Evidence map›Paper›PMID 37164652›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2023

Characterization of Xenobiotic and Steroid Disposition Potential of Human Placental Tissue and Cell Lines (BeWo, JEG-3, JAR, and HTR-8/SVneo) by Quantitative Proteomics.

Laken Kruger, Samantha Lapehn, Alison Paquette, Dilip Kumar Singh, James MacDonald, Theo K Bammler, Daniel A Enquobahrie, Qi Zhao, Khyobeni Mozhui, Sheela Sathyanarayana and 1 more

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

Article in Drug metabolism and disposition: the biological fate of chemicals, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 22% 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

7 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Current approaches and advances in placental toxicology.Trends in endocrinology and metabolism: TEM · 2026
    Review
  5. Article
  6. Transcriptomic comparison of in vitro models of the human placenta.bioRxiv : the preprint server for biology · 2024
    Article
  7. Article
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

11 authors at 3 institutions in 1 country.

Laken KrugerDepartment of Pharmaceutical Sciences, Washington State University, Spokane, Washington (L.K., D.K.S., B.P.); Centers for Developmental Biology and Regenerative Medicine (S.L., A.P.) and Child Health, Behavior and Development (S.S.), Seattle Children's Research Institute, Seattle, Washington; Departments of Pediatrics (A.P., S.S.), Environmental and Occupational Health Sciences (J.M., T.K.B., S.S.), and Epidemiology (D.A.E.), University of Washington, Seattle, Washington; and Department of Preventative Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee (K.M., Q.Z.).
Samantha LapehnDepartment of Pharmaceutical Sciences, Washington State University, Spokane, Washington (L.K., D.K.S., B.P.); Centers for Developmental Biology and Regenerative Medicine (S.L., A.P.) and Child Health, Behavior and Development (S.S.), Seattle Children's Research Institute, Seattle, Washington; Departments of Pediatrics (A.P., S.S.), Environmental and Occupational Health Sciences (J.M., T.K.B., S.S.), and Epidemiology (D.A.E.), University of Washington, Seattle, Washington; and Department of Preventative Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee (K.M., Q.Z.).
Alison PaquetteDepartment of Pharmaceutical Sciences, Washington State University, Spokane, Washington (L.K., D.K.S., B.P.); Centers for Developmental Biology and Regenerative Medicine (S.L., A.P.) and Child Health, Behavior and Development (S.S.), Seattle Children's Research Institute, Seattle, Washington; Departments of Pediatrics (A.P., S.S.), Environmental and Occupational Health Sciences (J.M., T.K.B., S.S.), and Epidemiology (D.A.E.), University of Washington, Seattle, Washington; and Department of Preventative Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee (K.M., Q.Z.).
Dilip Kumar SinghDepartment of Pharmaceutical Sciences, Washington State University, Spokane, Washington (L.K., D.K.S., B.P.); Centers for Developmental Biology and Regenerative Medicine (S.L., A.P.) and Child Health, Behavior and Development (S.S.), Seattle Children's Research Institute, Seattle, Washington; Departments of Pediatrics (A.P., S.S.), Environmental and Occupational Health Sciences (J.M., T.K.B., S.S.), and Epidemiology (D.A.E.), University of Washington, Seattle, Washington; and Department of Preventative Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee (K.M., Q.Z.).
James MacDonaldDepartment of Pharmaceutical Sciences, Washington State University, Spokane, Washington (L.K., D.K.S., B.P.); Centers for Developmental Biology and Regenerative Medicine (S.L., A.P.) and Child Health, Behavior and Development (S.S.), Seattle Children's Research Institute, Seattle, Washington; Departments of Pediatrics (A.P., S.S.), Environmental and Occupational Health Sciences (J.M., T.K.B., S.S.), and Epidemiology (D.A.E.), University of Washington, Seattle, Washington; and Department of Preventative Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee (K.M., Q.Z.).
