Expression and regulation of metallothioneins in myometrium and fetal membranes

Lappas, Martha

doi:10.1111/aji.13040

Cited by 7 publications

(4 citation statements)

References 53 publications

(81 reference statements)

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“…Thus, the reduced availability of MT1M would be expected to enhance oxidative stress by altered regulation of superoxide radicals, as well as by effects on zinc metabolism [ 37 ]. Additionally, previous research also showed that the expression of MT1M was regulated by pro-inflammatory cytokines, indicating MT1M might participate in the inflammation process as well [ 38 ]. The relationship between MT1M and HCM has not been reported before; therefore, in-depth research is needed to reveal the underlying mechanism of MT1M on HCM.…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Diagnostic Biomarkers and Biological Pathways in Hypertrophic Cardiomyopathy Based on Bioinformatics Analysis

Huang

2022

Genes

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Hypertrophic cardiomyopathy (HCM) is a genetic heterogeneous disorder and the main cause of sudden cardiac death in adolescents and young adults. This study was aimed at identifying potential diagnostic biomarkers and biological pathways to help to diagnose and treat HCM through bioinformatics analysis. We selected the GSE36961 dataset from the Gene Expression Omnibus (GEO) database and identified 893 differentially expressed genes (DEGs). Subsequently, 12 modules were generated through weighted gene coexpression network analysis (WGCNA), and the turquoise module showed the highest negative correlation with HCM (cor = −0.9, p-value = 4 × 10−52). With the filtering standard gene significance (GS) < −0.7 and module membership (MM) > 0.9, 19 genes were then selected to establish the least absolute shrinkage and selection operator (LASSO) model, and LYVE1, MAFB, and MT1M were finally identified as key genes. The expression levels of these genes were additionally verified in the GSE130036 dataset. Gene Set Enrichment Analysis (GSEA) showed oxidative phosphorylation, tumor necrosis factor alpha-nuclear factor-κB (TNFα-NFκB), interferon-gamma (IFNγ) response, and inflammatory response were four pathways possibly related to HCM. In conclusion, LYVE1, MAFB, and MT1M were potential biomarkers of HCM, and oxidative stress, immune response as well as inflammatory response were likely to be associated with the pathogenesis of HCM.

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Section: Discussionmentioning

confidence: 99%

Identification of Potential Diagnostic Biomarkers and Biological Pathways in Hypertrophic Cardiomyopathy Based on Bioinformatics Analysis

Huang

2022

Genes

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“…A small study by Lappas et al. demonstrated that MT1‐4 was upregulated in intrauterine tissues in women with PTD complicated by bacterial infection 85 . It has also been shown that MT1A is expressed in the foetal membranes in women delivering preterm 86 and MT1A was higher in membranes close to the rupture site compared with more distant sites in women with spontaneous rupture of the membranes at term 87 .…”

Section: Discussionmentioning

confidence: 99%

Microbial and human transcriptome in vaginal fluid at midgestation: Association with spontaneous preterm delivery

Wikström

Abrahamsson

Bengtsson‐Palme

et al. 2022

Clinical & Translational Med

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Background Intrauterine infection and inflammation caused by microbial transfer from the vagina are believed to be important factors causing spontaneous preterm delivery (PTD). Multiple studies have examined the relationship between the cervicovaginal microbiome and spontaneous PTD with divergent results. Most studies have applied a DNA‐based assessment, providing information on the microbial composition but not transcriptional activity. A transcriptomic approach was applied to investigate differences in the active vaginal microbiome and human transcriptome at midgestation between women delivering spontaneously preterm versus those delivering at term. Methods Vaginal swabs were collected in women with a singleton pregnancy at 18 + 0 to 20 + 6 gestational weeks. For each case of spontaneous PTD (delivery <37 + 0 weeks) two term controls were randomized (39 + 0 to 40 + 6 weeks). Vaginal specimens were subject to sequencing of both human and microbial RNA. Microbial reads were taxonomically classified using Kraken2 and RefSeq as a reference. Statistical analyses were performed using DESeq2. GSEA and HUMAnN3 were used for pathway analyses. Results We found 17 human genes to be differentially expressed (false discovery rate, FDR < 0.05) in the preterm group (n = 48) compared to the term group (n = 96). Gene expression of kallikrein‐2 (KLK2), KLK3 and four isoforms of metallothioneins 1 (MT1s) was higher in the preterm group (FDR < 0.05). We found 11 individual bacterial species to be differentially expressed (FDR < 0.05), most with a low occurrence. No statistically significant differences in bacterial load, diversity or microbial community state types were found between the groups. Conclusions In our mainly white population, primarily bacterial species of low occurrence were differentially expressed at midgestation in women who delivered preterm versus at term. However, the expression of specific human transcripts including KLK2, KLK3 and several isoforms of MT1s was higher in preterm cases. This is of interest, because these genes may be involved in critical inflammatory pathways associated with spontaneous PTD.

