Transcriptomic Profiling of Placental Immune Dysregulation in Preeclampsia With and Without Severe Features Among Nigerian Women

The immunological mechanisms underpinning placental dysfunction in preeclampsia involve complex transcriptomic reprogramming of trophoblast and decidual immune cell populations, yet no transcriptomic placental characterisation of preeclampsia has been conducted in an African population whose distinct maternal immune phenotype and pathogen exposure history may generate population-specific transcriptomic signatures. This dissertation profiles the transcriptome of placental immune dysregulation in preeclampsia with and without severe features among Nigerian women. Placental samples from 30 severe preeclamptic, 30 non-severe preeclamptic, and 30 normotensive deliveries at three South West teaching hospitals (Lagos, Ogun, and Osun States) were collected within 30 minutes of delivery and processed for bulk RNA-seq using the Illumina NovaSeq 6000 platform. Differential gene expression, pathway enrichment, deconvolution of immune cell populations using CIBERSORT, and transcription factor network analysis were conducted. Severe preeclampsia placentas showed significant upregulation of complement cascade genes (C3, C5, C1QA), pro-inflammatory macrophage polarisation markers (CD64, MRC1), and HIF-1alpha target genes compared to both non-severe and normotensive placentas. Regulatory T-cell fraction was significantly depleted in severe preeclampsia by CIBERSORT deconvolution. A 48-gene preeclampsia severity transcriptomic signature discriminated severe from non-severe with AUC of 0.89. Several identified dysregulated pathways showed population-specific differential expression compared to published European preeclampsia transcriptomes, suggesting ethnicity-modified transcriptomic responses. The dissertation advances preeclampsia molecular biology with original population-specific findings. Keywords: preeclampsia, placental transcriptomics, RNA-seq, immune dysregulation, Nigeria