Evidence map›Paper›PMID 26401051›Full record

ArticleHuman molecular genetics2015

The cumulative effect of assisted reproduction procedures on placental development and epigenetic perturbations in a mouse model.

Eric de Waal, Lisa A Vrooman, Erin Fischer, Teri Ord, Monica A Mainigi, Christos Coutifaris, Richard M Schultz, Marisa S Bartolomei

Open access · bronzeAbstract read
In one paragraph

Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed, 2 pooled it
26.4field-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

91 citing papers in PubMed, 2 syntheses or guidelines pooled it, 158 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Review
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31 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

8 authors at 1 institution in 1 country.

Eric de WaalDepartment of Cell and Developmental Biology.
Lisa A VroomanDepartment of Cell and Developmental Biology.
Erin FischerDepartment of Cell and Developmental Biology.
Teri OrdDepartment of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA and.
Monica A MainigiDepartment of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA and.
Christos CoutifarisDepartment of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA and.
Richard M SchultzDepartment of Biology, University of Pennsylvania, Philadelphia, PA, USA.
Marisa S BartolomeiDepartment of Cell and Developmental Biology, bartolom@mail.med.upenn.edu.
University of Pennsylvania · US

Funding

Translational Research Support CoreP30ES013508 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Rebecca A Simmons · 2006 to 2026
$35.3M
Research Project 4: Epigenetic Regulation of Retrotransposon Silencing and Male Fertility in the MouseP50HD068157 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI Suneeta Senapati · 2014 to 2026
$16.3M
Translational Research Training Program in Environmental Health SciencesT32ES019851 · NIEHS · UNIVERSITY OF PENNSYLVANIA · PI Kara A Bernstein, Trevor M Penning · 2012 to 2026
$6.0M
PROJECT 4: TARGETING ADP-RIBOSE POLYMER DEPENDENT EPIGENETIC EVENTS IN MALE LINEU54HD068157 · NICHD · UNIVERSITY OF PENNSYLVANIA · PI COUTIFARIS, CHRISTOS · 2011 to 2013
$4.8M
NICHD NIH HHS HD068157NICHD NIH HHS P50 HD068157NICHD NIH HHS U54 HD068157NIEHS NIH HHS T32 ES019851NIEHS NIH HHS T32ES019851
6 · The paper itself

Abstract

Assisted reproductive technologies (ART) are associated with several complications including low birth weight, abnormal placentation and increased risk for rare imprinting disorders. Indeed, experimental studies demonstrate ART procedures independent of existing infertility induce epigenetic perturbations in the embryo and extraembryonic tissues. To test the hypothesis that these epigenetic perturbations persist and result in adverse outcomes at term, we assessed placental morphology and methylation profiles in E18.5 mouse concepti generated by in vitro fertilization (IVF) in two different genetic backgrounds. We also examined embryo transfer (ET) and superovulation procedures to ascertain if they contribute to developmental and epigenetic effects. Increased placental weight and reduced fetal-to-placental weight ratio were observed in all ART groups when compared with naturally conceived controls, demonstrating that non-surgical embryo transfer alone can impact placental development. Furthermore, superovulation further induced overgrowth of the placental junctional zone. Embryo transfer and superovulation defects were limited to these morphological changes, as we did not observe any differences in epigenetic profiles. IVF placentae, however, displayed hypomethylation of imprinting control regions of select imprinted genes and a global reduction in DNA methylation levels. Although we did not detect significant differences in DNA methylation in fetal brain or liver samples, rare IVF concepti displayed very low methylation and abnormal gene expression from the normally repressed allele. Our findings suggest that individual ART procedures cumulatively increase placental morphological abnormalities and epigenetic perturbations, potentially causing adverse neonatal and long-term health outcomes in offspring.

Indexed as

EpigenomicsPlacentationAllelesAmino Acid Transport System AAnimalsCrosses, GeneticDNA MethylationEmbryo TransferFemaleFertilization in VitroFetusGene ExpressionGlucose Transporter Type 1Glucose Transporter Type 3MaleMiceAmino Acid Transport System AGlucose Transporter Type 1Glucose Transporter Type 3Slc2a1 protein, mouseSlc2a3 protein, mouseSlc38a2 protein, mouseSlc38a4 protein, mouse

Identifiers

PMID26401051
PMCPMC4654053
OpenAlexW2178425085

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.