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Placental DNA methylation changes in gestational diabetes mellitus.

ABSTRACT: In this study, we investigated the association between altered methylation in the maternal placenta and hyperglycaemia and explored the epigenetic mechanisms underlying gestational diabetes mellitus (GDM). Reduced representation bisulphite sequencing (RRBS) and RNA sequencing (RNA-seq) were performed on placental tissues obtained from women with GDM and healthy controls. Further, pyrosequencing, correlation analyses, and linear regression analyses were performed to valuate relationships between aberrantly methylated-differentially expressed genes and clinical parameters. The EMBOSS and JASPAR databases were used for a computational analysis of CpG islands and transcription factor-binding sites in the TRIM67 promoter region. A CpG island with a length of 264 bp in the placental TRIM67 promoter region in the GDM group exhibited significant hypermethylation at four CpG sites. The hypermethylation of the TRIM67 promoter region in the maternal placenta showed a significant, positive correlation with the 1 h and 2 h oral glucose tolerance test (OGTT) values and a negative correlation with lipoprotein(a). Placental DNA methylation levels in the TRIM67 promoter region were markedly elevated in GDM and were associated with blood glucose and lipid levels during healthy pregnancy.

SUBMITTER: Chen F

PROVIDER: S-EPMC9665131 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Placental DNA methylation changes in gestational diabetes mellitus.

Chen Fujia F Fei Xiaoping X Zhu Weiqiang W Zhang Zhaofeng Z Shen Yupei Y Mao Yanyan Y Zhu Qianxi Q Xu Jianhua J Zhou Weijin W Li Min M Du Jing J

Epigenetics 20220821 13

In this study, we investigated the association between altered methylation in the maternal placenta and hyperglycaemia and explored the epigenetic mechanisms underlying gestational diabetes mellitus (GDM). Reduced representation bisulphite sequencing (RRBS) and RNA sequencing (RNA-seq) were performed on placental tissues obtained from women with GDM and healthy controls. Further, pyrosequencing, correlation analyses, and linear regression analyses were performed to valuate relationships between ...[more]

PMID: 35993280

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Project description:BackgroundMaternal obesity prior to or during pregnancy influences fetal growth, predisposing the offspring to increased risk for obesity across the life course. Placental epigenetic mechanisms may underlie these associations. We conducted an epigenome-wide association study to identify placental DNA methylation changes associated with maternal prepregnancy body mass index (BMI) and rate of gestational weight gain at first (GWG1), second (GWG2), and third trimester (GWG3).MethodParticipants of the NICHD Fetal Growth Studies with genome-wide placental DNA methylation (n = 301) and gene expression (n = 75) data were included. Multivariable-adjusted regression models were used to test the associations of 1 kg/m2 increase in prepregnancy BMI or 1 kg/week increase in GWG with DNA methylation levels. Genes harboring top differentially methylated CpGs (FDR P < 0.05) were evaluated for placental gene expression. We assessed whether DNA methylation sites known to be associated with BMI in child or adult tissues, were also associated with maternal prepregnancy BMI in placenta.ResultsPrepregnancy BMI was associated with DNA methylation at cg14568196[EGFL7], cg15339142[VETZ], and cg02301019[AC092377.1] (FDR P < 0.05, P ranging from 1.4 × 10-10 to 1.7 × 10-9). GWG1 or GWG2 was associated with DNA methylation at cg17918270[MYT1L], cg20735365[DLX5], and cg17451688[SLC35F3] (FDR P < 0.05, P ranging from 6.4 × 10-10 to 1.2 × 10-8). Both prepregnancy BMI and DNA methylation at cg1456819 [EGFL7] were negatively correlated with EGFL7 expression in placenta (P < 0.05). Several CpGs previously implicated in obesity traits in children and adults were associated with prepregnancy BMI in placenta. Functional annotations revealed that EGFL7 is highly expressed in placenta and the differentially methylated CpG sites near EGFL7 and VEZT were cis-meQTL targets in blood.ConclusionsWe identified placental DNA methylation changes at novel loci associated with prepregnancy BMI and GWG. The overlap between CpGs associated with obesity traits in placenta and other tissues in children and adults suggests that epigenetic mechanisms in placenta may give insights to early origins of obesity.

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Placental DNA methylation changes in gestational diabetes mellitus.

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Placental DNA methylation changes in gestational diabetes mellitus.

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