Evidence map›Paper›PMID 41188995›Full record

ArticleGenome biology2025

ERV3-MLT1 provides cis-regulatory elements for human placental functioning and are commonly dysregulated in human-specific preeclampsia.

Rabia Anwar, Amit Pande, Manvendra Singh, Zhi Huang, Eve Hallett, Yiran Xie, Alexandra Gellhaus, Florian Herse, Olivia Nonn, Martin Gauster and 9 more

Abstract read
In one paragraph

Article in Genome biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Review
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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

19 authors.

Rabia Anwar *The Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany.
Amit Pande *The Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany.
Manvendra Singh *The Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany.
Zhi HuangThe Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany.
Eve HallettThe Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany.
Yiran XieDepartment of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Alexandra GellhausDepartment of Gynecology and Obstetrics, University Hospital Essen, Essen, Germany.
Florian HerseThe Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany.
Olivia NonnExperimental and Clinical Research Center, a joint cooperation between the Max Delbrück Center for Molecular Medicine and the Charité, Universitätsmedizin Berlin, 13125, Berlin, Germany.
Martin GausterDivision of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria.
Tamás RaskóThe Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany.
Matthias SelbachThe Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany.
Stefan VerlohrenDepartment of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Anne Cathrine StaffFaculty of Medicine, University of Oslo, Oslo, Norway.
Ralf DechendThe Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany.
Ulrich PecksMaternal Health and Midwifery, Ludwig Maximillians University, Würzburg, Germany.
Sandra M BloisDepartment of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Laurence D HurstThe Milner Centre for Evolution, Department of Life Sciences, University of Bath, Bath, BA2 7AY, UK. bssldh@bath.ac.uk.
Zsuzsanna IzsvákThe Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Robert-Rössle-Straße 10, 13125, Berlin, Germany. zizsvak@mdc-berlin.de.

Funding

Deutsche Forschungsgemeinschaft GE2223/2-1, GE2223/6-1Deutsche Forschungsgemeinschaft HE 6249/5-1Heisenberg Program BL1115/3-1, BL1115/7-1, and BL1115/11-1
6 · The paper itself

Abstract

backgroundOwing to their transcription factor binding sites, endogenous retroviruses (ERVs) can act as cis-regulatory-elements (CREs). By invading genomes in waves, ERVs offer a substrate for lineage-specific adaptations but also, when dysregulated, for lineage-specific disorders. Their role as CREs in rapid placental evolution, and in the human-specific placental disorder preeclampsia, may thus provide a paradigmatic exemplar. Here then we systematically identify ERV-derived CREs controlling human placental gene expression with dysregulation in preeclampsia.

resultsWe identify 87 ERV-derived CREs located upstream of genes expressed in the placenta. A subset of nine, all belonging to the ERV3-MLT1/2 families and dating to the mouse-human common ancestor, are consistently dysregulated in trophoblasts from preeclampsia samples. Of the nine ERV3-MLT1-linked genes dysregulated in preeclampsia, five are novel candidates, while four were previously associated with preeclampsia, though their ERV-based regulation was not recognized. Focusing on EPS8L1, we predict enhancer activity of upstream MLT1(G1) and validate using reporter assay and genome editing. This vertebrate-specific gene is expressed in progenitor cytotrophoblasts and syncytiotrophoblasts and is overexpressed in preeclampsia, correlating with preeclampsia biomarkers and is not elevated in related pregnancy disorders. A soluble form of EPS8L1 is detectable in maternal plasma as early as between 24 weeks of gestation. EPS8L1 knockout in trophoblast in vitro is lethal, and its overexpression alters trophoblast behaviors characteristic of preeclampsia.

conclusionsWe conclude that ERV3-MLT1functions as a trophoblast-specific CRE for several human genes and may be dysregulated in preeclampsia. As EPS8L1 has a form in maternal circulation, it may have utility in diagnostics.

Indexed as

Endogenous RetrovirusesPlacentaPre-EclampsiaAnimalsFemaleGene Expression RegulationHumansPregnancyTrophoblasts

Identifiers

PMID41188995
PMCPMC12587658

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