Enrichment of trimethyl histone 3 lysine 4 in the Dlk1 and Grb10 genes affects pregnancy outcomes due to dietary manipulation of excess folic acid and low vitamin B12
Abstract The aberrant expression of placental imprinted genes due to epigenetic alterations during pregnancy can impact fetal development. We investigated the impact of dietary modification of low vitamin B12 with varying doses of folic acid on the epigenetic control of imprinted genes and fetal dev...
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2024-11-01
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| Online Access: | https://doi.org/10.1186/s40659-024-00557-3 |
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| author | Divika Sapehia Aatish Mahajan Parampal Singh Jyotdeep Kaur |
| author_facet | Divika Sapehia Aatish Mahajan Parampal Singh Jyotdeep Kaur |
| author_sort | Divika Sapehia |
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| description | Abstract The aberrant expression of placental imprinted genes due to epigenetic alterations during pregnancy can impact fetal development. We investigated the impact of dietary modification of low vitamin B12 with varying doses of folic acid on the epigenetic control of imprinted genes and fetal development using a transgenerational model of C57BL/6J mice. The animals were kept on four distinct dietary combinations based on low vitamin B12 levels and modulated folic acid, mated in the F0 generation within each group. In the F1 generation, each group of mice is split into two subgroups; the sustained group was kept on the same diet, while the transient group was fed a regular control diet. After mating, maternal placenta (F1) and fetal tissues (F2) were isolated on day 20 of gestation. We observed a generation-wise opposite promoter CpG methylation and gene expression trend of the two developmental genes Dlk1 and Grb10, with enhanced gene expression in both the sustained and transient experimental groups in F1 placentae. When fetal development characteristics and gene expression were correlated, there was a substantial negative association between placental weight and Dlk1 expression (r = − 0.49, p < 0.05) and between crown-rump length and Grb10 expression (r = − 0.501, p < 0.05) in fetuses of the F2 generation. Consistent with these results, we also found that H3K4me3 at the promoter level of these genes is negatively associated with all fetal growth parameters. Overall, our findings suggest that balancing vitamin B12 and folic acid levels is important for maintaining the transcriptional status of imprinted genes and fetal development. |
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| institution | Kabale University |
| issn | 0717-6287 |
| language | English |
| publishDate | 2024-11-01 |
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| spelling | doaj-art-30ddb9b64d6e490c9876dfc1c5428eba2024-11-17T12:10:32ZengBMCBiological Research0717-62872024-11-0157111510.1186/s40659-024-00557-3Enrichment of trimethyl histone 3 lysine 4 in the Dlk1 and Grb10 genes affects pregnancy outcomes due to dietary manipulation of excess folic acid and low vitamin B12Divika Sapehia0Aatish Mahajan1Parampal Singh2Jyotdeep Kaur3Department of Biochemistry, Postgraduate Institute of Medical Education and ResearchDepartment of Biochemistry, Postgraduate Institute of Medical Education and ResearchDepartment of Biochemistry, Postgraduate Institute of Medical Education and ResearchDepartment of Biochemistry, Postgraduate Institute of Medical Education and ResearchAbstract The aberrant expression of placental imprinted genes due to epigenetic alterations during pregnancy can impact fetal development. We investigated the impact of dietary modification of low vitamin B12 with varying doses of folic acid on the epigenetic control of imprinted genes and fetal development using a transgenerational model of C57BL/6J mice. The animals were kept on four distinct dietary combinations based on low vitamin B12 levels and modulated folic acid, mated in the F0 generation within each group. In the F1 generation, each group of mice is split into two subgroups; the sustained group was kept on the same diet, while the transient group was fed a regular control diet. After mating, maternal placenta (F1) and fetal tissues (F2) were isolated on day 20 of gestation. We observed a generation-wise opposite promoter CpG methylation and gene expression trend of the two developmental genes Dlk1 and Grb10, with enhanced gene expression in both the sustained and transient experimental groups in F1 placentae. When fetal development characteristics and gene expression were correlated, there was a substantial negative association between placental weight and Dlk1 expression (r = − 0.49, p < 0.05) and between crown-rump length and Grb10 expression (r = − 0.501, p < 0.05) in fetuses of the F2 generation. Consistent with these results, we also found that H3K4me3 at the promoter level of these genes is negatively associated with all fetal growth parameters. Overall, our findings suggest that balancing vitamin B12 and folic acid levels is important for maintaining the transcriptional status of imprinted genes and fetal development.https://doi.org/10.1186/s40659-024-00557-3Vitamin B12Folic acidPlacentaTransgenerationalHistone methylation |
| spellingShingle | Divika Sapehia Aatish Mahajan Parampal Singh Jyotdeep Kaur Enrichment of trimethyl histone 3 lysine 4 in the Dlk1 and Grb10 genes affects pregnancy outcomes due to dietary manipulation of excess folic acid and low vitamin B12 Biological Research Vitamin B12 Folic acid Placenta Transgenerational Histone methylation |
| title | Enrichment of trimethyl histone 3 lysine 4 in the Dlk1 and Grb10 genes affects pregnancy outcomes due to dietary manipulation of excess folic acid and low vitamin B12 |
| title_full | Enrichment of trimethyl histone 3 lysine 4 in the Dlk1 and Grb10 genes affects pregnancy outcomes due to dietary manipulation of excess folic acid and low vitamin B12 |
| title_fullStr | Enrichment of trimethyl histone 3 lysine 4 in the Dlk1 and Grb10 genes affects pregnancy outcomes due to dietary manipulation of excess folic acid and low vitamin B12 |
| title_full_unstemmed | Enrichment of trimethyl histone 3 lysine 4 in the Dlk1 and Grb10 genes affects pregnancy outcomes due to dietary manipulation of excess folic acid and low vitamin B12 |
| title_short | Enrichment of trimethyl histone 3 lysine 4 in the Dlk1 and Grb10 genes affects pregnancy outcomes due to dietary manipulation of excess folic acid and low vitamin B12 |
| title_sort | enrichment of trimethyl histone 3 lysine 4 in the dlk1 and grb10 genes affects pregnancy outcomes due to dietary manipulation of excess folic acid and low vitamin b12 |
| topic | Vitamin B12 Folic acid Placenta Transgenerational Histone methylation |
| url | https://doi.org/10.1186/s40659-024-00557-3 |
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