📖 ABSTRACT/OVERVIEW
Background: Preterm pre-eclampsia, characterised by placental insufficiency driven by chronic hypoxic injury, activates complex transcriptomic programmes that determine the severity of foetal compromise. RNA sequencing has transformed our understanding of placental hypoxic gene networks, yet no study has applied this methodology to placentae from Nigerian women with pre-eclampsia, despite Nigeria's high burden of pre-eclampsia-related maternal and perinatal mortality. Objectives: This study aims to perform transcriptome-wide RNA sequencing on placentae from women with preterm pre-eclampsia compared with gestational age-matched normotensive controls at Aminu Kano Teaching Hospital, identify differentially expressed genes and enriched hypoxia-responsive pathways, validate key candidates by quantitative RT-PCR and immunohistochemistry, and construct a weighted gene co-expression network to identify hub genes predicting neonatal outcome severity. Methods: Thirty placentae from preterm pre-eclamptic deliveries and twenty from normotensive preterm deliveries will be snap-frozen at delivery. Total RNA will be extracted and sequenced using Illumina NovaSeq 6000. Differential expression analysis will use DESeq2. Pathway enrichment will apply Gene Ontology and KEGG databases. Weighted gene co-expression network analysis will identify clinically relevant gene modules. Neonatal outcomes will be correlated with hub gene expression. Expected Outcomes: Transcriptomic signatures enriched for hypoxia-inducible factor target genes, angiogenic pathways, and immune tolerance dysregulation are anticipated, with novel hub genes predicting neonatal acidosis severity. Conclusion: This study will generate the first placental transcriptomic atlas from a Nigerian pre-eclampsia cohort. Keywords: placental transcriptomics, pre-eclampsia, hypoxia-inducible factor, RNA sequencing, Kano.
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