Summary of Study ST003130

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 PR001943. The data can be accessed directly via it's Project DOI: 10.21228/M8K43P 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 IDST003130
Study TitlePulmonary maternal immune activation does not extend through the placenta but leads to fetal metabolic adaptation - Maternal blood
Study SummaryMaternal immune system activation (MIA) during pregnancy can disrupt the fetal environment, causing postnatal susceptibility to disorders. How the placenta and the fetus respond to acute MIA over time is unknown. Here, we characterized the response to acute maternal pulmonary inflammation across time in maternal and fetal organs using multi-omics. Unlike maternal organs which mounted strong innate immune responses, the placenta upregulated tissue-integrity genes, likely to prevent fetal exposure to infections, and downregulated growth-associated genes. Subsequently, the placenta upregulated biosynthesis and endoplasmic reticulum stress genes in order to return to homeostasis. These responses likely protected the fetus, since we observed no immune response in fetal liver. Instead, likely due to nutrient depletion, the fetal liver displayed metabolic adaptations, including increases in lipids containing docosahexaenoic acid, crucial for fetal brain development. Our study shows, for the first time, the integrated temporal response to pulmonary MIA across maternal and fetal organs.
Institute
University of Copenhagen
DepartmentDepartment of Biology
LaboratorySection for Computational and RNA Biology
Last NameSandelin
First NameAlbin
AddressCopenhagen University Ole Maaloes Vej 5, DK2200, Copenhagen N, Denmark
Emailalbin@binf.ku.dk
Phone+45 224 56668
Submit Date2024-03-12
Raw Data AvailableYes
Raw Data File Type(s)mzML
Analysis Type DetailLC-MS
Release Date2024-04-02
Release Version1
Albin Sandelin Albin Sandelin
https://dx.doi.org/10.21228/M8K43P
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001943
Project DOI:doi: 10.21228/M8K43P
Project Title:Pulmonary maternal immune activation does not extend through the placenta but leads to fetal metabolic adaptation
Project Summary:Maternal immune system activation (MIA) during pregnancy can disrupt the fetal environment, causing postnatal susceptibility to disorders. How the placenta and the fetus respond to acute MIA over time is unknown. Here, we characterized the response to acute maternal pulmonary inflammation across time in maternal and fetal organs using multi-omics. Unlike maternal organs which mounted strong innate immune responses, the placenta upregulated tissue-integrity genes, likely to prevent fetal exposure to infections, and downregulated growth-associated genes. Subsequently, the placenta upregulated biosynthesis and endoplasmic reticulum stress genes in order to return to homeostasis. These responses likely protected the fetus, since we observed no immune response in fetal liver. Instead, likely due to nutrient depletion, the fetal liver displayed metabolic adaptations, including increases in lipids containing docosahexaenoic acid, crucial for fetal brain development. Our study shows, for the first time, the integrated temporal response to pulmonary MIA across maternal and fetal organs. The study contains data from three different sources: Maternal liver samples, Fetal liver and Maternal blood.
Institute:University of Copenhagen
Department:Department of Biology
Laboratory:Section for Computational and RNA Biology
Last Name:Sandelin
First Name:Albin
Address:Copenhagen University Ole Maaloes Vej 5, DK2200, Copenhagen N, Denmark
Email:albin@binf.ku.dk
Phone:+45 224 56668

Subject:

Subject ID:SU003247
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090

Factors:

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

mb_sample_id local_sample_id Sample source exposure timepoint
SA339111Blank02Blank - -
SA339112Blank01Blank - -
SA339113Blank03Blank - -
SA339132P5MBlood ctl 12
SA339133P73MBlood ctl 12
SA339134P97MBlood ctl 12
SA339135P23MBlood ctl 12
SA339136P63MBlood ctl 12
SA339137P13MBlood ctl 12
SA339138P75MBlood ctl 12
SA339139P43MBlood ctl 12
SA339140P93MBlood ctl 2
SA339141P1MBlood ctl 2
SA339142P59MBlood ctl 2
SA339143P51MBlood ctl 2
SA339144P65MBlood ctl 24
SA339145P57MBlood ctl 24
SA339146P81MBlood ctl 24
SA339147P45MBlood ctl 24
SA339148P15MBlood ctl 24
SA339149P70MBlood ctl 24
SA339150P53MBlood ctl 5
SA339151P29MBlood ctl 5
SA339152P39MBlood ctl 5
SA339153P24MBlood lps 12
SA339154P14MBlood lps 12
SA339155P76MBlood lps 12
SA339156P6MBlood lps 12
SA339157P64MBlood lps 12
SA339158P44MBlood lps 12
SA339159P2MBlood lps 2
SA339160P38MBlood lps 2
SA339161P20MBlood lps 2
SA339162P52MBlood lps 2
SA339163P66MBlood lps 24
SA339164P34MBlood lps 24
SA339165P16MBlood lps 24
SA339166P8MBlood lps 24
SA339167P47MBlood lps 24
SA339168P58MBlood lps 24
SA339169P83MBlood lps 24
SA339170P82MBlood lps 24
SA339171P74MBlood lps 24
SA339172P84MBlood lps 24
SA339173P68MBlood lps 5
SA339174P22MBlood lps 5
SA339175P54MBlood lps 5
SA339114QC11MBlood - -
SA339115QC01MBlood - -
SA339116QC12MBlood - -
SA339117QC13MBlood - -
SA339118QC14MBlood - -
SA339119QC10MBlood - -
SA339120QC02MBlood - -
SA339121QC07MBlood - -
SA339122QC08MBlood - -
SA339123QC09MBlood - -
SA339124QC06MBlood - -
SA339125QC05MBlood - -
SA339126QC03MBlood - -
SA339127QC04MBlood - -
SA339128QC16MBlood - -
SA339129QC15MBlood - -
SA339130QC17MBlood - -
SA339131QC18MBlood - -
Showing results 1 to 65 of 65

