Oral Concurrent Session 7 - Basic and Translational Science
76 - The Transcriptome of Hypertensive Placentas: Superimposed preeclampsia as a transcriptionally distinct condition
Saturday, January 30, 2021
11:45 AM – 12:00 PM EST
Objective: To characterize differences in placental RNA expression in pregnancies without hypertension, with chronic hypertension, and with subtypes of preeclampsia.
Study Design: We identified women in our pregnancy biorepository with hypertensive disorders affecting singleton, euploid gestations along with matched controls. Unsupervised clustering was used to determine the need for exclusion based on clinically relevant variation, leading to the exclusion of smokers and those with autoimmune disease. Subjects were grouped as: normotensive (NT), chronic hypertensive (cHTN), preterm preeclamptic with severe features (PTSF), term preeclamptic with severe features (TSF), preterm superimposed preeclamptic (PTSI), or term superimposed preeclamptic (TSI). Bulk RNA sequencing was performed on the Illumina NovaSeq S4-150 platform. Reads were aligned to the hg38 reference genome and quality controlled using standard methods. Analysis was conducted with DESeq2, calculating log2 fold changes for all hypertensive disorders relative to NT placentas. Adjusted P-values <0.05 were considered significant.
Results: 48 placentas were analyzed: 12 NT, 13 cHTN, 5 PTSF, 11 TSF, 3 PTSI, and 4 TSI. 2,290 genes had significant differences in expression between those with and without hypertensive disease (see Figure 1). The majority of significant genes were downregulated in TSI and PTSI versus NT, a finding replicated when TSI and PTSI were compared to cHTN. Conversely, most TSF and PTSF genes were upregulated compared to the NT group. Many of the upregulated genes in TSF and PTSF with the greatest adjusted P-values are known markers of abnormal placental implantation and function (e.g., PAAPA, KISS1, CLIC3), while the downregulated genes with the greatest adjusted P-value in TSI and PTSI are largely uncharacterized in pregnancy (see Figure 2).
Conclusion: Superimposed preeclampsia appears to be a state of gene suppression whereas preeclampsia with severe features is associated with abnormal upregulation of gene expression. This suggests that superimposed preeclampsia may represent a distinct entity from preeclampsia.