Dataset Information

Up-regulated expression and aberrant DNA methylation of LEP and SH3PXD2A in pre-eclampsia.

ABSTRACT: The primary mechanism underlying pre-eclampsia (PE) remains one of the most burning problems in the obstetrics and gynecology. In this study, we performed an expression profiling screen and detected 1312 genes that were differentially expressed (p<0.05 and fold change >1.5) in PE placentas, including LEP and SH3PXD2A. After validating the microarray results, we conducted the quantitative methylation analysis of LEP and SH3PXD2A in preeclamptic (n?=?16) versus normal placentas (n?=?16). Our results showed that many CpG sites close to the transcriptional start site (TSS) of LEP gene were hypomethylated in placentas from pregnancies with PE compared with those of in controls, including the TSS position (p?=?0.001), the binding sites of Sp1 (p?=?1.57×10(-4)), LP1 (p?=?0.023) and CEBP? (p?=?0.031). Luciferase reporter analysis confirmed the aberrant methylation of LEP promoter and CEBP? co-transfection had a role in the regulation of gene expression. Our results indicated the aberrant LEP promoter methylation was involved in the development of PE. We did not find a significant methylation differences between groups in the promoter region of SH3PXD2A, however, a CGI region in the gene body (CGI34) presented a higher methylation in preeclamptic placentas (p?=?1.57×10(-4)), which might promote the efficiency of gene transcription. We speculated that SH3PXD2A may take part in the pathogenesis of PE through its role in the regulation of trophoblast cell invasion in the period of placenta formation.

SUBMITTER: Xiang Y

PROVIDER: S-EPMC3609796 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Up-regulated expression and aberrant DNA methylation of LEP and SH3PXD2A in pre-eclampsia.

Xiang Yuqian Y Cheng Yan Y Li Xiaotian X Li Qiaoli Q Xu Jiawei J Zhang Junyu J Liu Yun Y Xing Qinghe Q Wang Lei L He Lin L Zhao Xinzhi X

PloS one 20130327 3

The primary mechanism underlying pre-eclampsia (PE) remains one of the most burning problems in the obstetrics and gynecology. In this study, we performed an expression profiling screen and detected 1312 genes that were differentially expressed (p<0.05 and fold change >1.5) in PE placentas, including LEP and SH3PXD2A. After validating the microarray results, we conducted the quantitative methylation analysis of LEP and SH3PXD2A in preeclamptic (n = 16) versus normal placentas (n = 16). Our resul ...[more]

PMID: 23544093

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Project description:Placental cortisol is inactivated in normotensive pregnancies, but is frequently present in pre-eclampsia associated placentae. Since glucocorticoids are strongly associated with the programming of long-term health, we assessed DNA methylation of genes involved in cortisol signalling and bioavailability, and hormonal signalling in the placenta of normotensive and hypertensive pregnancies. Candidate genes/CpG sites were selected through analysis of Illumina Infinium HumanMethylation450 BeadChip array data on control (n?=?19) and early onset pre-eclampsia (EOPET; n?=?19) placental samples. DNA methylation was further quantified by bisulfite pyrosequencing in a larger cohort of control (n?=?111) cases, in addition to EOPET (n?=?19), late onset pre-eclampsia (LOPET; n?=?18) and normotensive intrauterine growth restriction (nIUGR; n?=?13) cases. DNA methylation (percentage points) was increased at CpG sites within genes encoding the glucocorticoid receptor (NR3C1 exon 1D promoter; +8.46%; P<0.01) and corticotropin releasing hormone (CRH) binding protein (CRHBP intron 3; +9.14%; P<0.05), and decreased within CRH (5' UTR; -4.30%; P?=?0.11) in EOPET-associated placentae, but not in LOPET nor nIUGR cases, compared to controls. Differential DNA methylation was not observed among groups at the 11?-hydroxysteroid dehydrogenase type 2 (HSD11B2) gene promoter. Significant hypomethylation was observed in pre-eclampsia but not nIUGR placentae for steroidogenic genes, including CYP11A1 (exon1; EOPET; -9.66%; P<0.00001, and LOPET; -5.77%; P<0.001), 3?-hydroxy-delta-5-steroid dehydrogenase type 1 (HSD3B1 exon 2; EOPET; -12.49%; P<0.00001, and LOPET; -6.88%; P<0.001), TEA domain family member 3 (TEAD3 intron 1; EOPET; -12.56%; P<0.00001) and CYP19 (placental-specific exon 1.1 promoter; EOPET; -10.62%, P<0.0001). These data represent dysregulation of the placental epigenome in pre-eclampsia related to genes involved in maintaining the hormonal environment during pregnancy and highlights particular susceptibility in the early onset syndrome.

Dataset Information

Up-regulated expression and aberrant DNA methylation of LEP and SH3PXD2A in pre-eclampsia.

Publications

Up-regulated expression and aberrant DNA methylation of LEP and SH3PXD2A in pre-eclampsia.

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