia Universidade Catolica do Parana, School of Medicine, Graduate Program 
      in Health Sciences (PUCPR/PPGCS), Curitiba, Parana, 80215-901, Brazil; Instituto 
      Lico Kaesemodel (ILK), Curitiba, Parana, 80240-000, Brazil.
FAU - da Conceicao, Rodrigo Rodrigues
AU  - da Conceicao RR
AD  - Universidade Federal de Sao Paulo, UNIFESP/EPM, Departamento de Medicina, 
      Disciplina de Endocrinologia Clinica, Sao Paulo, Sao Paulo, 04039-032, Brazil.
FAU - Oliveira, Kelen Carneiro
AU  - Oliveira KC
AD  - Universidade Federal de Sao Paulo, UNIFESP/EPM, Departamento de Medicina, 
      Disciplina de Endocrinologia Clinica, Sao Paulo, Sao Paulo, 04039-032, Brazil.
FAU - da Silva, Ismael Dale Cotrim Guerreiro
AU  - da Silva IDCG
AD  - Universidade Federal de Sao Paulo, UNIFESP/EPM, Departamento de Ginecologia, Sao 
      Paulo, Sao Paulo, 04039-032, Brazil.
FAU - Dias-da-Silva, Magnus Regios
AU  - Dias-da-Silva MR
AD  - Universidade Federal de Sao Paulo, UNIFESP/EPM, Departamento de Medicina, 
      Disciplina de Endocrinologia Clinica, Sao Paulo, Sao Paulo, 04039-032, Brazil.
FAU - Romano, Renata Marino
AU  - Romano RM
AD  - Universidade Estadual do Centro-Oeste, Departamento de Farmacia, Guarapuava, 
      Parana, Brazil.
FAU - Romano, Marco Aurelio
AU  - Romano MA
AD  - Universidade Estadual do Centro-Oeste, Departamento de Farmacia, Guarapuava, 
      Parana, Brazil.
FAU - Maciel, Rui Monteiro de Barros
AU  - Maciel RMB
AD  - Universidade Federal de Sao Paulo, UNIFESP/EPM, Departamento de Medicina, 
      Disciplina de Endocrinologia Clinica, Sao Paulo, Sao Paulo, 04039-032, Brazil.
FAU - Chiamolera, Maria Izabel
AU  - Chiamolera MI
AD  - Universidade Federal de Sao Paulo, UNIFESP/EPM, Departamento de Medicina, 
      Disciplina de Endocrinologia Clinica, Sao Paulo, Sao Paulo, 04039-032, Brazil.
FAU - Giannocco, Gisele
AU  - Giannocco G
AD  - Universidade Federal de Sao Paulo, UNIFESP/EPM, Departamento de Medicina, 
      Disciplina de Endocrinologia Clinica, Sao Paulo, Sao Paulo, 04039-032, Brazil; 
      Universidade Federal de Sao Paulo, Departamento de Ciencias Biologicas, Diadema, 
      Sao Paulo, 09972-270, Brazil. Electronic address: ggiannocco@unifesp.br.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190618
PL  - Netherlands
TA  - Neurotoxicology
JT  - Neurotoxicology
JID - 7905589
RN  - 0 (Antioxidants)
RN  - 0 (Herbicides)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Animals
MH  - Antioxidants/*metabolism
MH  - Brain Chemistry/*drug effects/*genetics
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Gene Regulatory Networks/drug effects
MH  - Gestational Age
MH  - Glycine/*analogs & derivatives/toxicity
MH  - Herbicides/*toxicity
MH  - Inflammation/chemically induced/genetics/pathology
MH  - Lipid Metabolism/drug effects/genetics
MH  - Male
MH  - Maternal Exposure/*adverse effects
MH  - Metabolome/drug effects
MH  - Oxidative Stress/drug effects
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/genetics
MH  - Rats
MH  - Rats, Wistar
MH  - Glyphosate
OTO - NOTNLM
OT  - Antioxidant enzymes
OT  - Gene expression
OT  - Glyphosate-based herbicide
OT  - Inflammation
OT  - Metabolomics
OT  - Oxidative stress
EDAT- 2019/06/22 06:00
MHDA- 2020/05/13 06:00
CRDT- 2019/06/22 06:00
PHST- 2018/12/14 00:00 [received]
PHST- 2019/05/31 00:00 [revised]
PHST- 2019/06/14 00:00 [accepted]
PHST- 2019/06/22 06:00 [pubmed]
PHST- 2020/05/13 06:00 [medline]
PHST- 2019/06/22 06:00 [entrez]
AID - S0161-813X(18)30520-5 [pii]
AID - 10.1016/j.neuro.2019.06.004 [doi]
PST - ppublish
SO  - Neurotoxicology. 2019 Sep;74:121-131. doi: 10.1016/j.neuro.2019.06.004. Epub 2019 
      Jun 18.