Summary of Study ST003129

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 IDST003129
Study TitlePulmonary maternal immune activation does not extend through the placenta but leads to fetal metabolic adaptation - Maternal liver
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 Date2024-03-11
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:SU003246
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
SA339039Blank01Blank - -
SA339040Blank02Blank - -
SA33904163Maternal_liver ctr 12
SA33904231Maternal_liver ctr 12
SA33904343Maternal_liver ctr 12
SA33904455Maternal_liver ctr 12
SA33904513Maternal_liver ctr 12
SA33904623Maternal_liver ctr 12
SA3390475Maternal_liver ctr 12
SA33904827Maternal_liver ctr 2
SA33904951Maternal_liver ctr 2
SA3390509Maternal_liver ctr 2
SA33905119Maternal_liver ctr 2
SA33905259Maternal_liver ctr 2
SA33905393Maternal_liver ctr 2
SA33905437Maternal_liver ctr 2
SA3390557Maternal_liver ctr 24
SA33905633Maternal_liver ctr 24
SA33905765Maternal_liver ctr 24
SA33905825Maternal_liver ctr 24
SA33905915Maternal_liver ctr 24
SA33906057Maternal_liver ctr 24
SA33906145Maternal_liver ctr 24
SA3390623Maternal_liver ctr 5
SA33906339Maternal_liver ctr 5
SA33906453Maternal_liver ctr 5
SA33906511Maternal_liver ctr 5
SA33906679Maternal_liver ctr 5
SA33906721Maternal_liver ctr 5
SA33906829Maternal_liver ctr 5
SA33906976Maternal_liver lps 12
SA33907072Maternal_liver lps 12
SA33907156Maternal_liver lps 12
SA33907232Maternal_liver lps 12
SA3390736Maternal_liver lps 12
SA33907424Maternal_liver lps 12
SA33907544Maternal_liver lps 12
SA33907694Maternal_liver lps 2
SA33907720Maternal_liver lps 2
SA33907860Maternal_liver lps 2
SA3390792Maternal_liver lps 2
SA33908028Maternal_liver lps 2
SA33908110Maternal_liver lps 2
SA33908238Maternal_liver lps 2
SA33908347Maternal_liver lps 24
SA33908482Maternal_liver lps 24
SA33908584Maternal_liver lps 24
SA33908658Maternal_liver lps 24
SA33908771Maternal_liver lps 24
SA33908866Maternal_liver lps 24
SA33908934Maternal_liver lps 24
SA33909080Maternal_liver lps 5
SA33909177Maternal_liver lps 5
SA33909268Maternal_liver lps 5
SA3390934Maternal_liver lps 5
SA33909412Maternal_liver lps 5
SA33909530Maternal_liver lps 5
SA33909662Maternal_liver lps 5
SA339097QC11QC - -
SA339098QC10QC - -
SA339099QC12QC - -
SA339100QC13QC - -
SA339101QC14QC - -
SA339102QC09QC - -
SA339103QC03QC - -
SA339104QC02QC - -
SA339105QC01QC - -
SA339106QC04QC - -
SA339107QC05QC - -
SA339108QC07QC - -
SA339109QC06QC - -
SA339110QC08QC - -
Showing results 1 to 72 of 72

Collection:

Collection ID:CO003239
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:Liver

Treatment:

Treatment ID:TR003255
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:SP003253
Sampleprep Summary:Lipids were extracted from fetal liver samples (20 mg) using Folch extraction* with 8-12 replicates from each experimental group at each time point. Prior to tissue lysis, Splash mix (Merck) was added to the extraction solvent and tissue samples were lysed by beat beating in a FastPrep-24 homogenizer. 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 AN005131 AN005132
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:CH003883
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:MS004867
Analysis ID:AN005131
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:MS004868
Analysis ID:AN005132
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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