Epigenetic modification of the pentose phosphate pathway and the IGF-axis in women with gestational diabetes mellitus

Steyn, Angela; Crowther, Nigel J.; Norris, Shane A.; Rabionet Janssen, Raquel; Estivill, Xavier, 1955-; Ramsay, Michèle

doi:http://dx.doi.org/10.2217/epi-2018-0206

Epigenetic modification of the pentose phosphate pathway and the IGF-axis in women with gestational diabetes mellitus

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Steyn A, Crowther NJ, Norris SA, Rabionet R, Estivill X, Ramsay M. Epigenetic modification of the pentose phosphate pathway and the IGF-axis in women with gestational diabetes mellitus. Epigenomics. 2019; 11(12):1371-85. DOI: 10.2217/epi-2018-0206

Abstract

Aim: Gestational diabetes mellitus (GDM) has been linked with adverse long-term health outcomes for the fetus and mother. These effects may be mediated by epigenetic modifications. Materials & methods: Genome-wide RNA sequencing was performed in placental tissue and maternal blood in six GDM and six non-GDM pregnancies. Promoter region DNA methylation was examined for selected genes and correlated with gene expression to examine an epigenetic modulator mechanism. Results: Reductions of mRNA expression and increases in promoter methylation were observed for G6PD in GDM women, and for genes encoding IGF-binding proteins in GDM-exposed placenta. Conclusion: GDM involves epigenetic attenuation of G6PD, which may lead to hyperglycemia and oxidative stress, and the IGF-axis, which may modulate fetal macrosomia.