Summary of Study ST003211

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 PR002002. The data can be accessed directly via it's Project DOI: 10.21228/M8TR5T This work is supported by NIH grant, U2C- DK119886.

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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 IDST003211
Study TitleFetal growth delay caused by loss of non-canonical imprinting is resolved late in pregnancy and culminates in offspring overgrowth
Study SummaryGermline epigenetic programming, including genomic imprinting, substantially influences offspring development. Polycomb Repressive Complex 2 (PRC2) plays an important role in Histone 3 Lysine 27 trimethylation (H3K27me3)-dependent imprinting, loss of which leads to growth and developmental changes in mouse offspring. In this study, we show that offspring from mouse oocytes lacking the PRC2 protein Embryonic Ectoderm Development (EED) were initially developmentally delayed, characterised by low blastocyst cell counts and substantial growth delay in mid-gestation embryos. This initial developmental delay was resolved as offspring underwent accelerated fetal development and growth in late gestation resulting in offspring that were similar stage and weight to controls at birth. The accelerated development and growth in offspring from Eed-null oocytes was associated with remodelling of the placenta, which involved an increase in fetal and maternal tissue size, conspicuous expansion of the glycogen enriched cell population and delayed parturition. Despite placental remodelling and accelerated offspring fetal growth and development, placental efficiency and fetal blood glucose levels were low, and the fetal blood metabolome was unchanged. Moreover, while expression of the H3K27me3-imprinted gene and amino acid transporter Slc38a4 was increased, fetal blood levels of individual amino acids were similar to controls, indicating that placental amino acid transport was not enhanced. Genome-wide analyses identified extensive transcriptional dysregulation and DNA methylation changes in affected placentas, including a range of imprinted and non-imprinted genes. Together, while deletion of Eed in growing oocytes resulted in fetal growth and developmental delay and placental hyperplasia, our data indicate a remarkable capacity for offspring fetal growth to be normalised despite inefficient placental function and the loss of H3K27me3-dependent genomic imprinting.
Institute
Hudson Institute of Medical Research
DepartmentCentre for Reproductive Health
Last NameWestern
First NamePatrick
Address27–31 Wright Street Clayton VIC 3168
Emailpatrick.western@hudson.org.au
Phone+61 3 8572 2700
Submit Date2024-05-15
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailGC-MS
Release Date2024-05-22
Release Version1
Patrick Western Patrick Western
https://dx.doi.org/10.21228/M8TR5T
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR002002
Project DOI:doi: 10.21228/M8TR5T
Project Title:Fetal growth delay caused by loss of non-canonical imprinting is resolved late in pregnancy and culminates in offspring overgrowth
Project Type:Targeted metabolomics
Project Summary:Germline epigenetic programming, including genomic imprinting, substantially influences offspring development. Polycomb Repressive Complex 2 (PRC2) plays an important role in Histone 3 Lysine 27 trimethylation (H3K27me3)-dependent imprinting, loss of which leads to growth and developmental changes in mouse offspring. In this study, we show that offspring from mouse oocytes lacking the PRC2 protein Embryonic Ectoderm Development (EED) were initially developmentally delayed, characterised by low blastocyst cell counts and substantial growth delay in mid-gestation embryos. This initial developmental delay was resolved as offspring underwent accelerated fetal development and growth in late gestation resulting in offspring that were similar stage and weight to controls at birth. The accelerated development and growth in offspring from Eed-null oocytes was associated with remodelling of the placenta, which involved an increase in fetal and maternal tissue size, conspicuous expansion of the glycogen enriched cell population and delayed parturition. Despite placental remodelling and accelerated offspring fetal growth and development, placental efficiency and fetal blood glucose levels were low, and the fetal blood metabolome was unchanged. Moreover, while expression of the H3K27me3-imprinted gene and amino acid transporter Slc38a4 was increased, fetal blood levels of individual amino acids were similar to controls, indicating that placental amino acid transport was not enhanced. Genome-wide analyses identified extensive transcriptional dysregulation and DNA methylation changes in affected placentas, including a range of imprinted and non-imprinted genes. Together, while deletion of Eed in growing oocytes resulted in fetal growth and developmental delay and placental hyperplasia, our data indicate a remarkable capacity for offspring fetal growth to be normalised despite inefficient placental function and the loss of H3K27me3-dependent genomic imprinting.
Institute:Hudson Institute of Medical Research
Department:Centre for Reproductive Health
Last Name:Western
First Name:Patrick
Address:27–31 Wright Street Clayton VIC 3168
Email:patrick.western@hudson.org.au
Phone:+61 3 8572 2700
Publications: Ruby Oberin, Sigrid Petautschnig, Ellen G Jarred, Zhipeng Qu, Tesha Tsai, Neil A Youngson, Gabrielle Pulsoni, Thi T Truong, Dilini Fernando, Heidi Bildsoe, Rheannon O Blücher, Maarten van den Buuse, David K Gardner, Natalie A Sims, David L Adelson, Patrick S Western (2024) Fetal growth delay caused by loss of non-canonical imprinting is resolved late in pregnancy and culminates in offspring overgrowth eLife 13:e81875; https://doi.org/10.7554/eLife.81875