Theo K BammlerDepartment of Pharmaceutical Sciences, Washington State University, Spokane, Washington (L.K., D.K.S., B.P.); Centers for Developmental Biology and Regenerative Medicine (S.L., A.P.) and Child Health, Behavior and Development (S.S.), Seattle Children's Research Institute, Seattle, Washington; Departments of Pediatrics (A.P., S.S.), Environmental and Occupational Health Sciences (J.M., T.K.B., S.S.), and Epidemiology (D.A.E.), University of Washington, Seattle, Washington; and Department of Preventative Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee (K.M., Q.Z.).
Daniel A EnquobahrieDepartment of Pharmaceutical Sciences, Washington State University, Spokane, Washington (L.K., D.K.S., B.P.); Centers for Developmental Biology and Regenerative Medicine (S.L., A.P.) and Child Health, Behavior and Development (S.S.), Seattle Children's Research Institute, Seattle, Washington; Departments of Pediatrics (A.P., S.S.), Environmental and Occupational Health Sciences (J.M., T.K.B., S.S.), and Epidemiology (D.A.E.), University of Washington, Seattle, Washington; and Department of Preventative Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee (K.M., Q.Z.).
Qi ZhaoDepartment of Pharmaceutical Sciences, Washington State University, Spokane, Washington (L.K., D.K.S., B.P.); Centers for Developmental Biology and Regenerative Medicine (S.L., A.P.) and Child Health, Behavior and Development (S.S.), Seattle Children's Research Institute, Seattle, Washington; Departments of Pediatrics (A.P., S.S.), Environmental and Occupational Health Sciences (J.M., T.K.B., S.S.), and Epidemiology (D.A.E.), University of Washington, Seattle, Washington; and Department of Preventative Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee (K.M., Q.Z.).
Khyobeni MozhuiDepartment of Pharmaceutical Sciences, Washington State University, Spokane, Washington (L.K., D.K.S., B.P.); Centers for Developmental Biology and Regenerative Medicine (S.L., A.P.) and Child Health, Behavior and Development (S.S.), Seattle Children's Research Institute, Seattle, Washington; Departments of Pediatrics (A.P., S.S.), Environmental and Occupational Health Sciences (J.M., T.K.B., S.S.), and Epidemiology (D.A.E.), University of Washington, Seattle, Washington; and Department of Preventative Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee (K.M., Q.Z.).
Sheela SathyanarayanaDepartment of Pharmaceutical Sciences, Washington State University, Spokane, Washington (L.K., D.K.S., B.P.); Centers for Developmental Biology and Regenerative Medicine (S.L., A.P.) and Child Health, Behavior and Development (S.S.), Seattle Children's Research Institute, Seattle, Washington; Departments of Pediatrics (A.P., S.S.), Environmental and Occupational Health Sciences (J.M., T.K.B., S.S.), and Epidemiology (D.A.E.), University of Washington, Seattle, Washington; and Department of Preventative Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee (K.M., Q.Z.).
Bhagwat PrasadDepartment of Pharmaceutical Sciences, Washington State University, Spokane, Washington (L.K., D.K.S., B.P.); Centers for Developmental Biology and Regenerative Medicine (S.L., A.P.) and Child Health, Behavior and Development (S.S.), Seattle Children's Research Institute, Seattle, Washington; Departments of Pediatrics (A.P., S.S.), Environmental and Occupational Health Sciences (J.M., T.K.B., S.S.), and Epidemiology (D.A.E.), University of Washington, Seattle, Washington; and Department of Preventative Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee (K.M., Q.Z.) bhagwat.prasad@wsu.edu.ORCID 0000-0002-9090-0912
University of Washington · USSeattle Children's Hospital · USUniversity of Tennessee Health Science Center · US

