Evidence map›Paper›PMID 29691980›Full record

ArticleJournal of cellular and molecular medicine2018

Glucocorticoids modulate multidrug resistance transporters in the first trimester human placenta.

Phetcharawan Lye, Enrrico Bloise, Lubna Nadeem, William Gibb, Stephen J Lye, Stephen G Matthews

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cellular and molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 14% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

  1. Pooled it
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  14. Overview of Drug Transporters in Human Placenta.International journal of molecular sciences · 2021
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  15. Article
  16. Transcription factor-mediated regulation of the BCRP/Expert opinion on drug metabolism & toxicology · 2020
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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

6 authors at 4 institutions in 2 countries.

Phetcharawan LyeDepartment of Physiology, University of Toronto, Toronto, ON, Canada.
Enrrico BloiseDepartment of Physiology, University of Toronto, Toronto, ON, Canada.ORCID 0000-0003-0275-8686
Lubna NadeemLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
William GibbDepartment of Obstetrics & Gynaecology, University of Ottawa, Ottawa, ON, Canada.
Stephen J LyeDepartment of Physiology, University of Toronto, Toronto, ON, Canada.
Stephen G MatthewsDepartment of Physiology, University of Toronto, Toronto, ON, Canada.
Mount Sinai Hospital · CAUniversidade Federal de Minas Gerais · BRUniversity of Ottawa · CAUniversity of Toronto · CA

Funding

CIHR FDN‐148368
6 · The paper itself

Abstract

The placental multidrug transporters, P-glycoprotein (P-gp, encoded by ABCB1) and breast cancer resistance protein (BCRP, ABCG2) protect the foetus from exposure to maternally derived glucocorticoids, toxins and xenobiotics. During pregnancy, maternal glucocorticoid levels can be elevated by stress or exogenous administration. We hypothesized that glucocorticoids modulate the expression of ABCB1/P-gp and ABCG2/BCRP in the first trimester human placenta. Our objective was to examine whether dexamethasone (DEX) or cortisol modulate first trimester placental expression of multidrug transporters and determine whether cytotrophoblasts or the syncytiotrophoblast are/is responsible for mediating these effects. Three models were examined: (i) an ex-vivo model of placental villous explants (7-10 weeks), (ii) a model of isolated first trimester syncytiotrophoblast and cytotrophoblast cells and (iii) the BeWo immortalized trophoblast cell line model. These cells/tissues were treated with DEX or cortisol for 24 hour to 72 hour. In first trimester placental explants, DEX (48 hour) increased ABCB1 (P < .001) and ABCG2 (P < .05) mRNA levels, whereas cortisol (48 hour) only increased ABCB1 mRNA levels (P < .01). Dexamethasone (P < .05) and cortisol (P < .01) increased BCRP but did not affect P-gp protein levels. Breast cancer resistance protein expression was primarily confined to syncytiotrophoblasts. BeWo cells, when syncytialized with forskolin, increased expression of BCRP protein, and this was further augmented by DEX (P < .05). Our data suggest that the protective barrier provided by BCRP increases as cytotrophoblasts fuse to form the syncytiotrophoblast. Increase in glucocorticoid levels during the first trimester may reduce embryo/foetal exposure to clinically relevant BCRP substrates, because of an increase in placental BCRP.

Indexed as

ATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily G, Member 2DexamethasoneFemaleGlucocorticoidsHumansHydrocortisoneNeoplasm ProteinsOrgan Culture TechniquesPlacentaPregnancyPregnancy Trimester, FirstTrophoblastsABCB1 protein, humanABCG2 protein, humanATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1ATP Binding Cassette Transporter, Subfamily G, Member 2DexamethasoneGlucocorticoidsHydrocortisoneNeoplasm ProteinsBeWobreast cancer related protein (BCRP)dexamethasonefirst trimester placentaglucocorticoidsP-glycoprotein (P-gp)

Identifiers

PMID29691980
PMCPMC6010777
OpenAlexW2800913882

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.