Subject:

Subject ID:SU003330
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 Genotype
SA3516062703cardiac blood HET
SA3516072714cardiac blood HET
SA3516082665cardiac blood HET
SA3516092645cardiac blood HET
SA3516102795cardiac blood HET
SA3516112789cardiac blood HET
SA3516122785cardiac blood HET
SA3516132730cardiac blood HET
SA3516142757cardiac blood HET
SA3516152716cardiac blood HOM
SA3516162729cardiac blood HOM
SA3516172740cardiac blood HOM
SA3516182748cardiac blood HOM
SA3516192721cardiac blood HOM
SA3516202763cardiac blood HOM
SA3516212775cardiac blood HOM
SA3516222684cardiac blood WT
SA3516232738cardiac blood WT
SA3516242732cardiac blood WT
SA3516252760cardiac blood WT
SA3516262717cardiac blood WT
SA3516272795-3fetus blood HET-het
SA3516282714-3fetus blood HET-het
SA3516292714-4fetus blood HET-het
SA3516302730-6fetus blood HET-het
SA3516312721-3fetus blood HET-het
SA3516322703-6fetus blood HET-het
SA3516332795-1fetus blood HET-het
SA3516342795-2fetus blood HET-het
SA3516352703-1fetus blood HET-het
SA3516362665-9fetus blood HET-het
SA3516372789-6fetus blood HET-het
SA3516382757-11fetus blood HET-het
SA3516392757-7fetus blood HET-het
SA3516402703-7fetus blood HET-het
SA3516412665-6fetus blood HET-het
SA3516422785-9fetus blood HET-het
SA3516432789-1fetus blood HET-het
SA3516442757-8fetus blood HET-het
SA3516452785-5fetus blood HET-het
SA3516462795-7fetus blood HET-het
SA3516472721-4fetus blood HET-hom
SA3516482748-1fetus blood HET-hom
SA3516492729-1fetus blood HET-hom
SA3516502740-1fetus blood HET-hom
SA3516512721-2fetus blood HET-hom
SA3516522748-2fetus blood HET-hom
SA3516532740-3fetus blood HET-hom
SA3516542716-1fetus blood HET-hom
SA3516552740-2fetus blood HET-hom
SA3516562775-5fetus blood HET-hom
SA3516572729-5fetus blood HET-hom
SA3516582775-2fetus blood HET-hom
SA3516592775-3fetus blood HET-hom
SA3516602729-4fetus blood HET-hom
SA3516612775-4fetus blood HET-hom
SA3516622729-6fetus blood HET-hom
SA3516632729-3fetus blood HET-hom
SA3516642763-1fetus blood HET-hom
SA3516652775-1fetus blood HET-hom
SA3516662738-5fetus blood WT-wt
SA3516672684-7fetus blood WT-wt
SA3516682684-1fetus blood WT-wt
SA3516692738-7fetus blood WT-wt
SA3516702738-1fetus blood WT-wt
SA3516712738-6fetus blood WT-wt
SA3516722684-4fetus blood WT-wt
SA3516732684-5fetus blood WT-wt
SA3516742732-9fetus blood WT-wt
SA3516752760-5fetus blood WT-wt
SA3516762760-2fetus blood WT-wt
SA3516772684-9fetus blood WT-wt
SA3516782738-3fetus blood WT-wt
SA3516792684-2fetus blood WT-wt
SA3516802760-6fetus blood WT-wt
SA3516812732-3fetus blood WT-wt
SA3516822732-6fetus blood WT-wt
SA3516832732-7fetus blood WT-wt
SA3516842760-4fetus blood WT-wt
SA3516852760-3fetus blood WT-wt
SA3516862684-3fetus blood WT-wt
SA3516872732-5fetus blood WT-wt
SA3516882684-8fetus blood WT-wt
SA3516892760-1fetus blood WT-wt
SA3516902730-2fetus blood WT-wt
Showing results 1 to 85 of 85

