Summary of Study ST003125

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.

Study ID	ST003125
Study Title	Pulmonary maternal immune activation does not extend through the placenta but leads to fetal metabolic adaptation - Fetal liver
Study 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.
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
Submit Date	2024-02-28
Raw Data Available	Yes
Raw Data File Type(s)	mzML
Analysis Type Detail	LC-MS
Release Date	2024-04-02
Release Version	1

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:	SU003242
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
SA338780	Blank03	Blank	-	-
SA338781	Blank01	Blank	-	-
SA338782	Blank02	Blank	-	-
SA338783	FLi55.2	Fetal liver	ctrl	12
SA338784	FLi75.3	Fetal liver	ctrl	12
SA338785	FLi13.3	Fetal liver	ctrl	12
SA338786	FLi43.3	Fetal liver	ctrl	12
SA338787	FLi75.2	Fetal liver	ctrl	12
SA338788	FLi73.2	Fetal liver	ctrl	12
SA338789	FLi63.2	Fetal liver	ctrl	12
SA338790	FLi43.2	Fetal liver	ctrl	12
SA338791	FLi23.2	Fetal liver	ctrl	12
SA338792	FLi55.3	Fetal liver	ctrl	12
SA338793	FLi31.3	Fetal liver	ctrl	12
SA338794	FLi97.2	Fetal liver	ctrl	12
SA338795	FLi5.2	Fetal liver	ctrl	12
SA338796	FLi9.3	Fetal liver	ctrl	2
SA338797	FLi37.3	Fetal liver	ctrl	2
SA338798	FLi93.3	Fetal liver	ctrl	2
SA338799	FLi59.3	Fetal liver	ctrl	2
SA338800	FLi93.2	Fetal liver	ctrl	2
SA338801	FLi9.2	Fetal liver	ctrl	2
SA338802	FLi59.2	Fetal liver	ctrl	2
SA338803	FLi45.2	Fetal liver	ctrl	24
SA338804	FLi25.3	Fetal liver	ctrl	24
SA338805	FLi81.2	Fetal liver	ctrl	24
SA338806	FLi7.3	Fetal liver	ctrl	24
SA338807	FLi33.3	Fetal liver	ctrl	24
SA338808	FLi70.3	Fetal liver	ctrl	24
SA338809	FLi15.3	Fetal liver	ctrl	24
SA338810	FLi57.2	Fetal liver	ctrl	24
SA338811	FLi45.3	Fetal liver	ctrl	24
SA338812	FLi57.3	Fetal liver	ctrl	24
SA338813	FLi33.2	Fetal liver	ctrl	24
SA338814	FLi65.2	Fetal liver	ctrl	24
SA338815	FLi70.2	Fetal liver	ctrl	24
SA338816	FLi39.3	Fetal liver	ctrl	5
SA338817	FLi53.3	Fetal liver	ctrl	5
SA338818	FLi79.3	Fetal liver	ctrl	5
SA338819	FLi3.3	Fetal liver	ctrl	5
SA338820	FLi11.3	Fetal liver	ctrl	5
SA338821	FLi29.3	Fetal liver	ctrl	5
SA338822	FLi11.2	Fetal liver	ctrl	5
SA338823	FLi29.2	Fetal liver	ctrl	5
SA338824	FLi44.3	Fetal liver	lps	12
SA338825	FLi32.3	Fetal liver	lps	12
SA338826	FLi76.3	Fetal liver	lps	12
SA338827	FLi56.3	Fetal liver	lps	12
SA338828	FLi72.3	Fetal liver	lps	12
SA338829	FLi24.3	Fetal liver	lps	12
SA338830	FLi6.3	Fetal liver	lps	12
SA338831	FLi6.2	Fetal liver	lps	12
SA338832	FLi38.3	Fetal liver	lps	2
SA338833	FLi28.3	Fetal liver	lps	2
SA338834	FLi28.2	Fetal liver	lps	2
SA338835	FLi94.2	Fetal liver	lps	2
SA338836	FLi60.3	Fetal liver	lps	2
SA338837	FLi84.2	Fetal liver	lps	24
SA338838	FLi82.3	Fetal liver	lps	24
SA338839	FLi82.2	Fetal liver	lps	24
SA338840	FLi71.2	Fetal liver	lps	24
SA338841	FLi47.2	Fetal liver	lps	24
SA338842	FLi34.2	Fetal liver	lps	24
SA338843	FLi58.2	Fetal liver	lps	24
SA338844	FLi58.3	Fetal liver	lps	24
SA338845	FLi84.3	Fetal liver	lps	24
SA338846	FLi74.3	Fetal liver	lps	24
SA338847	FLi66.3	Fetal liver	lps	24
SA338848	FLi4.2	Fetal liver	lps	5
SA338849	FLi62.2	Fetal liver	lps	5
SA338850	FLi12.2	Fetal liver	lps	5
SA338851	FLi30.3	Fetal liver	lps	5
SA338852	FLi68.3	Fetal liver	lps	5
SA338853	FLi68.2	Fetal liver	lps	5
SA338854	FLi77.2	Fetal liver	lps	5
SA338855	FLi80.2	Fetal liver	lps	5
SA338856	FLi62.3	Fetal liver	lps	5
SA338857	FLi30.2	Fetal liver	lps	5
SA338858	FLi4.3	Fetal liver	lps	5
SA338859	FLi85.2	Fetal liver	tio2	24
SA338860	FLi95.2	Fetal liver	tio2	24
SA338861	FLi95.3	Fetal liver	tio2	24
SA338862	FLi69.3	Fetal liver	tio2	24
SA338863	FLi36.2	Fetal liver	tio2	24
SA338864	FLi98.2	Fetal liver	tio2	24
SA338865	FLi35.3	Fetal liver	tio2	24
SA338866	FLi69.2	Fetal liver	tio2	24
SA338867	FLi36.3	Fetal liver	tio2	24
SA338868	QC14	QC	-	-
SA338869	QC13	QC	-	-
SA338870	QC12	QC	-	-
SA338871	QC15	QC	-	-
SA338872	QC19	QC	-	-
SA338873	QC11	QC	-	-
SA338874	QC18	QC	-	-
SA338875	QC17	QC	-	-
SA338876	QC16	QC	-	-
SA338877	QC02	QC	-	-
SA338878	QC04	QC	-	-
SA338879	QC03	QC	-	-

Showing page 1 of 2 Results: 1 2 Next Showing results 1 to 100 of 107

Collection:

Collection ID:	CO003235
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:	TR003251
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

Treatment ID:

TR003251

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:	SP003249
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).

Sampleprep ID:

SP003249

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	AN005123	AN005124
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:	CH003877
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:	60% acetonitrile/40% water; 10 mM ammonium formate; 0.1% formic acid
Solvent B:	90% isopropanol/10% acetonitrile; 10 mM ammonium formate; 0.1% formic acid
Chromatography Type:	Reversed phase

MS:

MS ID:	MS004859
Analysis ID:	AN005123
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. Annotation was done using the built in "lipid search" module and Lipid blast.
Ion Mode:	POSITIVE

MS ID:	MS004860
Analysis ID:	AN005124
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. Annotation was done using the built in "lipid search" module and Lipid blast.
Ion Mode:	NEGATIVE