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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.

Titel:	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).
Autor/in / Beteiligte Person:	Weinstein-Fudim, L ; Ergaz, Z ; Szyf, M ; Ornoy, A
Link:	Zum Volltext
Zeitschrift:	International journal of molecular sciences, Jg. 21 (2020-04-18), Heft 8
Veröffentlichung:	Basel, Switzerland : MDPI, [2000-, 2020
Medientyp:	academicJournal
ISSN:	1422-0067 (electronic)
DOI:	10.3390/ijms21082834
Schlagwort:	Animals Animals, Newborn Autism Spectrum Disorder metabolism Brain metabolism Epigenesis, Genetic drug effects Female Gene Expression Regulation, Developmental drug effects Gene Expression Regulation, Developmental genetics Gene Ontology Male Mice Pregnancy Prenatal Exposure Delayed Effects drug therapy S-Adenosylmethionine metabolism Signal Transduction genetics Transcriptome Vascular Endothelial Growth Factor A drug effects Vascular Endothelial Growth Factor A genetics Autism Spectrum Disorder drug therapy Brain drug effects Prenatal Exposure Delayed Effects metabolism S-Adenosylmethionine administration & dosage Signal Transduction drug effects Valproic Acid administration & dosage Vascular Endothelial Growth Factor A metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Int J Mol Sci] 2020 Apr 18; Vol. 21 (8). <i>Date of Electronic Publication: </i>2020 Apr 18. MeSH Terms: Autism Spectrum Disorder / drug therapy ; Brain / drug effects ; Prenatal Exposure Delayed Effects / metabolism ; S-Adenosylmethionine / administration & dosage ; Signal Transduction / drug effects ; Valproic Acid / administration & dosage ; Vascular Endothelial Growth Factor A / *metabolism ; Animals ; Animals, Newborn ; Autism Spectrum Disorder / metabolism ; Brain / metabolism ; Epigenesis, Genetic / drug effects ; Female ; Gene Expression Regulation, Developmental / drug effects ; Gene Expression Regulation, Developmental / genetics ; Gene Ontology ; Male ; Mice ; Pregnancy ; Prenatal Exposure Delayed Effects / drug therapy ; S-Adenosylmethionine / metabolism ; Signal Transduction / genetics ; Transcriptome ; Vascular Endothelial Growth Factor A / drug effects ; Vascular Endothelial Growth Factor A / genetics References: FASEB J. 2017 Jun;31(6):2352-2363. (PMID: 28209774) ; Psychopharmacology (Berl). 2020 Jan;237(1):209-218. 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(PMID: 25300468) ; Epigenomics. 2015;7(8):1259-74. (PMID: 26178076) Contributed Indexing: Keywords: ASD; NanoString nCounter; SAMe; VPA; epigenetics; gene expression Substance Nomenclature: 0 (Vascular Endothelial Growth Factor A) ; 614OI1Z5WI (Valproic Acid) ; 7LP2MPO46S (S-Adenosylmethionine) Entry Date(s): Date Created: 20200425 Date Completed: 20210202 Latest Revision: 20210202 Update Code: 20231215 PubMed Central ID: PMC7215397

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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).