Collection:

Collection ID:CO003323
Collection Summary:Fetuses of mice embryo at E17.5 developmental stage were isolated from pregnant females and decapitated on ice. ~50ul blood was collected from each fetus using a pipette and transferred into tubes containing 2ul 0.5M EDTA. collected by centrifugation and frozen at -80C before metabolic analysis. Cardiac blood and serum samples were also collected from the mothers of each litter using the same approach.
Sample Type:fetus blood or cardiac blood

Treatment:

Treatment ID:TR003339
Treatment Summary:N/A

Sample Preparation:

Sampleprep ID:SP003337
Sampleprep Summary:A monophasic extraction protocol was used to extract the metabolites from the serum. To 20 µL of serum, 140 µL of chilled 6:1 MeOH/Milli-Q water containing 0.8 nmol of 13C515N valine and 0.8 nmol of 13C6 sorbitol was added. Each sample was vortexed and then incubated at 4°C for 10 min with continuous agitation (950 rpm) using an Eppendorf Thermomixer C. The samples were centrifuged at 4°C for 10 min at 12700 rpm using an Eppendorf centrifuge 5430 R. The supernatant was transferred into a fresh 1.5 mL Eppendorf tube and the cell debris was discarded. A 16 µL aliquot of each sample was pooled to create the pooled biological quality control (PBQC). Sixteen µL of each study sample and the PBQC were transferred into HPLC inserts and evaporated at 30 °C to complete dryness, using a CHRIST RVC 2-33 CD plus speed vacuum. To limit the amount of moisture present in the insert, 20 µL 100% methanol (LCMS grade) was added to each insert and evaporated using a speed vacuum.

Combined analysis:

Analysis ID AN005266
Analysis type MS
Chromatography type GC
Chromatography system Shimadzu GC-2030
Column Agilent DB5-MS (30m x 0.25mm, 0.25um)
MS Type EI
MS instrument type Triple quadrupole
MS instrument name Shimadzu TQ8050NX
Ion Mode POSITIVE
Units Relative abundance

Chromatography:

Chromatography ID:CH003985
Chromatography Summary:The GC-MS system used comprised of an AOC6000 autosampler, a 2030 Shimadzu gas chromatograph and a TQ8050NX triple quadrupole mass spectrometer (Shimadzu, Japan)with an electron ionisation source(-70eV). The mass spectrometer was tuned according to the manufacturer’s recommendations using tris-(perfluorobutyl)-amine (CF43). GC-MS was performed on a 30m Agilent DB-5 column with 0.25mm internal diameter column and 1µm film thickness. The injection temperature (inlet) was set at 280°C, the MS transfer line at 280°C and the ion source adjusted to 200°C. Helium was used as the carrier gas at a flow rate of 1 mL/min and argon gas was used in the collision cell to generate the MRM product ion. The analysis of the derivatised samples was performed under the following oven temperature program; 100°C start temperature, hold for 4 minutes, followed by a 10°C/min oven temperature ramp to 320°C with a following final hold for 11 minutes.
Instrument Name:Shimadzu GC-2030
Column Name:Agilent DB5-MS (30m x 0.25mm, 0.25um)
Column Temperature:100 - 320
Flow Gradient:N/A
Flow Rate:1 mL/min
Solvent A:N/A
Solvent B:N/A
Chromatography Type:GC

MS:

MS ID:MS004997
Analysis ID:AN005266
Instrument Name:Shimadzu TQ8050NX
Instrument Type:Triple quadrupole
MS Type:EI
MS Comments:The GC-MS system used comprised of an AOC6000 autosampler, a 2030 Shimadzu gas chromatograph and a TQ8050NX triple quadrupole mass spectrometer (Shimadzu, Japan)with an electron ionisation source(-70eV). The mass spectrometer was tuned according to the manufacturer’s recommendations using tris-(perfluorobutyl)-amine (CF43). GC-MS was performed on a 30m Agilent DB-5 column with 0.25mm internal diameter column and 1µm film thickness. The injection temperature (inlet) was set at 280°C, the MS transfer line at 280°C and the ion source adjusted to 200°C. Helium was used as the carrier gas at a flow rate of 1 mL/min and argon gas was used in the collision cell to generate the MRM product ion. The analysis of the derivatised samples was performed under the following oven temperature program; 100°C start temperature, hold for 4 minutes, followed by a 10°C/min oven temperature ramp to 320°C with a following final hold for 11 minutes.
Ion Mode:POSITIVE
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