Alteration in methylation level at differential methylated regions of MEST and DLK1 in fetus of preeclampsia

Wang, Xiaoqing; Wan, Ling; Weng, Xiaoling; Xie, Jiamin; Zhang, Aiping; Liu, Yun; Dong, Minyue

doi:10.1080/10641955.2017.1397689

Cited by 9 publications

(7 citation statements)

References 53 publications

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“…PE is associated with hypermethylation of IGF-1 promoter mediated by DNMT1 [15]. The methylation levels are changed at differential methylated regions of MEST and DLK1 in fetus of PE [16]. All the evidences suggest the importance of studying the genetic and epigenetic factors to explore the mechanism and treatment for PE.…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of methylation-mediated transcriptional dysregulation dictate methylation roles in preeclampsia

Zhao

et al. 2020

Hum Genomics

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Background: Preeclampsia (PE) is a heterogeneous, hypertensive disorder of pregnancy, with no robust biomarkers or effective treatments. PE increases the risk of poor outcomes for both the mother and the baby. Methylationmediated transcriptional dysregulation motifs (methTDMs) could contribute the PE development. However, precise functional roles of methTDMs in PE have not been globally described. Methods: Here, we develop a comprehensive and computational pipeline to identify PE-specific methTDMs following TF, gene, methylation expression profile, and experimentally verified TF-gene interactions. Results: The regulation patterns of methTDMs are multiple and complex in PE and contain relax inhibition, intensify inhibition, relax activation, intensify activation, reverse activation, and reverse inhibition. A core module is extracted from global methTDM network to further depict the mechanism of methTDMs in PE. The common and specific features of any two kinds of regulation pattern are also analyzed in PE. Some key methylation sites, TFs, and genes such as IL2RG are identified in PE. Functional analysis shows that methTDMs are associated with immune-, insulin-, and NK cell-related functions. Drug-related network identifies some key drug repurposing candidates such as NADH. Conclusion: Collectively, the study highlighted the effect of methylation on the transcription process in PE. MethTDMs could contribute to identify specific biomarkers and drug repurposing candidates for PE.

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Section: Introductionmentioning

confidence: 99%

Identification and characterization of methylation-mediated transcriptional dysregulation dictate methylation roles in preeclampsia

Zhao

et al. 2020

Hum Genomics

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“…Имеются данные о том, что у детей, рожденных матерями с ПЭ, наблюдается аберрантное алкилирование дифференциально метилированных регионов генов IGF2, DLK1 и MEST, которые влияют на постнатальный онтогенез. Данный процесс способствует развитию ожирения, диабета, гипертонии и других метаболических нарушений в зрелом возрасте [24][25][26].…”

Section: Discussionunclassified

Effect of the Gaba Derivative Succicard on the Lipid and Carbohydrate Metabolism in the Offspring of Rats With Experimental Preeclampsia in Early and Late Ontogeny

Muzyko

Перфилова

Nesterova

et al. 2021

Farm. farmakol. (Pâtigorsk)

