Baker, BC, Mackie, FL, Lean, SC et al. (4 more authors) (2017) Placental dysfunction is associated with altered microRNA expression in pregnant women with low folate status. Molecular Nutrition and Food Research, 61 (8). ISSN 1613-4125
Abstract
Scope: Low maternal folate status during pregnancy increases the risk of delivering small for gestational age (SGA) infants, but the mechanistic link between maternal folate status, SGA, and placental dysfunction is unknown. microRNAs (miRNAs) are altered in pregnancy pathologies and by folate in other systems. We hypothesized that low maternal folate status causes placental dysfunction, mediated by altered miRNA expression. Methods and results: A prospective observational study recruited pregnant adolescents and assessed third trimester folate status and placental function. miRNA array, QPCR, and bioinformatics identified placental miRNAs and target genes. Low maternal folate status is associated with higher incidence of SGA infants (28% versus 13%, p < 0.05) and placental dysfunction, including elevated trophoblast proliferation and apoptosis (p < 0.001), reduced amino acid transport (p < 0.01), and altered placental hormones (pregnancy-associated plasma protein A, progesterone, and human placental lactogen). miR-222-3p, miR-141-3p, and miR-34b-5p were upregulated by low folate status (p < 0.05). Bioinformatics predicted a gene network regulating cell turnover. Quantitative PCR demonstrated that key genes in this network (zinc finger E-box binding homeobox 2, v-myc myelocytomatosis viral oncogene homolog (avian), and cyclin-dependent kinase 6) were reduced (p < 0.05) in placentas with low maternal folate status. Conclusion: This study supports that placental dysfunction contributes to impaired fetal growth in women with low folate status and suggests altered placental expression of folate-sensitive miRNAs and target genes as a mechanistic link.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017, The Authors. Molecular Nutrition & Food Research Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution License [https://creativecommons.org/licenses/by/4.0/], which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | fetal growth; folate deficiency; gene expression; microRNA; placental dysfunction |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 18 Jan 2017 17:02 |
Last Modified: | 31 Jan 2020 16:15 |
Published Version: | https://doi.org/10.1002/mnfr.201600646 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/mnfr.201600646 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:110707 |
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