Summary of Study ST001310

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000891. The data can be accessed directly via it's Project DOI: 10.21228/M8HM5N This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST001310
Study TitleC57 midgestation placental metabolomics analysis
Study TypeBPA, BPS exposure on placenta metabolite profile
Study SummaryPlacental trophoblast cells are potentially at risk from circulating endocrine-disrupting chemicals, such as bisphenol A (BPA). To understand how BPA and the reputedly more inert bisphenol S (BPS) affect the placenta, C57BL6J mouse dams were fed 200 μg/kg body weight BPA or BPS daily for 2 wk and then bred. They continued to receive these chemicals until embryonic day 12.5, whereupon placental samples were collected and compared with unexposed controls. BPA and BPS altered the expression of an identical set of 13 genes. Both exposures led to a decrease in the area occupied by spongiotrophoblast relative to multinucleated giant cells (GCs) within the junctional zone, markedly reduced placental serotonin (5-HT) concentrations, and lowered 5-HT GC immunoreactivity. Concentrations of dopamine and 5-hydroxyindoleacetic acid, the main metabolite of serotonin, were increased. GC dopamine immunoreactivity was increased in BPA- and BPS-exposed placentas. A strong positive correlation between 5-HT+ GCs and reductions in spongiotrophoblast to GC area suggests that this neurotransmitter is essential for maintaining cells within the junctional zone. In contrast, an inverse correlation existed between dopamine+ GCs and reductions spongiotrophoblast to GC area. These outcomes lead to the following conclusions. First, BPS exposure causes almost identical placental effects as BPA. Second, a major target of BPA/BPS is either spongiotrophoblast or GC within the junctional zone. Third, imbalances in neurotransmitter-positive GC and an observed decrease in docosahexaenoic acid and estradiol, also occurring in response to BPA/BPS exposure, likely affect the placental–brain axis of the developing mouse fetus.
Institute
University of Missouri
DepartmentLife Sciences Center
LaboratoryUniv. of Missouri Metabolomics Center
Last NameSumner
First NameLloyd
Address1201 Rollins Street Columbia, Missouri 65211-7310
Emailsumnerlw@missouri.edu
Phone573-882-5486
Submit Date2020-01-27
Num Groups3 treatment X 2 sex = 6
Total Subjects40
PublicationsMao et al, Proceedings National Academy of Science, USA, 2020
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailGC-MS
Release Date2020-03-03
Release Version1
Lloyd Sumner Lloyd Sumner
https://dx.doi.org/10.21228/M8HM5N
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000891
Project DOI:doi: 10.21228/M8HM5N
Project Title:Bisphenol A and bisphenol S disruptions of the mouse placenta and potential effects on the placenta–brain axis
Project Summary:Placental trophoblast cells are potentially at risk from circulating endocrine-disrupting chemicals, such as bisphenol A (BPA). To understand how BPA and the reputedly more inert bisphenol S (BPS) affect the placenta, C57BL6J mouse dams were fed 200 μg/kg body weight BPA or BPS daily for 2 wk and then bred. They continued to receive these chemicals until embryonic day 12.5, whereupon placental samples were collected and compared with unexposed controls. BPA and BPS altered the expression of an identical set of 13 genes. Both exposures led to a decrease in the area occupied by spongiotrophoblast relative to multinucleated giant cells (GCs) within the junctional zone, markedly reduced placental serotonin (5-HT) concentrations, and lowered 5-HT GC immunoreactivity. Concentrations of dopamine and 5-hydroxyindoleacetic acid, the main metabolite of serotonin, were increased. GC dopamine immunoreactivity was increased in BPA- and BPS-exposed placentas. A strong positive correlation between 5-HT+ GCs and reductions in spongiotrophoblast to GC area suggests that this neurotransmitter is essential for maintaining cells within the junctional zone. In contrast, an inverse correlation existed between dopamine+ GCs and reductions spongiotrophoblast to GC area. These outcomes lead to the following conclusions. First, BPS exposure causes almost identical placental effects as BPA. Second, a major target of BPA/BPS is either spongiotrophoblast or GC within the junctional zone. Third, imbalances in neurotransmitter-positive GC and an observed decrease in docosahexaenoic acid and estradiol, also occurring in response to BPA/BPS exposure, likely affect the placental–brain axis of the developing mouse fetus.
Institute:University of Missouri
Department:Life Sciences Center
Laboratory:Rosenfeld Lab
Last Name:Rosenfeld
First Name:Cheryl
Address:Bond Life Sciences Center, 1201 Rollins St., Columbia, MO
Email:RosenfeldC@missouri.edu
Phone:573-882-5132
Funding Source:NIEHS
Publications:Mao et al, Proceedings National Academy of Science, USA,
Contributors:Jiude Mao, Ashish Jain, Nancy D. Denslow, Mohammad-Zaman Nouri, Sixue Chen, Tingting Wang, Ning Zhu, Jin Koh, Saurav J. Sarma, Barbara W. Sumner, Zhentian Lei, Lloyd W. Sumner, Nathan J. Bivens, R. Michael Roberts, Geetu Tuteja, and Cheryl S. Rosenfeld

Subject:

