Evidence map›Paper›PMID 34963058›Full record

ArticleDevelopmental cell2022

The imprinted Igf2-Igf2r axis is critical for matching placental microvasculature expansion to fetal growth.

Ionel Sandovici, Aikaterini Georgopoulou, Vicente Pérez-García, Antonia Hufnagel, Jorge López-Tello, Brian Y H Lam, Samira N Schiefer, Chelsea Gaudreau, Fátima Santos, Katharina Hoelle and 8 more

Open access · hybridAbstract read
In one paragraph

Article in Developmental cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 1 pooled it
12.6field-weighted citation impact, top 1% 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

74 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.

  1. Pooled it
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  10. H19 and IGF2 imprinting from embryogenesis to oncogenesis.Frontiers in cell and developmental biology · 2026
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  14. Genes & development · 2025
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  17. Methionine metabolism, functions, and application in swine.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025
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  20. DNA Methylation ofBiology · 2025
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14 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

18 authors at 5 institutions in 2 countries.

Ionel SandoviciDepartment of Obstetrics and Gynaecology and National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge CB2 0SW, UK; Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge CB2 0QQ, UK; Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK. Electronic address: is299@cam.ac.uk.
Aikaterini GeorgopoulouDepartment of Obstetrics and Gynaecology and National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge CB2 0SW, UK; Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
Vicente Pérez-GarcíaCentre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK; Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK; Centro de Investigación Príncipe Felipe, Eduardo Primo Yúfera, 46012 Valencia, Spain.
Antonia HufnagelDepartment of Obstetrics and Gynaecology and National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge CB2 0SW, UK.
Jorge López-TelloCentre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
Brian Y H LamWellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge CB2 0QQ, UK.
Samira N SchieferDepartment of Obstetrics and Gynaecology and National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge CB2 0SW, UK.
Chelsea GaudreauWellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge CB2 0QQ, UK.
Fátima SantosCentre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK; Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
Katharina HoelleDepartment of Obstetrics and Gynaecology and National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge CB2 0SW, UK.
Giles S H YeoWellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge CB2 0QQ, UK.
Keith BurlingWellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge CB2 0QQ, UK.
Moritz ReitererPhysiological Laboratory, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK; Center for Cancer Research and Cell Biology, Queen's University Belfast, Belfast BT9 7AE, UK.
Abigail L FowdenCentre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
Graham J BurtonCentre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
Cristina M BrancoPhysiological Laboratory, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK; Center for Cancer Research and Cell Biology, Queen's University Belfast, Belfast BT9 7AE, UK.
Amanda N Sferruzzi-PerriCentre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
Miguel ConstânciaDepartment of Obstetrics and Gynaecology and National Institute for Health Research Cambridge Biomedical Research Centre, University of Cambridge, Cambridge CB2 0SW, UK; Wellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, Cambridge CB2 0QQ, UK; Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK. Electronic address: jmasmc2@cam.ac.uk.
University of Cambridge · GBMedical Research Council · GBNational Institute for Health Research · GBQueen's University Belfast · GBWellcome/MRC Institute of Metabolic Science · GB

Funding

Biotechnology and Biological Sciences Research Council BB/H003312/1Department of HealthMedical Research Council MC_UU_00014/1Medical Research Council MC_UU_00014/4Medical Research Council MC_UU_00014/5Medical Research Council MC_UU_12012/1Medical Research Council MC_UU_12012/4Medical Research Council MC_UU_12012/5Medical Research Council MRC_MC_UU_12012/4Medical Research Council MRC_MC_UU_12012/5Medical Research Council MR/R022690/1Medical Research Council MR/S026193/1Wellcome TrustWellcome Trust 220456/Z/20/Z
6 · The paper itself

Abstract

In all eutherian mammals, growth of the fetus is dependent upon a functional placenta, but whether and how the latter adapts to putative fetal signals is currently unknown. Here, we demonstrate, through fetal, endothelial, hematopoietic, and trophoblast-specific genetic manipulations in the mouse, that endothelial and fetus-derived IGF2 is required for the continuous expansion of the feto-placental microvasculature in late pregnancy. The angiocrine effects of IGF2 on placental microvasculature expansion are mediated, in part, through IGF2R and angiopoietin-Tie2/TEK signaling. Additionally, IGF2 exerts IGF2R-ERK1/2-dependent pro-proliferative and angiogenic effects on primary feto-placental endothelial cells ex vivo. Endothelial and fetus-derived IGF2 also plays an important role in trophoblast morphogenesis, acting through Gcm1 and Synb. Thus, our study reveals a direct role for the imprinted Igf2-Igf2r axis on matching placental development to fetal growth and establishes the principle that hormone-like signals from the fetus play important roles in controlling placental microvasculature and trophoblast morphogenesis.

Indexed as

AnimalsCell LineDNA-Binding ProteinsEndothelial CellsFemaleFetal DevelopmentFetusInsulin-Like Growth Factor IIMiceMice, Inbred C57BLMicrovesselsNeovascularization, PhysiologicPlacentaPlacentationPregnancyReceptor, IGF Type 2DNA-Binding ProteinsIGF2 protein, mouseIgf2r protein, mouseInsulin-Like Growth Factor IIReceptor, IGF Type 2Transcription Factorsangiogenesisangiopoietinsdevelopmentendothelial cellsfetal growthgenomic imprintingIGF2IGF2Rplacentatrophoblast morphogenesis

Identifiers

PMID34963058
PMCPMC8751640
OpenAlexW4220933249

What OpenQuestion holds

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LicenceCC BY
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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.