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Maternal preeclampsia can bring about metabolic disorders in the offspring at different stages of ontogeny. Up to date, no ways of preventive pharmacological correction of lipid and carbohydrate metabolism disorders developing in different periods of ontogeny in the children born to mothers with this pregnancy complication, have been developed.The aim of the experiment was to study the effect of the gamma-aminobutyric acid derivative succicard (22 mg/kg) and its reference drug pantogam (50 mg) administered per os in the course of treatment in puberty (from 40 to 70 days after birth), on the parameters of lipid and carbohydrate metabolism in the offspring of the rats with experimental preeclampsia, in different periods of ontogeny.Materials and methods. To assess the activity of lipid and carbohydrate metabolism in the offspring, an oral glucose tolerance test was performed at 40 days, 3, 6, 12 and 18 months of age. The level of glycosylated hemoglobin was measured at the age of 6, 12, and 18 months, and the concentrations of total cholesterol, high-density lipoprotein cholesterol and triglycerides were tested at 40 days, 3, 6, 12, and 18 months of age.Results. The offspring of the rats with experimental preeclampsia, were found out to have lipid and carbohydrate metabolism disturbances during early (40 days and 3 months of age) and late (6, 12, and 18 months of age) ontogeny. In comparison with the offspring of healthy females, these disturbances were manifested by significantly higher levels of glucose revealed during the oral glucose tolerance test, by high glycosylated hemoglobin in males, and with elevated concentration of total cholesterol and triglycerides and a low level of high-density lipoprotein cholesterol in the negative control rats. Both the gamma-aminobutyric acid derivative succicard and its reference drug pantogam, reduced the negative effect of experimental preeclampsia on lipid and carbohydrate metabolism in the offspring in late ontogeny (6, 12 and 18 months of age). The effectiveness of succicard was either higher or comparable with pantogam.Conclusion. Thus, the negative impact manifestations of experimental preeclampsia on lipid and carbohydrate metabolism, are revealed in the offspring in early (40 days and 3 months) and late (6, 12 and 18 months of age) ontogeny. The gamma-aminobutyric acid derivative succicard reduces the negative effect of experimental preeclampsia. Based on this finding, the drug implies the possibility of the development of a safe and highly effective medicine for preventive correction of lipid and carbohydrate metabolism disorders in the children born to mothers with preeclampsia.

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“…While few studies have linked NDN to pregnancy complications, the literature does support the involvement of MEST aberrations in various pregnancy-related outcomes, including in vitro fertilization (IVF)/intracytoplasmic sperm injections (ICSIs) [ 43 ], viral load [ 44 ], gestational diabetes [ 45 ], and preeclampsia [ 46 ]. Interestingly, fetal growth restriction is among the most commonly reported outcomes linked to deviations in MEST activity [ 44 , 47 , 48 , 49 , 50 ], likely at least partially attributable to the purported role of MEST in placental angiogenesis and implantation [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

“…In studies where placental MEST gene expression levels were assessed [ 44 , 47 , 48 ], expression was generally downregulated, consistent with our findings in the current study. One study evaluated aberrations in MEST cord blood methylation levels in relation to preeclampsia and reported upregulated methylation in cases compared to controls [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Differences in Placental Imprinted Gene Expression across Preeclamptic and Non-Preeclamptic Pregnancies

Deyssenroth

Escudero

et al. 2020

Genes

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Preeclampsia is a multi-systemic syndrome that presents in approximately 5% of pregnancies worldwide and is associated with a range of subsequent postpartum and postnatal outcomes, including fetal growth restriction. As the placenta plays a critical role in the development of preeclampsia, surveying genomic features of the placenta, including expression of imprinted genes, may reveal molecular markers that can further refine subtypes to aid targeted disease management. In this study, we conducted a comprehensive survey of placental imprinted gene expression across early and late onset preeclampsia cases and preterm and term normotensive controls. Placentas were collected at delivery from women recruited at the Magee-Womens Hospital prenatal clinics, and expression levels were profiled across 109 imprinted genes. We observed downregulation of placental Mesoderm-specific transcript (MEST) and Necdin (NDN) gene expression levels (false discovery rate (FDR) < 0.05) among early onset preeclampsia cases compared to preterm controls. No differences in placental imprinted gene expression were observed between late onset preeclampsia cases and term controls. While few studies have linked NDN to pregnancy complications, reductions in MEST expression levels, as observed in our study, are consistently reported in the literature in relation to various pregnancy complications, including fetal growth restriction, suggesting a potential role for placental MEST expression as a biosensor of an adverse in utero environment.

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Alteration in methylation level at differential methylated regions of MEST and DLK1 in fetus of preeclampsia

Abstract: DMR: Differentially Methylated Region; MEST: Mesoderm Specific Transcript.

Cited by 9 publications

References 53 publications

Identification and characterization of methylation-mediated transcriptional dysregulation dictate methylation roles in preeclampsia

Identification and characterization of methylation-mediated transcriptional dysregulation dictate methylation roles in preeclampsia

Effect of the Gaba Derivative Succicard on the Lipid and Carbohydrate Metabolism in the Offspring of Rats With Experimental Preeclampsia in Early and Late Ontogeny

Differences in Placental Imprinted Gene Expression across Preeclamptic and Non-Preeclamptic Pregnancies

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