Summary of project PR002002
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
| 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 |
Summary of all studies in project PR002002
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003211 | Fetal growth delay caused by loss of non-canonical imprinting is resolved late in pregnancy and culminates in offspring overgrowth | Mus musculus | Hudson Institute of Medical Research | MS | 2024-05-22 | 1 | 85 | Uploaded data (332.1M)* |