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“…CHAC2 has a pivotal role in the neutralization of reactive oxygen species, being necessary for the maintenance of human embryonic stem cell self-renewal [ 32 ]. MT1M is critical for regulating oxidative stress, inflammation and hormone signaling in term and preterm labor [ 33 ]. SOSTDC1 , was found expressed in the uterine glandular epithelial cells of the receptive rat endometrium, and thus, may be involved in the onset of endometrial receptivity [ 34 ], while RRM2 expression was downregulated in the RIF endometrium, compared to fertile controls [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of adenomyosis eutopic endometrium reveals molecular mechanisms involved in adenomyosis-related implantation failure and pregnancy disorders

Juárez-Barber,

Corachán,

Carbajo-García

et al. 2024

Reprod Biol Endocrinol

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Background Women with adenomyosis are characterized by having defective decidualization, impaired endometrial receptivity and/or embryo-maternal communication, and implantation failure. However, the molecular mechanisms underlying adenomyosis-related infertility remain unknown, mainly because of the restricted accessibility and the difficult preservation of endometrial tissue in vitro. We have recently shown that adenomyosis patient-derived endometrial organoids, maintain disease-specific features while differentiated into mid-secretory and gestational endometrial phase, overcoming these research barriers and providing a robust platform to study adenomyosis pathogenesis and the associated molecular dysregulation related to implantation and pregnancy disorders. For this reason, we aim to characterize the dysregulated mechanisms in the mid-secretory and gestational endometrium of patients with adenomyosis by RNA-sequencing. Methods Endometrial organoids were derived from endometrial biopsies collected in the proliferative phase of women with adenomyosis (ADENO) or healthy oocyte donors (CONTROL) (n = 15/group) and differentiated into mid-secretory (-SECorg) and gestational (-GESTorg) phases in vitro. Following RNA-sequencing, the significantly differentially expressed genes (DEGs) (FDR < 0.05) were identified and selected for subsequent functional enrichment analysis and QIAGEN Ingenuity Pathway Analysis (IPA). Statistical differences in gene expression were evaluated with the Student’s t-test or Wilcoxon test. Results We identified 1,430 DEGs in ADENO-SECorg and 1,999 DEGs in ADENO-GESTorg. In ADENO-SECorg, upregulated genes included OLFM1, FXYD5, and RUNX2, which are involved in impaired endometrial receptivity and implantation failure, while downregulated genes included RRM2, SOSTDC1, and CHAC2 implicated in recurrent implantation failure. In ADENO-GESTorg, upregulated CXCL14 and CYP24A1 and downregulated PGR were related to pregnancy loss. IPA predicted a significant inhibition of ID1 signaling, histamine degradation, and activation of HMGB1 and Senescence pathways, which are related to implantation failure. Alternatively, IPA predicted an inhibition of D-myo-inositol biosynthesis and VEGF signaling, and upregulation of Rho pathway, which are related to pregnancy loss and preeclampsia. Conclusions Identifying dysregulated molecular mechanisms in mid-secretory and gestational endometrium of adenomyosis women contributes to the understanding of adenomyosis-related implantation failure and/or pregnancy disorders revealing potential therapeutic targets. Following experimental validation of our transcriptomic and in silico findings, our differentiated adenomyosis patient-derived organoids have the potential to provide a reliable platform for drug discovery, development, and personalized drug screening for affected patients.

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Expression and regulation of metallothioneins in myometrium and fetal membranes

Cited by 7 publications

References 53 publications

Identification of Potential Diagnostic Biomarkers and Biological Pathways in Hypertrophic Cardiomyopathy Based on Bioinformatics Analysis

Identification of Potential Diagnostic Biomarkers and Biological Pathways in Hypertrophic Cardiomyopathy Based on Bioinformatics Analysis

Microbial and human transcriptome in vaginal fluid at midgestation: Association with spontaneous preterm delivery

Transcriptome analysis of adenomyosis eutopic endometrium reveals molecular mechanisms involved in adenomyosis-related implantation failure and pregnancy disorders

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