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)
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 alon...
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MDPI AG
2020-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/8/2834 |
| _version_ | 1797570276054007808 |
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| author | Liza Weinstein-Fudim Zivanit Ergaz Moshe Szyf Asher Ornoy |
| author_facet | Liza Weinstein-Fudim Zivanit Ergaz Moshe Szyf Asher Ornoy |
| author_sort | Liza Weinstein-Fudim |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T20:22:37Z |
| format | Article |
| id | doaj.art-cbbb3edd651d4496a2ccb4b4e71b0daa |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:22:37Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cbbb3edd651d4496a2ccb4b4e71b0daa2023-11-19T22:04:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01218283410.3390/ijms21082834Prenatal 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)Liza Weinstein-Fudim0Zivanit Ergaz1Moshe Szyf2Asher Ornoy3Department of Medical Neurobiology, Hebrew University Hadassah Medical School, Jerusalem 911200, IsraelDepartment of Medical Neurobiology, Hebrew University Hadassah Medical School, Jerusalem 911200, IsraelDepartment of Pharmacology and Therapeutics, McGill University Medical School, Montreal, QC H3A 2R7, CanadaDepartment of Medical Neurobiology, Hebrew University Hadassah Medical School, Jerusalem 911200, IsraelIn 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.https://www.mdpi.com/1422-0067/21/8/2834ASDepigeneticsSAMeVPAgene expressionNanoString nCounter |
| spellingShingle | Liza Weinstein-Fudim Zivanit Ergaz Moshe Szyf Asher Ornoy 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) International Journal of Molecular Sciences ASD epigenetics SAMe VPA gene expression NanoString nCounter |
| title | 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) |
| title_full | 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) |
| title_fullStr | 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) |
| title_full_unstemmed | 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) |
| title_short | 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) |
| title_sort | 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 |
| topic | ASD epigenetics SAMe VPA gene expression NanoString nCounter |
| url | https://www.mdpi.com/1422-0067/21/8/2834 |
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