Funding

XENOBIOTIC BIOTRANSFORMATION AND DISPOSITIONP30ES007033 · NIEHS · UNIVERSITY OF WASHINGTON · PI Nicole Ann Errett · 1995 to 2026
$42.5M
Prenatal and Early Childhood Pathways To Health:  An Integrated Model of Chemical and Social Exposures, Biological Mechanisms, and Sex-Specific Effects on Neurodevelopment and Respiratory OutcomesUH3OD023271 · OD · UNIVERSITY OF WASHINGTON · PI BUSH, NICOLE RENEE, KARR, CATHERINE J · 2018 to 2022
$37.3M
Prenatal and Early Childhood Pathways To Health:  An Integrated Model of Chemical and Social Exposures, Biological Mechanisms, and Sex-Specific Effects on Neurodevelopment and Respiratory OutcomesUG3OD023271 · OD · UNIVERSITY OF WASHINGTON · PI BUSH, NICOLE RENEE, KARR, CATHERINE J · 2016 to 2017
$5.1M
The Role of Corticotrophin Releasing Hormone on Placental Transcriptional Networks and Birth TimingR00HD096112 · NICHD · SEATTLE CHILDREN'S HOSPITAL · PI PAQUETTE, ALISON GENEVIEVE · 2020 to 2022
$721k
NHLBI NIH HHS R01 HL1009977NICHD NIH HHS R00 HD096112NIEHS NIH HHS P30 ES007033NIH HHS UG3 OD023271NIH HHS UH3 OD023271
6 · The paper itself

Abstract

The placenta is a fetal organ that performs critical functions to maintain pregnancy and support fetal development, including metabolism and transport of xenobiotics and steroids between the maternal-fetal unit. In vitro placenta models are used to study xenobiotic and steroid disposition, but how well these models recapitulate the human placenta is not well understood. We first characterized the abundance of proteins involved in xenobiotic and steroid disposition in human placental tissue. In pooled human placenta, the following xenobiotic and steroid disposition proteins were detected (highest to lowest), 1) enzymes: glutathione S-transferase P, carbonyl reductase 1, aldo-keto reductase 1B1, hydroxysteroid dehydrogenases (HSD3B1 and HSD11B1), aromatase, epoxide hydrolase 1 (EPHX1) and steryl-sulfatase, and 2) transporters: monocarboxylate transporters (MCT1 and 4), organic anion transporting polypeptide 2B1, organic anion transporter 4, and breast cancer resistance protein (BCRP). Then, the tissue proteomics data were compared with four placental cell lines (BeWo, JEG-3, JAR, and HTR-8/SVneo). The differential global proteomics analysis revealed that the tissue and cell lines shared 1420 cytosolic and 1186 membrane proteins. Although extravillous trophoblast and cytotrophoblast marker proteins were detected in all cell lines, only BeWo and JEG-3 cells expressed the syncytiotrophoblast marker, chorionic somatomammotropin hormone 1. BeWo and JEG-3 cells expressed most target proteins including aromatase, HSDs, EPHX1, MCT1, and BCRP. JEG-3 cells treated with commonly detected phthalates in human biofluids showed dysregulation of steroid pathways. The data presented here show that BeWo and JEG-3 cells are closer to the placental tissue for studying xenobiotic and steroid disposition. SIGNIFICANCE STATEMENT: This is the first study to compare proteomics data of human placental tissue and cell lines (BeWo, JAR, JEG-3, and HTR-8/SVneo). The placental cell line and tissue proteomes are vastly different, but BeWo and JEG-3 cells showed greater resemblance to the tissue in the expression of xenobiotic and steroid disposition proteins. These data will assist researchers to select an optimum cell model for mechanistic investigations on xenobiotic and steroid disposition in the placenta.

Indexed as

AromatasePlacentaATP Binding Cassette Transporter, Subfamily G, Member 2Cell Line, TumorFemaleHumansNeoplasm ProteinsPregnancyProteomicsSteroidsXenobioticsAromataseATP Binding Cassette Transporter, Subfamily G, Member 2Neoplasm ProteinsSteroidsXenobiotics

Identifiers

PMID37164652
PMCPMC10353074
OpenAlexW4376111482

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.