Insulin-like growth factor axis in pregnancies affected by fetal growth disorders

Nawathe, A.R., Christian, M. ORCID: 0000-0002-1616-4179, Kim, S.H., Johnson, M., Savvidou, M.D. and Terzidou, V., 2016. Insulin-like growth factor axis in pregnancies affected by fetal growth disorders. Clinical Epigenetics, 8 (1): 11. ISSN 1868-7075

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Abstract

Background: Insulin-like growth factors 1 and 2 (IGF1 and IGF2) and their binding proteins (IGFBPs) are expressed in the placenta and known to regulate fetal growth. DNA methylation is an epigenetic mechanism which involves addition of methyl group to a cytosine base in the DNA forming a methylated cytosine-phosphate-guanine (CpG) dinucleotide which is known to silence gene expression. This silences gene expression, potentially altering the expression of IGFs and their binding proteins. This study investigates the relationship between DNA methylation of components of the IGF axis in the placenta and disorders in fetal growth. Placental samples were obtained from cord insertions immediately after delivery from appropriate, small (defined as birthweight <10th percentile for the gestation [SGA]) and macrosomic (defined as birthweight > the 90th percentile for the gestation [LGA]) neonates. Placental DNA methylation, mRNA expression and protein levels of components of the IGF axis were determined by pyrosequencing, rtPCR and Western blotting.

Results: In the placenta from small for gestational age (SGA) neonates (n = 16), mRNA and protein levels of IGF1 were lower and of IGFBPs (1, 2, 3, 4 and 7) were higher (p < 0.05) compared to appropriately grown neonates (n = 37). In contrast, in the placenta from large for gestational age (LGA) neonates (n = 20), mRNA and protein levels of IGF1 was not different and those of IGFBPs (1, 2, 3 and 4) were lower (p < 0.05) compared to appropriately grown neonates. Compared to appropriately grown neonates, CpG methylation of the promoter regions of IGF1 was higher in SGA neonates. The CpG methylation of the promoter regions of IGFBP1, IGFBP2, IGFBP3, IGFBP4 and IGFBP7 was lower in the placenta from SGA neonates as compared to appropriately grown neonates, but was unchanged in the placenta from LGA neonates.

Conclusions: Our results suggest that changes in CpG methylation contribute to the changes in gene expression of components of the IGF axis in fetal growth disorders. Differential methylation of the IGF1 gene and its binding proteins is likely to play a role in the pathogenesis of SGA neonates.

Item Type: Journal article
Publication Title: Clinical Epigenetics
Creators: Nawathe, A.R., Christian, M., Kim, S.H., Johnson, M., Savvidou, M.D. and Terzidou, V.
Publisher: BioMed Central
Date: 2016
Volume: 8
Number: 1
ISSN: 1868-7075
Identifiers:
NumberType
10.1186/s13148-016-0178-5DOI
178Publisher Item Identifier
Rights: © 2016 Nawathe et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Divisions: Schools > School of Science and Technology
Depositing User: Linda Sullivan
Date Added: 08 Aug 2019 15:37
Last Modified: 08 Aug 2019 15:37
URI: http://irep.ntu.ac.uk/id/eprint/37201

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