Evidence map›Paper›PMID 30572800›Full record

ArticleReproductive sciences (Thousand Oaks, Calif.)2019

Cell-Free DNA Release by Mouse Fetal Membranes.

Michala R Sawyer, Sharareh Adeli, Mark Phillippe

Abstract read
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In one paragraph

Article in Reproductive sciences (Thousand Oaks, Calif.), 2019. 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
0.7field-weighted citation impact, top 21% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

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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

3 authors at 2 institutions in 1 country.

Michala R SawyerDivision of Maternal-Fetal Medicine and the Vincent Center for Reproductive Biology, Department of Obstetrics & Gynecology, Massachusetts General Hospital, 55 Fruit Street, Thier Bldg. 9-911, Boston, MA, 02114, USA.
Sharareh AdeliDivision of Maternal-Fetal Medicine and the Vincent Center for Reproductive Biology, Department of Obstetrics & Gynecology, Massachusetts General Hospital, 55 Fruit Street, Thier Bldg. 9-911, Boston, MA, 02114, USA.
Mark PhillippeDivision of Maternal-Fetal Medicine and the Vincent Center for Reproductive Biology, Department of Obstetrics & Gynecology, Massachusetts General Hospital, 55 Fruit Street, Thier Bldg. 9-911, Boston, MA, 02114, USA. mphillippe@mgh.harvard.edu.
Massachusetts General Hospital · USSaint Vincent Hospital · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionCell-free "fetal" DNA is released from the placenta. Because the fetal membranes also arise from the trophectoderm layer of the blastocyst, these studies sought to test the hypothesis that the membranes also release cell-free DNA (cfDNA).

methodsFetal membranes were harvested from pregnant CD-1 mice and cultured in 12-well plates containing media alone or with staurosporine and thapsigargin (apoptosis stimulators), Q-VD-OPh (caspase inhibitor), Trolox (vitamin E analog), and lipopolysaccharide and tumor necrosis factor α (TNFα; inflammatory mediators). The cfDNA in the media was extracted, quantified, and normalized for tissue weight. Media was used for a lactate dehydrogenase (LDH) assay. Membrane homogenates were used to assess activated caspase levels and the expression of DNA fragmentation factor B (DFFB) and BAX proteins. 5-Methylcytosine was assessed using a 5-mC DNA enzyme-linked immunosorbent assay. The cfDNA was used to stimulate interleukin 6 (IL6) release by J774A.1 mouse macrophage cells.

resultsIncreased cfDNA release at 6 and 21 hours occurred in parallel with increasing LDH levels. The cfDNA concentrations were significantly suppressed by Q-VD-OPh and Trolox and increased by thapsigargin and TNFα. Increased caspase activity was suppressed by Q-VD-OPh and increased by TNFα, thapsigargin, and staurosporine. The expression of BAX and DFFB proteins significantly increased by 21 hours. 5-Methylcytosine levels were significantly lower in fetal membranes and placentas and below detectable in the cfDNA released by the explants. The cfDNA-stimulated IL6 release by macrophage cells was suppressed by chloroquine, a Toll-like receptor 9 (TLR9) inhibitor.

conclusionsThese studies have confirmed cfDNA release by the mouse fetal membranes; cfDNA was markedly hypomethylated and a robust stimulator of TLR9.

Indexed as

5-MethylcytosineAmino Acid Chloromethyl KetonesAnimalsApoptosisCaspase InhibitorsCell-Free Nucleic AcidsCulture Media, ConditionedExtraembryonic MembranesFemaleMicePlacentaPregnancyQuinolinesSignal TransductionThapsigargin5-MethylcytosineAmino Acid Chloromethyl KetonesCaspase InhibitorsCell-Free Nucleic AcidsCulture Media, ConditionedQuinolinesquinoline-val-asp(OMe)-CH2-OPHThapsigarginapoptosisDNA methylationfetal cell-free DNAfetal membrane explantsToll-like receptor 9

Identifiers

PMID30572800
OpenAlexW2906506696

What OpenQuestion holds

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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.