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.

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	ST003211
Study Title	Fetal growth delay caused by loss of non-canonical imprinting is resolved late in pregnancy and culminates in offspring overgrowth
Study 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
Submit Date	2024-05-15
Raw Data Available	Yes
Raw Data File Type(s)	mzXML
Analysis Type Detail	GC-MS
Release Date	2024-05-22
Release Version	1

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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.

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.