Evidence map›Paper›PMID 30808910›Full record

ArticleScientific reports2019

Trophoblast-Specific Expression of Hif-1α Results in Preeclampsia-Like Symptoms and Fetal Growth Restriction.

Renee E Albers, Melissa R Kaufman, Bryony V Natale, Chanel Keoni, Kashmira Kulkarni-Datar, Sarah Min, Clintoria R Williams, David R C Natale, Thomas L Brown

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 1 pooled it
9.4field-weighted citation impact, top 2% 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

67 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.

  1. Pooled it
  2. Review
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  7. Article
  8. Trophoblast adaptation to hypoxia: balance and dysfunction.Cell communication and signaling : CCS · 2025
    Review
  9. Review
  10. Article
  11. Article
  12. The uteroplacental circulation at high altitude: adaptation and maladaptation.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025
    Review
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  14. Article
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7 more citing papers are in PubMed but not listed here.

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

9 authors at 2 institutions in 1 country.

Renee E AlbersDepartment of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine, Dayton, Ohio, 45435, USA.
Melissa R KaufmanDepartment of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine, Dayton, Ohio, 45435, USA.
Bryony V NataleDepartment of Reproductive Medicine, University of California-San Diego, San Diego, California, 92093, USA.
Chanel KeoniDepartment of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine, Dayton, Ohio, 45435, USA.
Kashmira Kulkarni-DatarDepartment of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine, Dayton, Ohio, 45435, USA.
Sarah MinDepartment of Reproductive Medicine, University of California-San Diego, San Diego, California, 92093, USA.
Clintoria R WilliamsDepartment of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine, Dayton, Ohio, 45435, USA.
David R C NataleDepartment of Reproductive Medicine, University of California-San Diego, San Diego, California, 92093, USA. dnatale@ucsd.edu.ORCID 0000-0001-8365-455X
Thomas L BrownDepartment of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine, Dayton, Ohio, 45435, USA. thomas.L.brown@wright.edu.
Wright State University · USUniversity of California San Diego · US

Funding

HIF-1 Alpha Regulation of Trophoblast Differentiation in VivoR01HD059969 · NICHD · WRIGHT STATE UNIVERSITY · PI BROWN, THOMAS L · 2011 to 2015
$1.6M
CIHR 201203MOP-275374-CIA-CBBA-109624NICHD NIH HHS R01 HD059969
6 · The paper itself

Abstract

The placenta is an essential organ that is formed during pregnancy and its proper development is critical for embryonic survival. While several animal models have been shown to exhibit some of the pathological effects present in human preeclampsia, these models often do not represent the physiological aspects that have been identified. Hypoxia-inducible factor 1 alpha (Hif-1α) is a necessary component of the cellular oxygen-sensing machinery and has been implicated as a major regulator of trophoblast differentiation. Elevated levels of Hif-1α in the human placenta have been linked to the development of pregnancy-associated disorders, such as preeclampsia and fetal growth restriction. As oxygen regulation is a critical determinant for placentogenesis, we determined the effects of constitutively active Hif-1α, specifically in trophoblasts, on mouse placental development in vivo. Our research indicates that prolonged expression of trophoblast-specific Hif-1α leads to a significant decrease in fetal birth weight. In addition, we noted significant physiological alterations in placental differentiation that included reduced branching morphogenesis, alterations in maternal and fetal blood spaces, and failure to remodel the maternal spiral arteries. These placental alterations resulted in subsequent maternal hypertension with parturitional resolution and maternal kidney glomeruloendotheliosis with accompanying proteinuria, classic hallmarks of preeclampsia. Our findings identify Hif-1α as a critical molecular mediator of placental development and indicate that prolonged expression of Hif-1α, explicitly in placental trophoblasts causes maternal pathology and establishes a mouse model that significantly recapitulates the physiological and pathophysiological characteristics of preeclampsia with fetal growth restriction.

Indexed as

PlacentationAnimalsFemaleFetal Growth RetardationHypoxia-Inducible Factor 1, alpha SubunitKidneyMaleMiceMice, Inbred C57BLMice, Inbred ICRPlacentaPre-EclampsiaPregnancyTrophoblastsHif1a protein, mouseHypoxia-Inducible Factor 1, alpha Subunit

Identifiers

PMID30808910
PMCPMC6391498
OpenAlexW2922230818

What OpenQuestion holds

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LicenceCC BY
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.