Evidence map›Paper›PMID 25266889›Full record

ArticlePlacenta2014

Evolutionary origins of the placental expression of chromosome 19 cluster galectins and their complex dysregulation in preeclampsia.

N G Than, R Romero, Y Xu, O Erez, Z Xu, G Bhatti, R Leavitt, T H Chung, H El-Azzamy, C LaJeunesse and 12 more

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In one paragraph

Article in Placenta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
6.4field-weighted citation impact, top 3% 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

57 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.

  1. Pooled it
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  9. Trophoblast Fusion in Hypertensive Disorders of Pregnancy and Preeclampsia.International journal of molecular sciences · 2025
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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

22 authors at 6 institutions in 4 countries.

N G ThanPerinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, and Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; Maternity Private Department, Kutvolgyi Clinical Block, Semmelweis University, Budapest, Hungary; Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary. Electronic address: nthan@med.wayne.edu.
R RomeroPerinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, and Detroit, MI, USA. Electronic address: romeror@mail.nih.gov.
Y XuPerinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, and Detroit, MI, USA.
O ErezDepartment of Obstetrics and Gynecology, Ben-Gurion University, Beer-Sheva, Israel.
Z XuPerinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, and Detroit, MI, USA.
G BhattiPerinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, and Detroit, MI, USA.
R LeavittZymo Research Corporation, Irvine, CA, USA.
T H ChungZymo Research Corporation, Irvine, CA, USA.
H El-AzzamyPerinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, and Detroit, MI, USA.
C LaJeunessePerinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, and Detroit, MI, USA.
B WangPerinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, and Detroit, MI, USA.
A BaloghPerinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, and Detroit, MI, USA; Department of Immunology, Eotvos Lorand University, Budapest, Hungary.
G SzalaiPerinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, and Detroit, MI, USA.
S LandCenter for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA.
Z DongPerinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, and Detroit, MI, USA.
S S HassanPerinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, and Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
T ChaiworapongsaPerinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, and Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
M KrispinZymo Research Corporation, Irvine, CA, USA.
C J KimPerinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, and Detroit, MI, USA; Department of Pathology, Wayne State University School of Medicine, Detroit, MI, USA.
A L TarcaPerinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD, and Detroit, MI, USA; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA.
Z PappMaternity Private Department, Kutvolgyi Clinical Block, Semmelweis University, Budapest, Hungary.
H BohnBehringwerke AG, Marburg/Lahn, Germany.
Eunice Kennedy Shriver National Institute of Child Health and Human Development · USNational Institutes of Health · USBehringwerke (Germany) · DEBen-Gurion University of the Negev · ILSemmelweis University · HUWayne State University · US

Funding

The Role Of Subclinical Infection And Cytokines In Preterm ParturitionZIAHD002400 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI ROMERO, ROBERTO · 2009 to 2025
$254.4M
Intramural NIH HHS ZIA HD002400NICHD NIH HHS HHSN275201300006C
6 · The paper itself

Abstract

introductionThe dysregulation of maternal-fetal immune tolerance is one of the proposed mechanisms leading to preeclampsia. Galectins are key regulator proteins of the immune response in vertebrates and maternal-fetal immune tolerance in eutherian mammals. Previously we found that three genes in a Chr19 cluster encoding for human placental galectin-13 (PP13), galectin-14 and galectin-16 emerged during primate evolution and may confer immune tolerance to the semi-allogeneic fetus. MATERIALS AND

methodsThis study involved various methodologies for gene and protein expression profiling, genomic DNA methylation analyses, functional assays on differentiating trophoblasts including gene silencing, luciferase reporter and methylation assays. These methods were applied on placental specimens, umbilical cord blood cells, primary trophoblasts and BeWo cells. Genomic DNA sequences were analyzed for transposable elements, transcription factor binding sites and evolutionary conservation. RESULTS AND DISCUSSION: The villous trophoblastic expression of Chr19 cluster galectin genes is developmentally regulated by DNA methylation and induced by key transcription factors of villous placental development during trophoblast fusion and differentiation. This latter mechanism arose via the co-option of binding sites for these transcription factors through promoter evolution and the insertion of an anthropoid-specific L1PREC2 transposable element into the 5' untranslated region of an ancestral gene followed by gene duplication events. Among placental Chr19 cluster galectin genes, the expression of LGALS13 and LGALS14 is down-regulated in preterm severe preeclampsia associated with SGA. We reveal that this phenomenon is partly originated from the dysregulated expression of key transcription factors controlling trophoblastic functions and galectin gene expression. In addition, the differential DNA methylation of these genes was also observed in preterm preeclampsia irrespective of SGA.

conclusionsThese findings reveal the evolutionary origins of the placental expression of Chr19 cluster galectins. The complex dysregulation of these genes in preeclampsia may alter immune tolerance mechanisms at the maternal-fetal interface.

Indexed as

Chromosomes, Human, Pair 19Evolution, Molecular5' Untranslated RegionsCell DifferentiationDown-RegulationEpigenesis, GeneticFemaleGalectinsHumansMultigene FamilyPre-EclampsiaPregnancyTranscription FactorsTrophoblasts5' Untranslated RegionsGalectinsTranscription FactorsALUAnthropoid primateAP2EpigenomeESRRGGATAGCM1LectinLINEPP13PregnancySyncytiotrophoblastTEF5

Identifiers

PMID25266889
PMCPMC4203431
OpenAlexW2009657056

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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.