Poster Presentation 40th Annual Lorne Genome Conference 2019

Changes in placental DNA methylation across early human pregnancy (#272)

Qianhui Wan 1 2 , Tanja Jankovic-Karasoulos 1 2 , Dale Christopher McAninch 1 2 , Shalem Yiner-Lee Leemaqz 1 2 3 , Stephen Martin Pederson 4 , Melanie Denise Smith 1 2 , Konstantinos Justinian Bogias 1 2 , Jimmy Breen 1 3 4 , Claire Roberts 1 2 , Tina Bianco-Miotto 2 5
  1. Adelaide Medical School, the University of Adelaide, Adelaide, SA, Australia
  2. Robinson Research Institute, Adelaide, SA, Australia
  3. South Australian Health & Medical Research Institute (SAHMRI), Adelaide, SA, Australia
  4. Bioinformatics Hub, the University of Adelaide, Adelaide, SA, Australia
  5. School of Agriculture, Food and Wine, the University of Adelaide, Adelaide, SA, Australia

Normal placental development is vital for pregnancy success. DNA methylation is important during fetal development but its role in placental development is poorly understood. To characterise the transcriptome and methylome of placentas across early gestation, we used Illumina Infinium MethylationEPIC arrays to profile DNA methylation of 96 samples (6-23+6 weeks gestation). Studies have shown that the oxygen concentration of the placenta increases at around 10 weeks’ gestation with initiation of maternal blood flow into the intervillous space. To investigate whether changes in DNA methylation coincide with maternal blood flow, we undertook analyses between groups ≤ 10 weeks’ and > 10 weeks’ gestation. We used R/Bioconductor packages to filter, normalise and identify differentially methylated probes (DMPs) and regions (DMRs). After removing failed samples and probes, we used 91 samples and 616308 probes to identify 8410 DMPs that changed after 10 week’s gestation (adjusted p values <0.01 and methylation change > 20%). 8076 DMPs increased in methylation after 10 weeks’, while 334 probes decreased. Using DMRcate, we identified 34 DMRs (Stouffer method combined p values <0.01 and methylation change > 20%) between groups with DNA methylation higher in the >10 week’s gestation group. Of these, one DMR overlapped a CpG island, 11 overlapped promoters. Gene set analysis showed that DMRs overlapped genes enriched in tumour related gene set. HIF1A and MIR101-1 were involved in oxygen pathways and DNA methylation of HIF1A and MIR101-1 significantly increased in the >10 week’s gestation group. This indicates that during the establishment of maternal blood flow and increased oxygen to the placenta, there are numerous DNA methylation changes. In summary, we have identified placental DMPs and DMRs that change around 10 weeks’ gestation. The coincident regulatory mechanisms will be further investigated.