Background: The involvement of the placenta in the pathogenesis of preeclampsia and HELLP syndrome is well established, and placental lesions are also similar in these two syndromes. Here we aimed to examine the placental transcriptome and to identify candidate biomarkers in early-onset preeclampsia and HELLP syndrome.
Methods: Placental specimens were obtained at C-sections from women with early-onset preeclampsia and HELLP syndrome, and from controls who delivered preterm or at term. After histopathological examination, fresh-frozen placental specimens were used for microarray profiling and validation by qRT-PCR. Differential expression was analysed using log-linear models while adjusting for gestational age. Gene ontology and pathway analyses were used to interpret gene expression changes. Tissue microarrays were constructed from paraffin-embedded placental specimens and immunostained.
Results: Placental gene expression was gestational age-dependent among preterm and term controls. Out of the 350 differentially expressed genes in preeclampsia and 554 genes in HELLP syndrome, 224 genes (including LEP, CGB, LHB, INHA, SIGLEC6, PAPPA2, TREM1, and FLT1) changed in the same direction (elevated or reduced) in both syndromes. Many of these encode proteins that have been implicated as biomarkers for preeclampsia. Enrichment analyses revealed similar biological processes, cellular compartments and biological pathways enriched in early-onset preeclampsia and HELLP syndrome; however, some processes and pathways (e.g., cytokine-cytokine receptor interaction) were over-represented only in HELLP syndrome.
Conclusion: High-throughput transcriptional and tissue microarray expression profiling revealed that placental transcriptomes of early-onset preeclampsia and HELLP syndrome largely overlap, underlying a potential common cause and pathophysiologic processes in these syndromes. However, gene expression changes may also suggest a more severe placental pathology and pronounced inflammatory response in HELLP syndrome than in preeclampsia.
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