Evidence map›Paper›PMID 25697377›Full record

ArticleMolecular human reproduction2015

Genome-wide DNA methylation identifies trophoblast invasion-related genes: Claudin-4 and Fucosyltransferase IV control mobility via altering matrix metalloproteinase activity.

Yuxiang Hu, John D Blair, Ryan K C Yuen, Wendy P Robinson, Peter von Dadelszen

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular human reproduction, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.7field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Trophoblast adaptation to hypoxia: balance and dysfunction.Cell communication and signaling : CCS · 2025
    Review
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  4. Article
  5. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Yuxiang HuDepartment of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC, Canada Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
John D BlairChild and Family Research Institute, University of British Columbia, Vancouver, BC, Canada Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
Ryan K C YuenGenetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Wendy P RobinsonChild and Family Research Institute, University of British Columbia, Vancouver, BC, Canada Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
Peter von DadelszenDepartment of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC, Canada Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada pvd@cw.bc.ca.
Child and Family Research Institute · CAUniversity of British Columbia · CAHospital for Sick Children · CA

Funding

Canadian Institutes of Health Research 49520
6 · The paper itself

Abstract

Previously we showed that extravillous cytotrophoblast (EVT) outgrowth and migration on a collagen gel explant model were affected by exposure to decidual natural killer cells (dNK). This study investigates the molecular causes behind this phenomenon. Genome wide DNA methylation of exposed and unexposed EVT was assessed using the Illumina Infinium HumanMethylation450 BeadChip array (450 K array). We identified 444 differentially methylated CpG loci in dNK-treated EVT compared with medium control (P < 0.05). The genes associated with these loci had critical biological roles in cellular development, cellular growth and proliferation, cell signaling, cellular assembly and organization by Ingenuity Pathway Analysis (IPA). Furthermore, 23 mobility-related genes were identified by IPA from dNK-treated EVT. Among these genes, CLDN4 (encoding claudin-4) and FUT4 (encoding fucosyltransferase IV) were chosen for follow-up studies because of their biological relevance from research on tumor cells. The results showed that the mRNA and protein expressions of both CLDN4 and FUT4 in dNK-treated EVT were significantly reduced compared with control (P < 0.01 for both CLDN4 and FUT4 mRNA expression; P < 0.001 for CLDN4 and P < 0.01 for FUT4 protein expression), and were inversely correlated with DNA methylation. Knocking down CLDN4 and FUT4 by small interfering RNA reduced trophoblast invasion, possibly through the altered matrix metalloproteinase (MMP)-2 and/or MMP-9 expression and activity. Taken together, dNK alter EVT mobility at least partially in association with an alteration of DNA methylation profile. Hypermethylation of CLDN4 and FUT4 reduces protein expression. CLDN4 and FUT4 are representative genes that participate in modulating trophoblast mobility.

Indexed as

DNA MethylationPlacentationCell LineCell MovementCells, CulturedClaudin-4Coculture TechniquesDeciduaFemaleFucosyltransferasesGene Expression Regulation, DevelopmentalHumansKiller Cells, NaturalMatrix Metalloproteinase 2Matrix Metalloproteinase 9Pregnancy3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferaseClaudin-4CLDN4 protein, humanFucosyltransferasesMatrix Metalloproteinase 2Matrix Metalloproteinase 9MMP2 protein, humanMMP9 protein, humanClaudin-4decidual natural killer cellsDNA methylationextravillous cytotrophoblastFucosyltransferase IV

Identifiers

PMID25697377
PMCPMC4407676
OpenAlexW2121130537

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.