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Different dietary combinations of folic acid and vitamin B12 in parental diet results in epigenetic reprogramming of IGF2R and KCNQ1OT1 in placenta and fetal tissues in mice.
Mol Reprod Dev. 2021 06; 88(6):437-458.MR

Abstract

Genomic imprinting is important for mammalian development and its dysregulation can cause various developmental defects and diseases. The study evaluated the effects of different dietary combinations of folic acid and B12 on epigenetic regulation of IGF2R and KCNQ1OT1 ncRNA in C57BL/6 mice model. Female mice were fed diets with nine combinations of folic acid and B12 for 4 weeks. They were mated and off-springs born (F1) were continued on the same diet for 6 weeks postweaning and were allowed to mate. The placenta and fetal (F2) tissues were collected at day 20 of gestation. Dietary deficiency of folate (BNFD and BOFD) and B12 (BDFN) with either state of other vitamin or combined deficiency of both vitamins (BDFD) in comparison to BNFN, were overall responsible for reduced expression of IGF2R in the placenta (F1) and the fetal liver (F2) whereas a combination of folate deficiency with different levels of B12 revealed sex-specific differences in kidney and brain. The alterations in the expression of IGF2R caused by folate-deficient conditions (BNFD and BOFD) and both deficient condition (BDFD) was found to be associated with an increase in suppressive histone modifications. Over-supplementation of either folate or B12 or both vitamins in comparison to BNFN, led to increase in expression of IGF2R and KCNQ1OT1 in the placenta and fetal tissues. The increase in the expression of IGF2R caused by folate over-supplementation (BNFO) was associated with decreased DNA methylation in fetal tissues. KCNQ1OT1 noncoding RNA (ncRNA), however, showed upregulation under deficient conditions of folate and B12 only in female fetal tissues which correlated well with hypomethylation observed under these conditions. An epigenetic reprograming of IGF2R and KCNQ1OT1 ncRNA in the offspring was evident upon different dietary combinations of folic acid and B12 in the mice.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Mahajan A
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Sapehia D
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Bagga R
Department of Obstetrics and Gynecology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Kaur J
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

MeSH

AnimalsBody WeightBrainDietDose-Response Relationship, DrugDrug InteractionsEpigenesis, GeneticFemaleFetusFolic AcidFolic Acid DeficiencyGene Expression Regulation, DevelopmentalGenomic ImprintingHomocysteineKidneyLiverMaleMicePlacentaPregnancyPregnancy ComplicationsRNA, Long NoncodingRNA, MessengerReceptor, IGF Type 2Vitamin B 12Vitamin B 12 Deficiency

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34008284

Citation

Mahajan, Aatish, et al. "Different Dietary Combinations of Folic Acid and Vitamin B12 in Parental Diet Results in Epigenetic Reprogramming of IGF2R and KCNQ1OT1 in Placenta and Fetal Tissues in Mice." Molecular Reproduction and Development, vol. 88, no. 6, 2021, pp. 437-458.
Mahajan A, Sapehia D, Bagga R, et al. Different dietary combinations of folic acid and vitamin B12 in parental diet results in epigenetic reprogramming of IGF2R and KCNQ1OT1 in placenta and fetal tissues in mice. Mol Reprod Dev. 2021;88(6):437-458.
Mahajan, A., Sapehia, D., Bagga, R., & Kaur, J. (2021). Different dietary combinations of folic acid and vitamin B12 in parental diet results in epigenetic reprogramming of IGF2R and KCNQ1OT1 in placenta and fetal tissues in mice. Molecular Reproduction and Development, 88(6), 437-458. https://doi.org/10.1002/mrd.23477
Mahajan A, et al. Different Dietary Combinations of Folic Acid and Vitamin B12 in Parental Diet Results in Epigenetic Reprogramming of IGF2R and KCNQ1OT1 in Placenta and Fetal Tissues in Mice. Mol Reprod Dev. 2021;88(6):437-458. PubMed PMID: 34008284.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Different dietary combinations of folic acid and vitamin B12 in parental diet results in epigenetic reprogramming of IGF2R and KCNQ1OT1 in placenta and fetal tissues in mice. AU - Mahajan,Aatish, AU - Sapehia,Divika, AU - Bagga,Rashmi, AU - Kaur,Jyotdeep, Y1 - 2021/05/18/ PY - 2021/04/28/revised PY - 2020/10/10/received PY - 2021/04/30/accepted PY - 2021/5/20/pubmed PY - 2022/1/15/medline PY - 2021/5/19/entrez KW - DNA methylation KW - epigenetics KW - folate KW - genomic imprinting KW - vitamin B12 SP - 437 EP - 458 JF - Molecular reproduction and development JO - Mol Reprod Dev VL - 88 IS - 6 N2 - Genomic imprinting is important for mammalian development and its dysregulation can cause various developmental defects and diseases. The study evaluated the effects of different dietary combinations of folic acid and B12 on epigenetic regulation of IGF2R and KCNQ1OT1 ncRNA in C57BL/6 mice model. Female mice were fed diets with nine combinations of folic acid and B12 for 4 weeks. They were mated and off-springs born (F1) were continued on the same diet for 6 weeks postweaning and were allowed to mate. The placenta and fetal (F2) tissues were collected at day 20 of gestation. Dietary deficiency of folate (BNFD and BOFD) and B12 (BDFN) with either state of other vitamin or combined deficiency of both vitamins (BDFD) in comparison to BNFN, were overall responsible for reduced expression of IGF2R in the placenta (F1) and the fetal liver (F2) whereas a combination of folate deficiency with different levels of B12 revealed sex-specific differences in kidney and brain. The alterations in the expression of IGF2R caused by folate-deficient conditions (BNFD and BOFD) and both deficient condition (BDFD) was found to be associated with an increase in suppressive histone modifications. Over-supplementation of either folate or B12 or both vitamins in comparison to BNFN, led to increase in expression of IGF2R and KCNQ1OT1 in the placenta and fetal tissues. The increase in the expression of IGF2R caused by folate over-supplementation (BNFO) was associated with decreased DNA methylation in fetal tissues. KCNQ1OT1 noncoding RNA (ncRNA), however, showed upregulation under deficient conditions of folate and B12 only in female fetal tissues which correlated well with hypomethylation observed under these conditions. An epigenetic reprograming of IGF2R and KCNQ1OT1 ncRNA in the offspring was evident upon different dietary combinations of folic acid and B12 in the mice. SN - 1098-2795 UR - https://www.unboundmedicine.com/medline/citation/34008284/Different_dietary_combinations_of_folic_acid_and_vitamin_B12_in_parental_diet_results_in_epigenetic_reprogramming_of_IGF2R_and_KCNQ1OT1_in_placenta_and_fetal_tissues_in_mice_ DB - PRIME DP - Unbound Medicine ER -