Collection:

Collection ID:CO003240
Collection Summary:At 2, 5, 12 and 24h, dams were terminally anesthetized by subcutaneous injection of 0.2 ml of Zoletil mixture (tiletamin/zolazepam, xylazin og fentanyl) and killed by exanguination by withdrawal of heart blood into Eppendorf tubes containing 36 ml K2EDTA (N=7-9 per exposure/time point). The uterus was excised and opened. Fetuses were excised from their embryonic sac, their viability confirmed, killed by decapitation, sexed by visual inspection, and their position in the uterus noted. From each litter, the first female fetus encountered in the right uterine horn, counting from the cervix, was selected and saved for analyses. The placenta was dissected into chorion (chorionic plate, labyrinth and junctional zones) and decidua by blunt/stump dissection under stereomicroscope (Wild Heerbrugg, Switzerland)76. From dams, the liver and right lung were dissected. Dissected organs were snap frozen in liquid nitrogen and kept at -80ºC
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR003256
Treatment Summary:Lipopolysaccharide (LPS; E. Coli serotype 00:55 B5 LPS (Sigma Lot nr. 025M4040V)) was diluted to the final concentration (0.02 µg/µl) in double distilled pyrogen-free water (Chem-Lab, Zedelgem, Belgium). In the morning of GD 17, the pregnant mice were semi-randomized into control and LPS treatment groups (denoted Ctrl and LPS, respectively), evenly distributing weights among the groups. Out of 80 mice in total, 74 were pregnant. Animals were placed in a whole-body inhalation chamber with an attached anaesthetic vaporizer (Penlon Sigma Delta, Abingdon, UK), delivering 3-4% isoflurane in filtered air, and were intratracheally instilled with 50 µl of vehicle (Ctrl) or 1 μg LPS in 50 µl vehicle, followed by 200μl of air. Vehicle and LPS were administered through a 0.58 mm polyethylene tube (Ref: 427411, Becton Dickinson, Brøndby, Denmark) attached to a plastic syringe. The procedure has been shown not to affect gestation, offspring viability nor growth75. After instillation, animals were returned to their cage, briefly placed on heating pads and checked upon regularly until euthanization

Sample Preparation:

Sampleprep ID:SP003254
Sampleprep Summary:plash mix (Merck) was added to the extraction solvent and tissue samples. After centrifugation and phase separation, the apolar and polar phases were transferred to separate tubes, and the apolar phase dried under N2. *Folch, J., Lees, M. & Sloane Stanley, G. H. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem. 226, 497–509 (1957).

Combined analysis:

Analysis ID AN005133 AN005134
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Thermo Vanquish Thermo Vanquish
Column Waters ACQUITY UPLC CSH C18 (100 x 2.1mm,1.7um) Waters ACQUITY UPLC CSH C18 (100 x 2.1mm,1.7um)
MS Type ESI ESI
MS instrument type QTOF QTOF
MS instrument name Bruker Tims TOF flex Bruker Tims TOF flex
Ion Mode POSITIVE NEGATIVE
Units Peak intensity Peak intensity

Chromatography:

Chromatography ID:CH003884
Chromatography Summary:Reverse phase (C18), 10 min
Instrument Name:Thermo Vanquish
Column Name:Waters ACQUITY UPLC CSH C18 (100 x 2.1mm,1.7um)
Column Temperature:55
Flow Gradient:from 0 to 0.5 min, 40–43% B; from 0.5 to 0.7 min, 43‐65% B; from 0.7 to 0.8 min, 65-70% B; from 0.8 to 2.3 min, 70-99% B; from 2.3 to 6 min, 99% B; from 6-6.8 min, 99-40% B; from 6.8-7 min before equilibration for 3 min with the initial conditions
Flow Rate:0.4 ml/min
Solvent A:Acetonitrile/water (60:40); 10 mM ammonium formate; 0.1% formic acid
Solvent B:Isopropanol/acetonitrile (90:10); 10 mM ammonium formate; 0.1% formic acid
Chromatography Type:Reversed phase

MS:

MS ID:MS004869
Analysis ID:AN005133
Instrument Name:Bruker Tims TOF flex
Instrument Type:QTOF
MS Type:ESI
MS Comments:Data was acquired with Trapped ion mobility spectrometry (TIMS) activated. Bruker Metaboscape software was used for data processing. Annotatation was done using the built in "lipid search" module and Lipid blast.
Ion Mode:POSITIVE
  
MS ID:MS004870
Analysis ID:AN005134
Instrument Name:Bruker Tims TOF flex
Instrument Type:QTOF
MS Type:ESI
MS Comments:Data was acquired with Trapped ion mobility spectrometry (TIMS) activated. Bruker Metaboscape software was used for data processing. Annotatation was done using the built in "lipid search" module and Lipid blast.
Ion Mode:NEGATIVE
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