Subject ID:SU001384
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Genotype Strain:C57BL6J
Age Or Age Range:Embryonic day 12.5
Gender:Male and female
Animal Animal Supplier:Jackson Labs
Animal Housing:polypropylene cages

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Exposure Gender
SA0946193017-BPA-FBPA female
SA0946203018-BPA-FBPA female
SA0946212021-BPA-FBPA female
SA0946223015-BPA-FBPA female
SA0946232027-BPA-FBPA female
SA0946242015-BPA-FBPA female
SA0946252015-BPA-MBPA male
SA0946262021-BPA-MBPA male
SA0946273018-BPA-MBPA male
SA0946282027-BPA-MBPA male
SA0946293017-BPA-MBPA male
SA0946302009-BPA-MBPA male
SA0946313015-BPA-MBPA male
SA0946322009-BPS-FBPS female
SA0946332007-BPS-FBPS female
SA0946342031-BPS-FBPS female
SA0946353002-BPS-FBPS female
SA0946362019-BPS-FBPS female
SA0946372013-BPS-FBPS female
SA0946382025-BPS-FBPS female
SA0946392001-BPS-FBPS female
SA0946403004-BPS-FBPS female
SA0946413002-BPS-MBPS male
SA0946422007-BPS-MBPS male
SA0946432013-BPS-MBPS male
SA0946442031-BPS-MBPS male
SA0946452025-BPS-MBPS male
SA0946462019-BPS-MBPS male
SA0946472001-BPS-MBPS male
SA0946483004-BPS-MBPS male
SA0946492017-Control-FCTRL female
SA0946503008-Control-FCTRL female
SA0946513009-Control-FCTRL female
SA0946522029-Control-FCTRL female
SA0946532005-Control-FCTRL female
SA0946542017-Control-MCTRL male
SA0946553008-Control-MCTRL male
SA0946562005-Control-MCTRL male
SA0946573009-Control-MCTRL male
SA0946582029-Control-MCTRL male
Showing results 1 to 40 of 40

Collection:

Collection ID:CO001379
Collection Summary:e12.5 placenta samples were collected immediately after dams were euthanized
Sample Type:Placenta
Collection Method:snap freezen in LN2 right after placenta was isolated
Collection Location:Univ. of Missouri Animal Science Research Center
Collection Frequency:1 time from each animal
Volumeoramount Collected:50 mg
Storage Vials:1.5 ml vials

Treatment:

Treatment ID:TR001399
Treatment Summary:2 weeks before breeding and during gestation, dams were fed BPA, or BPS, or vehicle till tissue collection at 12.5 DPC
Treatment Compound:Bisphenol A, bisphenol S
Treatment Route:oral
Treatment Dose:200 microg/kg body weight
Treatment Vehicle:70% ethanol dry out onto Nabisco Nilla wafer
Animal Endp Euthanasia:yes

Sample Preparation:

Sampleprep ID:SP001392
Sampleprep Summary:Freshly isolated mouse placneta tissue was snap frozen in liqud nitrogen and no further preparation. Samples were storred at -52C in lyophilyzer and -20C after weighing. Extracts were dried under nitrogen flow and stored at -20C
Processing Method:Frozen tissues were lyophilized for 24 hrs before weighing.
Processing Storage Conditions:Described in summary
Extraction Method:samples were extracted water, containing 25 μg/ml ribitol, vortex for 20 seconds, sonicated for 15 minutes, incubated at 50C for 1h
Extract Enrichment:Sample tubes were sonicated for 15 minutes at 13000g then collected the supernatantant
Extract Storage:-20℃
Sample Resuspension:Sample was resuspended in 25 μl of pyridine containing 15 mg/ml methoxyamine hydrochloride
Sample Derivatization:Sample was derivatized with 25 μl MSTFA (N-methyl-N-(trimethyl-silyl)trifluoroacetamide) + 1% TMCS (chlorotrimethylsilane)
Sample Spiking:Ribitol was used in the extraction solvent as an internal standard

Combined analysis:

Analysis ID AN002181
Analysis type MS
Chromatography type GC
Chromatography system Agilent 6890N;Agilent 5973N
Column DB-5MS (J&W Scientific)
MS Type EI
MS instrument type Single quadrupole
MS instrument name Agilent 5973
Ion Mode POSITIVE
Units relative instrument response

Chromatography:

Chromatography ID:CH001596
Chromatography Comments:Agilent 6890N coupled to an Agilent 5973N
Instrument Name:Agilent 6890N;Agilent 5973N
Column Name:DB-5MS (J&W Scientific)
Column Temperature:80 C for 2 min, then ramped at 5 C /min to 315 C and held at 315 C for 12 min
Flow Rate:1mL/Min of Helium gas
Injection Temperature:280 C
Internal Standard:Ribitol
Sample Injection:split injection (split ration 5:1) with 1uL injection volume
Chromatography Type:GC

MS:

MS ID:MS002028
Analysis ID:AN002181
Instrument Name:Agilent 5973
Instrument Type:Single quadrupole
MS Type:EI
MS Comments:70 eV electron ionization
Ion Mode:POSITIVE
Ion Source Temperature:230 C
Mass Accuracy:0.1 m/z
Dataformat:.D
Scan Range Moverz:50 to 650 m/z
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