Evidence map›Paper›PMID 36581877›Full record

ArticleBMC medicine2022

Chromatin modifier developmental pluripotency associated factor 4 (DPPA4) is a candidate gene for alcohol-induced developmental disorders.

P Auvinen, J Vehviläinen, H Marjonen, V Modhukur, J Sokka, E Wallén, K Rämö, L Ahola, A Salumets, T Otonkoski and 5 more

Open access · goldAbstract read
In one paragraph

Article in BMC medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 17% 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

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.

  1. Pooled it
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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

15 authors at 4 institutions in 3 countries.

P AuvinenEnvironmental Epigenetics Laboratory, Department of Medical and Clinical Genetics, Medicum, University of Helsinki, 00290, Helsinki, Finland.
J VehviläinenEnvironmental Epigenetics Laboratory, Department of Medical and Clinical Genetics, Medicum, University of Helsinki, 00290, Helsinki, Finland.
H MarjonenEnvironmental Epigenetics Laboratory, Department of Medical and Clinical Genetics, Medicum, University of Helsinki, 00290, Helsinki, Finland.
V ModhukurDepartment of Obstetrics and Gynaecology, Institute of Clinical Medicine, University of Tartu, 50406, Tartu, Estonia.
J SokkaResearch Programs Unit, Stem cells and Metabolism and Biomedicum Stem Cell Centre, Faculty of Medicine, University of Helsinki, 00014, Helsinki, Finland.
E WallénEnvironmental Epigenetics Laboratory, Department of Medical and Clinical Genetics, Medicum, University of Helsinki, 00290, Helsinki, Finland.
K RämöEnvironmental Epigenetics Laboratory, Department of Medical and Clinical Genetics, Medicum, University of Helsinki, 00290, Helsinki, Finland.
L AholaEnvironmental Epigenetics Laboratory, Department of Medical and Clinical Genetics, Medicum, University of Helsinki, 00290, Helsinki, Finland.
A SalumetsDepartment of Obstetrics and Gynaecology, Institute of Clinical Medicine, University of Tartu, 50406, Tartu, Estonia.
T OtonkoskiResearch Programs Unit, Stem cells and Metabolism and Biomedicum Stem Cell Centre, Faculty of Medicine, University of Helsinki, 00014, Helsinki, Finland.
H SkottmanFaculty of Medicine and Health Technology, Tampere University, 33520, Tampere, Finland.
M OllikainenInstitute for Molecular Medicine, Finland, FIMM, HiLIFE, University of Helsinki, 00290, Helsinki, Finland.
R TrokovicResearch Programs Unit, Stem cells and Metabolism and Biomedicum Stem Cell Centre, Faculty of Medicine, University of Helsinki, 00014, Helsinki, Finland.
H KahilaObstetrics and Gynecology, Helsinki University Hospital, University of Helsinki, 00290, Helsinki, Finland.
N Kaminen-AholaEnvironmental Epigenetics Laboratory, Department of Medical and Clinical Genetics, Medicum, University of Helsinki, 00290, Helsinki, Finland. nina.kaminen@helsinki.fi.ORCID 0000-0003-1255-4716
University of Helsinki · FICompetence Centre on Health Technologies (Estonia) · EEKarolinska Institutet · SETampere University · FI

Funding

Academy of Finland 297466, 312437Academy of Finland 297886Academy of Finland 297908Academy of Finland 328685Academy of Finland 332212Estonian Research Council PRG1076European Commission and Enterprise Estonia EU48695Finnish Cultural Foundation 00200185Finnish Cultural Foundation 00212573H2020 Innovation ERIN, EU952516Suomen Kulttuurirahasto 00190186
6 · The paper itself

Abstract

backgroundPrenatal alcohol exposure (PAE) affects embryonic development, causing a variable fetal alcohol spectrum disorder (FASD) phenotype with neuronal disorders and birth defects. We hypothesize that early alcohol-induced epigenetic changes disrupt the accurate developmental programming of embryo and consequently cause the complex phenotype of developmental disorders. To explore the etiology of FASD, we collected unique biological samples of 80 severely alcohol-exposed and 100 control newborns at birth.

methodsWe performed genome-wide DNA methylation (DNAm) and gene expression analyses of placentas by using microarrays (EPIC, Illumina) and mRNA sequencing, respectively. To test the manifestation of observed PAE-associated DNAm changes in embryonic tissues as well as potential biomarkers for PAE, we examined if the changes can be detected also in white blood cells or buccal epithelial cells of the same newborns by EpiTYPER. To explore the early effects of alcohol on extraembryonic placental tissue, we selected 27 newborns whose mothers had consumed alcohol up to gestational week 7 at maximum to the separate analyses. Furthermore, to explore the effects of early alcohol exposure on embryonic cells, human embryonic stem cells (hESCs) as well as hESCs during differentiation into endodermal, mesodermal, and ectodermal cells were exposed to alcohol in vitro.

resultsDPPA4, FOXP2, and TACR3 with significantly decreased DNAm were discovered-particularly the regulatory region of DPPA4 in the early alcohol-exposed placentas. When hESCs were exposed to alcohol in vitro, significantly altered regulation of DPPA2, a closely linked heterodimer of DPPA4, was observed. While the regulatory region of DPPA4 was unmethylated in both control and alcohol-exposed hESCs, alcohol-induced decreased DNAm similar to placenta was seen in in vitro differentiated mesodermal and ectodermal cells. Furthermore, common genes with alcohol-associated DNAm changes in placenta and hESCs were linked exclusively to the neurodevelopmental pathways in the enrichment analysis, which emphasizes the value of placental tissue when analyzing the effects of prenatal environment on human development.

conclusionsOur study shows the effects of early alcohol exposure on human embryonic and extraembryonic cells, introduces candidate genes for alcohol-induced developmental disorders, and reveals potential biomarkers for prenatal alcohol exposure.

Indexed as

Fetal Alcohol Spectrum DisordersNuclear ProteinsPrenatal Exposure Delayed EffectsBiomarkersChromatinDevelopmental DisabilitiesEthanolFemaleHumansInfant, NewbornPlacentaPregnancyBiomarkersChromatinDPPA4 protein, humanEthanolNuclear ProteinsDNA methylationDPPA2DPPA4EctodermEmbryonic developmentEndodermEnvironmental epigeneticsFASDFOXP2Gene expressionGerm layersHuman embryonic stem cellsMesodermPAEPlacentaPrenatal alcohol exposureTACR3

Identifiers

PMID36581877
PMCPMC9801659
OpenAlexW4313331458

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.