Skip to main content

Hypomethylation and Genetic Instability in Monosomy Blastocysts May Contribute to Decreased Implantation Potential

Wrenzycki, Christine, McCallie, Blair R., Parks, Jason C., Patton, Alyssa L., Griffin, Darren K., Schoolcraft, William B., Katz-Jaffe, Mandy G. (2016) Hypomethylation and Genetic Instability in Monosomy Blastocysts May Contribute to Decreased Implantation Potential. PLOS ONE, 11 (7). Article Number 159507. ISSN 1932-6203. (doi:10.1371/journal.pone.0159507) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:56611)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://doi.org/10.1371/journal.pone.0159507

Abstract

DNA methylation is a key epigenetic mechanism responsible for gene regulation, chromatin remodeling, and genome stability, playing a fundamental role during embryonic development. The aim of this study was to determine if these epigenetic marks are associated with chromosomal aneuploidy in human blastocysts. Surplus, cryopreserved blastocysts that were donated to research with IRB consent were chosen with varying chromosomal aneuploidies and respective implantation potential: monosomies and trisomies 7, 11, 15, 21, and 22. DNA methylation analysis was performed using the Illumina Infinium HumanMethylation450 BeadChip (~485,000 CpG sites). The methylation profiles of these human blastocysts were found to be similar across all samples, independent of chromosome constitution; however, more detailed examination identified significant hypomethylation in the chromosome involved in the monosomy. Real-time PCR was also performed to determine if downstream messenger RNA (mRNA) was affected for genes on the monosomy chromosome. Gene dysregulation was observed for monosomy blastocysts within significant regions of hypo-methylation (AVEN, CYFIP1, FAM189A1, MYO9A, ADM2, PACSIN2, PARVB, and PIWIL3) (P < 0.05). Additional analysis was performed to examine the gene expression profiles of associated methylation regulators including: DNA methyltransferases (DNMT1, DNMT3A, DNMT3B, DNMT3L), chromatin modifying regulators (CSNK1E, KDM1, PRKCA), and a post-translational modifier (PRMT5). Decreased RNA transcription was confirmed for each DNMT, and the regulators that impact DNMT activity, for only monosomy blastocysts (P < 0.05). In summary, monosomy blastocysts displayed hypomethylation for the chromosome involved in the error, as well as transcription alterations of associated developmental genes. Together, these modifications may be contributing to genetic instability and therefore be responsible for the limited implantation potential observed for full monosomy blastocysts.

Item Type: Article
DOI/Identification number: 10.1371/journal.pone.0159507
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > School of Biosciences
Depositing User: Susan Davies
Date Deposited: 26 Jul 2016 10:26 UTC
Last Modified: 25 Sep 2020 14:34 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/56611 (The current URI for this page, for reference purposes)
Griffin, Darren K.: https://orcid.org/0000-0001-7595-3226
  • Depositors only (login required):