The Role of Cellular Stress in Intrauterine Growth Restriction and Postnatal Dysmetabolism

Oke, Shelby L; Hardy, Daniel B.

doi:10.20944/preprints202105.0730.v1

Cited by 5 publications

(1 citation statement)

References 113 publications

(147 reference statements)

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“…Impaired immune responses may also lead to metabolic diseases in individuals with FGR [12]. A high-throughput RNA sequencing analysis based on the FGR sheep model showed that the transcriptome responsible for B cell dysfunction was involved in immune response, WNT signal 4 transduction, and adaptive stress response pathways [13].…”

Section: Introductionmentioning

confidence: 99%

Integrative analysis of the immune-related ceRNA network in fetal growth restriction based on weighted gene co-expression network analysis

Zhao

2022

Arch Gynecol Obstet

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Immune disorders lead to placental dysfunction and fetal growth restriction (FGR), but current research on the immune regulation mechanisms of FGR is insufficient. Therefore, this study aimed to construct an immune-related competing endogenous RNA (ceRNA) network to predict FGR onset risk. Methods: Based on microarray data from the GEO database, CIBERSORT was used to analyze immune cell infiltration. Weighted gene co-expression network analysis (WGCNA) was used to screen immune-related module genes with differential expression (DE) in FGR. A ceRNA network was constructed by integrating long non-coding RNA (lncRNA)-mRNA co-expression relations, lncRNA-microRNA (miRNA) relations, and miRNA-mRNA negative regulatory relations. The diagnostic values of key genes in the network and their relationships with immune cell infiltration were 2 further validated. Results: By comparing FGR and normal samples, 442 DE mRNAs, 57 DE miRNAs, and 241 DE lncRNAs were obtained. Furthermore, four types of immune cells exhibited significantly different infiltration levels. WGCNA revealed 236 immune-related DE mRNAs that were involved in hormone secretion and immune cell differentiation. We then constructed a ceRNA network comprising 16 lncRNAs, 16 miRNAs, and 21 mRNAs through co-expression analysis and miRNA prediction.Receiver operating characteristic curves confirmed the superior predictive performance of key genes in the network for FGR. The validation dataset confirmed the increased infiltration of M1 macrophages in FGR samples and their positive correlations with NEURL1 and ODF3B expression. Conclusion:We constructed an immune-related ceRNA regulatory network wherein key genes are positively correlated with M1 macrophage infiltration and can be used for FGR diagnosis.

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Section: Introductionmentioning

confidence: 99%

Integrative analysis of the immune-related ceRNA network in fetal growth restriction based on weighted gene co-expression network analysis

Zhao

2022

Arch Gynecol Obstet

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The Impact of Oxidative Stress of Environmental Origin on the Onset of Placental Diseases

2022

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Oxidative stress (OS) plays a pivotal role in placental development; however, abnormal loads in oxidative stress molecules may overwhelm the placental defense mechanisms and cause pathological situations. The environment in which the mother evolves triggers an exposure of the placental tissue to chemical, physical, and biological agents of OS, with potential pathological consequences. Here we shortly review the physiological and developmental functions of OS in the placenta, and present a series of environmental pollutants inducing placental oxidative stress, for which some insights regarding the underlying mechanisms have been proposed, leading to a recapitulation of the noxious effects of OS of environmental origin upon the human placenta.

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Stress-Induced Premature Senescence Related to Oxidative Stress in the Developmental Programming of Nonalcoholic Fatty Liver Disease in a Rat Model of Intrauterine Growth Restriction

et al. 2022

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Metabolic syndrome (MetS) refers to cardiometabolic risk factors, such as visceral obesity, dyslipidemia, hyperglycemia/insulin resistance, arterial hypertension and non-alcoholic fatty liver disease (NAFLD). Individuals born after intrauterine growth restriction (IUGR) are particularly at risk of developing metabolic/hepatic disorders later in life. Oxidative stress and cellular senescence have been associated with MetS and are observed in infants born following IUGR. However, whether these mechanisms could be particularly associated with the development of NAFLD in these individuals is still unknown. IUGR was induced in rats by a maternal low-protein diet during gestation versus. a control (CTRL) diet. In six-month-old offspring, we observed an increased visceral fat mass, glucose intolerance, and hepatic alterations (increased transaminase levels, triglyceride and neutral lipid deposit) in male rats with induced IUGR compared with the CTRL males; no differences were found in females. In IUGR male livers, we identified some markers of stress-induced premature senescence (SIPS) (lipofuscin deposit, increased protein expression of p21WAF, p16INK4a and Acp53, but decreased pRb/Rb ratio, foxo-1 and sirtuin-1 protein and mRNA expression) associated with oxidative stress (higher superoxide anion levels, DNA damages, decreased Cu/Zn SOD, increased catalase protein expression, increased nfe2 and decreased keap1 mRNA expression). Impaired lipogenesis pathways (decreased pAMPK/AMPK ratio, increased pAKT/AKT ratio, SREBP1 and PPARγ protein expression) were also observed in IUGR male livers. At birth, no differences were observed in liver histology, markers of SIPS and oxidative stress between CTRL and IUGR males. These data demonstrate that the livers of IUGR males at adulthood display SIPS and impaired liver structure and function related to oxidative stress and allow the identification of specific therapeutic strategies to limit or prevent adverse consequences of IUGR, particularly metabolic and hepatic disorders.

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The Role of Cellular Stress in Intrauterine Growth Restriction and Postnatal Dysmetabolism

Cited by 5 publications

References 113 publications

Integrative analysis of the immune-related ceRNA network in fetal growth restriction based on weighted gene co-expression network analysis

Integrative analysis of the immune-related ceRNA network in fetal growth restriction based on weighted gene co-expression network analysis

The Impact of Oxidative Stress of Environmental Origin on the Onset of Placental Diseases

Stress-Induced Premature Senescence Related to Oxidative Stress in the Developmental Programming of Nonalcoholic Fatty Liver Disease in a Rat Model of Intrauterine Growth Restriction

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