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DNA methylation profiles in preeclampsia and healthy control placentas

Abstract

Preeclampsia is a hypertensive disorder of pregnancy that affects 3-5% of all pregnancies. There is evidence to suggest that epigenetic mechanisms, such as DNA methylation, play a role in placental development and function. This study compared DNA methylation profiles of placentas from preeclampsia-affected pregnancies with placentas from healthy pregnancies to identify gene-specific changes in DNA methylation that may contribute to the development of preeclampsia. The methylation status of eight placental biopsies taken from preeclampsia-affected and 16 healthy pregnancies was analyzed using the Illumina Infinium Methylation 450 BeadChip array. Bisulfite pyrosequencing was used to confirm regions found to be differentially methylated between preeclampsia and healthy placentas. A total of 303 differentially methylated regions, 214 hypermethylated and 89 hypomethylated, between preeclampsia cases and controls were identified, after adjusting for gestational age (adjusted P < 0.05). Functional annotation found cell adhesion, wingless type MMTV Integration Site family member 2 (Wnt) signaling pathway, and regulation of transcription were significantly enriched in these gene regions. Hypermethylation of WNT2, sperm equatorial segment protein (SPESP1), NADPH oxidase 5 (NOX5), and activated leukocyte cell adhesion molecule (ALCAM) in preeclampsia placentas was confirmed with pyrosequencing. This study found differences in methylation in gene regions involved in cell signaling (WNT2), fertilization and implantation (SPESP1), reactive oxygen species signaling (NOX5), and cell adhesion (ALCAM). These results build on recently published studies that have reported significant differences in DNA methylation in preeclampsia placentas.

Type Journal
ISBN 1522-1539 (Electronic) 0363-6135 (Linking)
Authors Yeung, K. R.; Chiu, C. L.; Pidsley, R.; Makris, A.; Hennessy, A.; Lind, J. M.;
Publisher Name AM J PHYSIOL-HEART C
Published Date 2016-01-01 00:00:00
Published Volume 310
Published Issue 10
Published Pages H1295-303
URL http://www.ncbi.nlm.nih.gov/pubmed/26968548
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?13913_13733/2016-Yeung-Am J Physiol Heart Circ Physiol.pdf