Summary of Study ST000872

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 PR000604. The data can be accessed directly via it's Project DOI: 10.21228/M8M09W This work is supported by NIH grant, U2C- DK119886.

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Study IDST000872
Study TitleMaternal Hypoxemia and oxidative stress in the fetus, newborn, and adult. exercise training for peripheral artery disease
Study TypeDisease model
Study SummaryGestational hypoxia presents a significant stress to an unborn fetus that can lead to significant complications related to fetal growth restriction and resulting in diseases in the newborn as well as those manifesting later in life. Recent evidence indicates that inflammation and oxidative stress are contributing factors to hypoxia-related diseases. The Center for Perinatal Biology at Loma Linda University has studied gestational chronic hypoxia in a sheep model for over 20 years to study dysfunction of vascular and nonvascular tissues derived from mothers, fetuses and offspring. In this project we are attempting to use metabolomics to assess metabolic dysregulation in vascular tissues along with markers of oxidative stress and inflammation in the mother and offspring to determine the extent of dysregulation due to chronic hypoxia. Untargeted metabolomics analysis focused on sheep plasma and arteries from the lung, resistance arteries in the brain, uterine arteries, and cultured human myocytes will be used to explore markers of glucose and lipid metabolism disruption. Targeted analyses of oxylipins and endocannabinoids will be used on the same samples to explore markers of oxidative stress and inflammation, which should be increased during hypoxia. This study should delineate pathways and biomarkers that help explain how hypoxia leads to the development of neonatal as well as adult-onset diseases associated with chronic hypoxia that are inter-related with fetal growth restriction.
Institute
University of California, Davis
DepartmentUSDA Western Human Nutrition Research Center
LaboratoryNewman's Lab
Last NameNewman
First NameJohn
Address430 West Health Sciences Dr. Davis, Ca, 95616
EmailJohn.Newman@ars.usda.gov
Phone(530) 752-1009
Submit Date2017-08-29
Raw Data AvailableYes
Raw Data File Type(s)wiff
Analysis Type DetailLC-MS
Release Date2017-10-11
Release Version1
John Newman John Newman
https://dx.doi.org/10.21228/M8M09W
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000604
Project DOI:doi: 10.21228/M8M09W
Project Title:Maternal Hypoxemia and oxidative stress in the fetus, newborn, and adult.
Project Summary:Gestational hypoxia presents a significant stress to an unborn fetus that can lead to significant complications related to fetal growth restriction and resulting in diseases in the newborn as well as those manifesting later in life. Recent evidence indicates that inflammation and oxidative stress are contributing factors to hypoxia-related diseases. The Center for Perinatal Biology at Loma Linda University has studied gestational chronic hypoxia in a sheep model for over 20 years to study dysfunction of vascular and nonvascular tissues derived from mothers, fetuses and offspring. In this project we are attempting to use metabolomics to assess metabolic dysregulation in vascular tissues along with markers of oxidative stress and inflammation in the mother and offspring to determine the extent of dysregulation due to chronic hypoxia. Untargeted metabolomics analysis focused on sheep plasma and arteries from the lung, resistance arteries in the brain, uterine arteries, and cultured human myocytes will be used to explore markers of glucose and lipid metabolism disruption. Targeted analyses of oxylipins and endocannabinoids will be used on the same samples to explore markers of oxidative stress and inflammation, which should be increased during hypoxia. This study should delineate pathways and biomarkers that help explain how hypoxia leads to the development of neonatal as well as adult-onset diseases associated with chronic hypoxia that are inter-related with fetal growth restriction.
Institute:University of California, Davis
Department:Genome and Biomedical Sciences Facility
Laboratory:WCMC Metabolomics Core
Last Name:Fiehn
First Name:Oliver
Address:1315 Genome and Biomedical Sciences Facility, 451 Health Sciences Drive, Davis, CA 95616
Email:ofiehn@ucdavis.edu
Phone:(530) 754-8258
Funding Source:NIH U24DK097154

Subject:

