Intragenic sequences in the trophectoderm harbour the greatest proportion of methylation errors in day 17 bovine conceptuses generated using assisted reproductive technologies
Files in This Item:
|Intragenic sequences in the trophectoderm harbour the greatest proportion of methylation errors in day 17 bovine conceptuses.pdf||1.7 MB||Adobe PDF||Download|
|Title:||Intragenic sequences in the trophectoderm harbour the greatest proportion of methylation errors in day 17 bovine conceptuses generated using assisted reproductive technologies||Authors:||O'Doherty, Alan M.; McGettigan, Paul A.; Irwin, Rachelle E.; Magee, David A.; Fair, Trudee; et al.||Permanent link:||http://hdl.handle.net/10197/10822||Date:||5-Jun-2018||Online since:||2019-07-01T12:57:54Z||Abstract:||Background: Assisted reproductive technologies (ART) are widely used to treat fertility issues in humans and for the production of embryos in mammalian livestock. The use of these techniques, however, is not without consequence as they are often associated with inauspicious pre- and postnatal outcomes including premature birth, intrauterine growth restriction and increased incidence of epigenetic disorders in human and large offspring syndrome in cattle. Here, global DNA methylation profiles in the trophectoderm and embryonic discs of in vitro produced (IVP), superovulation-derived (SOV) and unstimulated, synchronised control day 17 bovine conceptuses (herein referred to as AI) were interrogated using the EmbryoGENE DNA Methylation Array (EDMA). Pyrosequencing was used to validate four loci identified as differentially methylated on the array and to assess the differentially methylated regions (DMRs) of six imprinted genes in these conceptuses. The impact of embryo-production induced DNA methylation aberrations was determined using Ingenuity Pathway Analysis, shedding light on the potential functional consequences of these differences. Results: Of the total number of differentially methylated loci identified (3140) 77.3 and 22.7% were attributable to SOV and IVP, respectively. Differential methylation was most prominent at intragenic sequences within the trophectoderm of IVP and SOV-derived conceptuses, almost a third (30.8%) of the differentially methylated loci mapped to intragenic regions. Very few differentially methylated loci were detected in embryonic discs (ED); 0.16 and 4.9% of the differentially methylated loci were located in the ED of SOV-derived and IVP conceptuses, respectively. The overall effects of SOV and IVP on the direction of methylation changes were associated with increased methylation; 70.6% of the differentially methylated loci in SOV-derived conceptuses and 57.9% of the loci in IVP-derived conceptuses were more methylated compared to AI-conceptuses. Ontology analysis of probes associated with intragenic sequences suggests enrichment for terms associated with cancer, cell morphology and growth. Conclusion: By examining (1) the effects of superovulation and (2) the effects of an in vitro system (oocyte maturation, fertilisation and embryo culture) we have identified that the assisted reproduction process of superovulation alone has the largest impact on the DNA methylome of subsequent embryos.||Funding Details:||Science Foundation Ireland||metadata.dc.description.othersponsorship:||Natural Sciences and Engineering Research Council of Canada
Strategic Research Network program supporting the EmbryoGENE Network (http://emb-bioinfo.fsaa.ulaval.ca/).
|Type of material:||Journal Article||Publisher:||Springer Nature||Journal:||BMC Genomics||Volume:||19||Start page:||1||End page:||15||Copyright (published version):||2018 the Authors||Keywords:||Assisted reproduction technologies (ART); Epigenetics; DNA methylation; Embryo; Gene body; Bovine; Genomic imprinting; Reproduction; Development||DOI:||10.1186/s12864-018-4818-3||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||Agriculture and Food Science Research Collection|
Show full item record
This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. For other possible restrictions on use please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.