Evidence map›Paper›PMID 33827559›Full record

ArticleBMC medicine2021

Dexamethasone induces an imbalanced fetal-placental-maternal bile acid circulation: involvement of placental transporters.

Wen Huang, Jin Zhou, Juanjuan Guo, Wen Hu, Guanghui Chen, Bin Li, Yajie Wen, Yimin Jiang, Kaili Fu, Huichang Bi and 2 more

Open access · goldAbstract read
In one paragraph

Article in BMC medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.1field-weighted citation impact, top 10% 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

10 citing papers in PubMed, 28 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

12 authors at 2 institutions in 1 country.

Wen Huang *Department of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Jin Zhou *Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 430071, China.
Juanjuan GuoDepartment of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Wen HuDepartment of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 430071, China.
Guanghui ChenDepartment of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 430071, China.
Bin LiDepartment of Pharmacology, Basic Medical School of Wuhan University, Wuhan, 430071, China.
Yajie WenSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Yimin JiangSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Kaili FuSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China.
Huichang BiSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China. bihuichang@mail.sysu.edu.cn.
Yuanzhen ZhangDepartment of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. zhangyuanzhen@vip.sina.com.
Hui WangDepartment of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. wanghui19@whu.edu.cn.ORCID 0000-0001-5300-8661
Wuhan University · CNSun Yat-sen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe use of prenatal dexamethasone remains controversial. Our recent studies found that prenatal dexamethasone exposure can induce maternal intrahepatic cholestasis and have a lasting adverse influence on bile acid (BA) metabolism in the offspring. The purpose of this study was to investigate the effects of dexamethasone on fetal-placental-maternal BA circulation during the intrauterine period, as well as its placental mechanism.

methodsClinical data and human placentas were collected and analyzed. Pregnant Wistar rats were injected subcutaneously with dexamethasone (0.2 mg/kg per day) from gestational day 9 to 20. The metabolomic spectra of BAs in maternal and fetal rat serum were determined by LC-MS. Human and rat placentas were collected for histological and gene expression analysis. BeWo human placental cell line was treated with dexamethasone (20-500 nM).

resultsHuman male neonates born after prenatal dexamethasone treatment showed an increased serum BA level while no significant change was observed in females. Moreover, the expression of organic anion transporter polypeptide-related protein 2B1 (OATP2B1) and breast cancer resistance protein (BCRP) in the male neonates' placenta was decreased, while multidrug resistance-associated protein 4 (MRP4) was upregulated. In experimental rats, dexamethasone increased male but decreased female fetal serum total bile acid (TBA) level. LC-MS revealed that primary BAs were the major component that increased in both male and female fetal serum, and all kinds of BAs were significantly increased in maternal serum. The expression of Oatp2b1 and Bcrp were reduced, while Mrp4 expression was increased in the dexamethasone-treated rat placentas. Moreover, dexamethasone increased glucocorticoid receptor (GR) expression and decreased farnesoid X receptor (FXR) expression in the rat placenta. In BeWo cells, dexamethasone induced GR translocation into the nucleus; decreased FXR, OATP2B1, and BCRP expression; and increased MRP4 expression. Furthermore, GR was verified to mediate the downregulation of OATP2B1, while FXR mediated dexamethasone-altered expression of BCRP and MRP4.

conclusionsBy affecting placental BA transporters, dexamethasone induces an imbalanced fetal-placental-maternal BA circulation, as showed by the increase of primary BA levels in the fetal serum. This study provides an important experimental and theoretical basis for elucidating the mechanism of dexamethasone-induced alteration of maternal and fetal BA metabolism and for exploring early prevention and treatment strategies.

Indexed as

Bile Acids and SaltsPlacentaAnimalsATP Binding Cassette Transporter, Subfamily G, Member 2DexamethasoneFemaleMaleNeoplasm ProteinsPregnancyRatsRats, WistarATP Binding Cassette Transporter, Subfamily G, Member 2Bile Acids and SaltsDexamethasoneNeoplasm ProteinsBile acidsDexamethasoneFarnesoid X receptorGlucocorticoid receptorPlacentaTransporters

Identifiers

PMID33827559
PMCPMC8028715
OpenAlexW3140556811

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.