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. 2021 Jul 6;75(12):1710–1722. doi: 10.1038/s41430-021-00905-6

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — A, B Increased DNA methylation and reciprocally decreased DNA hydroxymethylation at pregnancy-associated gene clusters in placentas of obese compared to lean mothers. A GH-CSH gene cluster (located on human chromosome 17q24) analysis demonstrating a reciprocal increase in 5mC and decrease in 5hmC. Differential DNA methylation (5mC, red) and hydroxymethylation (5hmC, blue) were observed at the human growth hormone-chorionic somatomammotropin (hGH/hCS/hPL) gene cluster between epigenomes of lean (LN) and obese (OB) mothers. In contrast, a strong resemblance in respective 5mC and 5hmC profiles was evident outside the GH-CSH gene cluster as shown in the rightmost panel. B PSG gene cluster (located on human chromosome 19q13) analysis demonstrating a reciprocal increase in 5mC and decrease in 5hmC. Genomic features are shown as custom tracks in the UCSC genome browser. TSS transcriptional start sites. Arrowheads in the figures indicate marked differences in 5mC and 5hmC distributions. Distribution of genomic 5mC and 5hmC was performed employing methylated and hydroxymethylated DNA immunoprecipitation (MeDip; hMeDIP). C Venn diagram illustrating overlaps of differentially methylated and hydroxymethylated loci. Extended analysis of MeDIP and hMeDIP data sets leads to the identification of a total of 5645 differentially methylated or hydroxymethylated genes across the entire genome (1548 loci with increased 5mC, 406 loci with decreased 5mC, 1141 loci with increased 5hmC, and 2550 loci with decreased 5hmC in obese vs. lean pregnancies). D Correlation between maternal early pregnancy BMI and placental α-ketoglutarate levels determined by HPLC-ESI-MS. The relationship between the continuous variables was evaluated by Spearman correlation analysis. Reprinted from [33] published under a CC BY 4.0 license.