(828.4) Different human placental epigenetics changes in pregnancies affected with preeclampsia and intrauterine growth restriction

Poster Board Number: D48

Carter Norton (Brigham Young University), Joshua Holmstrom (Brigham Young University), Paul Reynolds (Brigham Young University), Tim Jenkins (Brigham Young University), Juan Arroyo (Brigham Young University)

The placenta facilitates nutrient and gas exchange between the mother and the fetus. Intrauterine growth restriction (IUGR) and preeclampsia (PE) are placental pathologies known to cause pre-term delivery and diverse disorders in neonates. Placental adversities during complicated pregnancy may cause epigenetic changes that can altered fetal development. DNA methylation is a heritable epigenetic process that can regulate important genetic mechanisms and processes critical for optimal placental and fetal development. Our objective was to determine differential placental DNA methylation from normal, PE and IUGR human patients. Placental DNA was extracted from PE, IUGR, and control patients. Extracted DNA was then bisulfite converted for DNA methylation analysis. Bisulfite-converted DNA was hybridized to Illumina’s EPIC 850K methylation array for analysis. Methylation data was SWAN normalized and significant regions were identified using USEQ’s “methylation array scanner” and “enriched region maker” applications (with a threshold of significance of an adjusted p-value lt; 0.001). UCSC’s Genome browser was used to identify potentially impacted gene promoters associated with differentially methylated regions. Additionally, Stanford’s GREAT analysis tool was used to perform a GO term analysis to find biological processes and cellular components associated with differentially methylated regions. We observed nine significantly hypomethylated regions, six for PE (including the HIST1H4L and NAPRT-1) and three for IUGR (including CRABP1). Two regions significantly hypomethylated for both PE and IGUR gene promoters. We conclude that although we identified a unique methylation profile for both PE and IUGR, the overlap that was seen with some methylation alterations between the two pathologies could explain some of the clinical similarities observed during these obstetrics complications. Our results may provide some insights into placenta cell regulatory response to developmental syndromes. Information in these cellular components and biological pathways could be useful in determining cellular level responses to complicated diseases associated with PE and IUGR.

This work was supported by a BYU Mentoring Environment Grant (JAA and TJ).