Subject ID:SU000899
Subject Type:Sheep
Subject Species:Ovis aries
Taxonomy ID:9940
Gender:Both
Species Group:Mammal

Factors:

Subject type: Sheep; Subject species: Ovis aries (Factor headings shown in green)

mb_sample_id local_sample_id Life stage Pregnancy status Treatment group Sample origin
SA049084E08Adult Non-pregnant Hypoxic Arterial
SA049085A01Adult Non-pregnant Hypoxic Arterial
SA049086C02Adult Non-pregnant Hypoxic Arterial
SA049087C06Adult Non-pregnant Hypoxic Arterial
SA049088G07Adult Non-pregnant Hypoxic Arterial
SA049089G04Adult Non-pregnant Hypoxic Arterial
SA049090E09Adult Non-pregnant Hypoxic Arterial
SA049091H02Adult Non-pregnant Hypoxic Venous
SA049092E10Adult Non-pregnant Hypoxic Venous
SA049093F05Adult Non-pregnant Hypoxic Venous
SA049094E01Adult Non-pregnant Hypoxic Venous
SA049095H04Adult Non-pregnant Hypoxic Venous
SA049096A07Adult Non-pregnant Normoxic Arterial
SA049097A04Adult Non-pregnant Normoxic Arterial
SA049098E05Adult Non-pregnant Normoxic Venous
SA049099G09Adult Non-pregnant Normoxic Venous
SA049100E03Adult Non-pregnant Normoxic Venous
SA049101B02Adult Non-pregnant Normoxic Venous
SA049102B04Adult Non-pregnant Normoxic Venous
SA049103A10Adult Non-pregnant Normoxic Venous
SA049104B05Adult Non-pregnant Normoxic Venous
SA049105F08Adult Pregnant Hypoxic Arterial
SA049106F04Adult Pregnant Hypoxic Venous
SA049107F01Adult Pregnant Hypoxic Venous
SA049108B01Adult Pregnant Hypoxic Venous
SA049109C10Adult Pregnant Normoxic Venous
SA049110(A02 + H09) / 2Adult Pregnant Normoxic Venous
SA049111A09Adult Unknown Hypoxic Arterial
SA049112D09Adult Unknown Hypoxic Arterial
SA049113H08Adult Unknown Hypoxic Arterial
SA049114C05Adult Unknown Hypoxic Venous
SA049115D05Adult Unknown Hypoxic Venous
SA049116(D06 + H01) / 2Adult Unknown Hypoxic Venous
SA049117B07Adult Unknown Hypoxic Venous
SA049118C07Adult Unknown Hypoxic Venous
SA049119G08Adult Unknown Hypoxic Venous
SA049120E04Adult Unknown Hypoxic Venous
SA049121C03Adult Unknown Hypoxic Venous
SA049122C09Fetus - Hypoxic Arterial
SA049123C08Fetus - Hypoxic Arterial
SA049124D07Fetus - Hypoxic Arterial
SA049125E07Fetus - Hypoxic Arterial
SA049126D04Fetus - Hypoxic Arterial
SA049127(D03 + F09) / 2Fetus - Hypoxic Arterial
SA049128D08Fetus - Hypoxic Arterial
SA049129F07Fetus - Hypoxic Arterial
SA049130C04Fetus - Hypoxic Arterial
SA049131G02Fetus - Hypoxic Venous
SA049132F10Fetus - Hypoxic Venous
SA049133A05Fetus - Hypoxic Venous
SA049134A03Fetus - Hypoxic Venous
SA049135D02Fetus - Hypoxic Venous
SA049136D01Fetus - Normoxic Arterial
SA049137H05Fetus - Normoxic Arterial
SA049138F02Fetus - Normoxic Arterial
SA049139E06Fetus - Normoxic Arterial
SA049140G01Fetus - Normoxic Venous
SA049141B03Fetus - Normoxic Venous
SA049142E02Fetus - Normoxic Venous
SA049143G05Fetus - Normoxic Venous
SA049144H07Newborn - Hypoxic Venous
SA049145B09Newborn - Hypoxic Venous
SA049146A06Newborn - Hypoxic Venous
SA049147G03Newborn - Normoxic Venous
SA049148H06Newborn - Normoxic Venous
SA049149B08Newborn - Normoxic Venous
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Collection:

