Fetal growth delay caused by loss of non-canonical imprinting is resolved late in pregnancy and culminates in offspring overgrowth

R Oberin; S Petautschnig; EG Jarred; Z Qu; T Tsai; NA Youngson; G Pulsoni; TT Truong; D Fernando; H Bildsoe; RO Blücher; M van den Buuse; DK Gardner; NA Sims; DL Adelson; PS Western

Journal article

Fetal growth delay caused by loss of non-canonical imprinting is resolved late in pregnancy and culminates in offspring overgrowth

R Oberin, S Petautschnig, EG Jarred, Z Qu, T Tsai, NA Youngson, G Pulsoni, TT Truong, D Fernando, H Bildsoe, RO Blücher, M van den Buuse, DK Gardner, NA Sims, DL Adelson, PS Western

eLife | eLIFE SCIENCES PUBL LTD | Published : 2024

DOI: 10.7554/eLife.81875

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Abstract

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 gesta..

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University of Melbourne Researchers

Neil Youngson Author

David Gardner Author

Natalie Sims Author

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Funding Acknowledgements

We thank A/Prof John McBain for generously supporting this work. We also thank Prof. Marnie Blewitt for critical comments on the manuscript, the Hudson Institute Animal Research Platform staff for assistance with mouse care, the Monash Histology Platform for assistance with sample preparation and slide scanning, and the Monash Micro Imaging Facility and Hudson Genomics Facility for assistance and technical advice. This project used NCRIS-enabled Metabolomics Australia infrastructure at the University of Melbourne and funded through BioPlatforms Australia. We would like to thank Dr. David De Souza and Dr. Nadeem Elahee Doomun for their advice and for running the metabolomics analyses in this study. This work was supported by grants and research funds from: National Health and Medical Research Project and Ideas Grants GNT1144966 (PSW, DKG, MvdB, DLA), GNT1144887 (PSW, DKG, DLA), and GNT2021247 (PSW, DLA), Hudson Institute of Medical Research, Victorian Government's Operational Infrastructure Support Program, Australian Government Research Training Program Scholarship support to EGJ, RO, and SP, and a philanthropic donation from Associate Professor John McBain. Metabolomics Workbench is supported by NIH U2C-DK119886 and OT2-OD030544.