Dysregulation of Placental miRNA in Maternal Obesity Is Associated With Pre- and Postnatal Growth

Carreras‐Badosa, Gemma; Bonmatí, Alexandra; Ortega, Francisco; Mercader, Josep M.; Guindo-Martínez, Marta; Torrents, David; Prats‐Puig, Anna; Martínez-Calcerrada, Jose-María; Zegher, Francis de; Ibáñez, Lourdes; Fernández‐Real, José‐Manuel; López‐Bermejo, Abel; Bassols, Judit

doi:10.1210/jc.2017-00089

Cited by 62 publications

(51 citation statements)

References 39 publications

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“…Therefore, early life exposure of offspring to environmental stimuli, including altered nutrition during critical periods of development, can program alterations in organogenesis, tissue development and metabolism, predisposing offspring to obesity, metabolic and cardiovascular disorders in later life (Segovia, ; Carreras‐Badosa et al . ). In particular, the increasing prevalence of maternal obesity (MO) and excess maternal weight gain has been associated with additional risk of obesity in offspring (Nathanielsz et al .…”

Section: Introductionmentioning

confidence: 97%

Primate fetal hepatic responses to maternal obesity: epigenetic signalling pathways and lipid accumulation

Puppala

Glenn

et al. 2018

The Journal of Physiology

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Maternal obesity (MO) increases offspring cardiometabolic disease risk. Altered fetal liver development in response to the challenge of MO has metabolic consequences underlying adverse offspring life-course health outcomes. Little is known about the molecular pathways and potential epigenetic changes regulating primate fetal liver responses to MO. We hypothesized that MO would induce fetal baboon liver epigenetic changes resulting in dysregulation of key metabolic pathways that impact lipid metabolism. MO was induced prior to pregnancy by a high-fat, high-fructose diet. Unbiased gene and microRNA (small RNA Seq) abundance analyses were performed on fetal baboon livers at 0.9 gestation and subjected to pathway analyses to identify fetal liver molecular responses to MO. Fetal baboon liver lipid and glycogen content were quantified by the Computer Assisted Stereology Toolbox. In response to MO, fetal livers revealed dysregulation of TCA cycle, proteasome, oxidative phosphorylation, glycolysis and Wnt/β-catenin signalling pathways together with marked lipid accumulation supporting our hypothesis that multiple pathway dysregulation detrimentally impacts lipid management. This is the first study of MO programming of the non-human primate fetal liver using unbiased transcriptome analysis to detect changes in hepatic gene expression levels and identify potential microRNA epigenetic regulators of metabolic disruption.

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Section: Introductionmentioning

confidence: 97%

Primate fetal hepatic responses to maternal obesity: epigenetic signalling pathways and lipid accumulation

Puppala

Glenn

et al. 2018

The Journal of Physiology

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“…miR-181a and miR-221 are considered mitomiR that are implicated in mitochondrial and metabolic responses, because they have close interrelation with regulating proteins, transcription factors and signalling molecules in inflammation, apoptosis, metabolism, signal transduction and cell proliferation (18). In addition, miR-181 has been reported as a specific placental miRNA in maternal obesity and has an important role on the growth of the offspring because of its regulatory effects on cell proliferation and insulin signalling (19). Cell-free circulating miR-221 concentrations have been reported in association to obesity and type 2 diabetes in several studies supporting its significant role in these disorders (20).…”

Section: Introductionmentioning

confidence: 99%

Differential expression profiles of circulating microRNAs in newborns associated to maternal pregestational overweight and obesity

et al. 2017

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“…MiR‐410 could induce human embryonic stem cells to differentiate into islet endoderm, promote β‐cell proliferation, increase insulin secretion and greatly improve glucose metabolism in mice with GDM by direct targeting lactate dehydrogenase A 55 . In addition, miR‐185 has also been involved in the insulin signaling pathway 56 . MiRNAs are important post‐transcriptional regulators of gene expression and key elements in ceRNAs by direct base pairing to target genes to regulate mRNA expression, and influence the occurrence and development of diseases 17,31 .…”

Section: Discussionmentioning

confidence: 99%

Whole transcriptome expression profiles in placenta samples from women with gestational diabetes mellitus

Tang

2020

J of Diabetes Invest

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Aims/Introduction Non‐coding ribonucleic acids (ncRNAs) have recently been shown to be involved in various biological processes. However, most of these ncRNAs are of unknown function or without annotation. This study first investigated the whole transcriptome profiles of placentas to identify the potential functions that ncRNAs exerted in gestational diabetes mellitus (GDM). Materials and Methods Six placenta samples from healthy pregnant women (n = 3) and GDM (n = 3) were collected to analyze the whole transcriptome profiles by high‐throughput sequencing. Differentially expressed ncRNAs were further validated by quantitative real‐time polymerase chain reaction on an independent set of normal (n = 20) and GDM (n = 20) placenta samples. Results A total of 2,817 microRNAs (miRNAs), 23,339 long non‐coding RNAs (lncRNAs) and 9,513 circular RNAs (circRNAs) were identified. There were 290 differentially expressed ncRNAs in GDM placentas compared with the placentas of healthy pregnant women. Two miRNAs, 86 lncRNAs and 55 circRNAs were upregulated, while two miRNAs, 86 lncRNAs and 59 circRNAs were downregulated in GDM. The expression of the selected ncRNAs, which were further validated by quantitative real‐time polymerase chain reaction, was consistent with the sequencing results. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the major targets of these ncRNAs were associated with insulin resistance, and abnormal glucose and lipid metabolism. A GDM‐related competing endogenous RNA network suggested the interactions between lncRNAs, circRNAs, messenger RNAs and miRNAs. Conclusions The whole transcriptome profiles significantly differed in GDM placentas compared with the placentas of healthy pregnant women, which might be valuable for detecting novel ncRNAs, and providing new research insights into exploring the pathogenic mechanisms of GDM.

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Dysregulation of Placental miRNA in Maternal Obesity Is Associated With Pre- and Postnatal Growth

Abstract: We identified a specific placental miRNA profile in maternal obesity. Placental miRNAs dysregulated in maternal obesity may be involved in mediation of growth-promoting effects of maternal obesity on offspring and could be used as early markers of prenatal and postnatal growth.

Cited by 62 publications

References 39 publications

Primate fetal hepatic responses to maternal obesity: epigenetic signalling pathways and lipid accumulation

Primate fetal hepatic responses to maternal obesity: epigenetic signalling pathways and lipid accumulation

Differential expression profiles of circulating microRNAs in newborns associated to maternal pregestational overweight and obesity

Whole transcriptome expression profiles in placenta samples from women with gestational diabetes mellitus

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