Collection ID:CO000893
Collection Summary:Whole blood was immediately separated by centrifugation and the plasma frozen in liquid nitrogen and stored at -80C for later analysis.
Sample Type:Blood
Blood Serum Or Plasma:Venous and arterial plasma

Treatment:

Treatment ID:TR000913
Treatment Summary:To induce chronic hypoxia, pregnant and non-pregnant ewes were transported to the White Mountain Research Station that is owned and operated by the University of California. Animals were housed at the Barcroft Research Station (3800 m) for 100+ days prior to having the pregnant or non-pregnant ewes or 2 week old newborn lambs transported back to Loma Linda for study.

Sample Preparation:

Sampleprep ID:SP000906
Sampleprep Summary:After randomization, a 50 μl plasma aliquot in a 1.5 mL polypropylene Eppendorf tube was enriched with deuterated surrogates in 10 µL methanol (Tables S1 and S2 from Agrawal, K., L.A. Hassoun, N. Foolad, T.L. Pedersen, R.K. Sivamani, J.W. Newman. 2017. Sweat lipid mediator profiling: a non-invasive approach for cutaneous research. J. Lipid Res. 58:188–195 [EPub: Nov 7, 2016]. doi: 10.1194/jlr.M071738) and 5 μl of BHT/EDTA in 1:1 methanol/water (v/v). A total of 200 μl 1-cyclohexyl uredio, 3-dodecanoic acid / 1-phenyl ureido, 3-hexanoic acid (CUDA / PUHA) in 1:1 methanol/acetonitrile (v/v) was added, the sample mixed by vortexing and protein precipitate was removed by centrifugation (10 min, 10,000 RCF, 6 °C). The supernatant was filtered by centrifugation through 1 µm PVDF membranes (Millipore, Billerica, MA) at 6 °C and 4,500 RCF for 3 min. The filtrate was stored in glass vials at -20 °C until UPLC-MS/MS analysis.

Combined analysis:

Analysis ID AN001404 AN001405
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Waters Acquity Waters Acquity
Column Aquity C18 BEH (100 x 2.1mm,1.7um) Aquity C18 BEH (100 x 2.1mm,1.7um)
MS Type ESI ESI
MS instrument type Triple quadrupole Triple quadrupole
MS instrument name ABI Sciex 6500 QTrap ABI Sciex 6500 QTrap
Ion Mode NEGATIVE POSITIVE
Units Concentration (nM) Concentration (nM)

Chromatography:

Chromatography ID:CH000984
Instrument Name:Waters Acquity
Column Name:Aquity C18 BEH (100 x 2.1mm,1.7um)
Column Temperature:60 °C
Flow Gradient:See protocol/methods file
Flow Rate:0.25 mL/min
Internal Standard:See protocol/methods file
Retention Time:See protocol/methods file
Sample Injection:5 µL
Solvent A:100% water; 0.1% acetic acid
Solvent B:90% acetonitrile/ 10% isopropanol
Analytical Time:20 min
Weak Wash Solvent Name:20% methanol, 10% isopropanol
Weak Wash Volume:600 µL
Strong Wash Solvent Name:50:50 Acetonitrile:Methanol
Strong Wash Volume:600 µL
Chromatography Type:Reversed phase

MS:

MS ID:MS001296
Analysis ID:AN001404
Instrument Name:ABI Sciex 6500 QTrap
Instrument Type:Triple quadrupole
MS Type:ESI
Ion Mode:NEGATIVE
  
MS ID:MS001297
Analysis ID:AN001405
Instrument Name:ABI Sciex 6500 QTrap
Instrument Type:Triple quadrupole
MS Type:ESI
Ion Mode:POSITIVE
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