Prenatal S-Adenosine Methionine (SAMe) Induces Changes in Gene Expression in the Brain of Newborn Mice That Are Prevented by Co-Administration of Valproic Acid (VPA).
Animals
Animals, Newborn
Autism Spectrum Disorder
/ drug therapy
Brain
/ drug effects
Epigenesis, Genetic
/ drug effects
Female
Gene Expression Regulation, Developmental
/ drug effects
Gene Ontology
Male
Mice
Pregnancy
Prenatal Exposure Delayed Effects
/ drug therapy
S-Adenosylmethionine
/ administration & dosage
Signal Transduction
/ drug effects
Transcriptome
Valproic Acid
/ administration & dosage
Vascular Endothelial Growth Factor A
/ drug effects
ASD
NanoString nCounter
SAMe
VPA
epigenetics
gene expression
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
18 Apr 2020
18 Apr 2020
Historique:
received:
25
02
2020
revised:
13
04
2020
accepted:
14
04
2020
entrez:
25
4
2020
pubmed:
25
4
2020
medline:
3
2
2021
Statut:
epublish
Résumé
In previous studies, we produced changes in gene expression in the brain of mice by early postnatal administration of valproic acid (VPA), with distinct differences between genders. The addition of S-adenosine methionine (SAMe) normalized the expression of most genes in both genders, while SAMe alone induced no changes. We treated pregnant dams with a single injection of VPA on day 12.5 of gestation, or with SAMe during gestational days 12-14, or by a combination of VPA and SAMe. In the frontal half of the brain, we studied the expression of 770 genes of the pathways involved in neurophysiology and neuropathology using the NanoString nCounter method. SAMe, but not VPA, induced statistically significant changes in the expression of many genes, with differences between genders. The expression of 112 genes was changed in both sexes, and another 170 genes were changed only in females and 31 only in males. About 30% of the genes were changed by more than 50%. One of the most important pathways changed by SAMe in both sexes was the VEGF (vascular endothelial growth factor) pathway. Pretreatment with VPA prevented almost all the changes in gene expression induced by SAMe. We conclude that large doses of SAMe, if administered prenatally, may induce significant epigenetic changes in the offspring. Hence, SAMe and possibly other methyl donors may be epigenetic teratogens.
Identifiants
pubmed: 32325788
pii: ijms21082834
doi: 10.3390/ijms21082834
pmc: PMC7215397
pii:
doi:
Substances chimiques
Vascular Endothelial Growth Factor A
0
Valproic Acid
614OI1Z5WI
S-Adenosylmethionine
7LP2MPO46S
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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