Distinct Molecular Processes In Placentae Involved In Two Major Subtypes of Preeclampsia

Purpose: Patients with preeclampsia display a spectrum of onset time and severity of clinical presentation, yet the underlying molecular bases for the early-onset and late-onset clinical subtypes are not known. Methods: Since the root cause of PE is thought to be located in the placentae, RNA-seq has been performed on 65 high-quality placenta samples, including 33 from 30 patients and 32 from 30 control subjects, to search for molecular features. Results: Two functionally distinct sets of dysregulated genes have been identified in two major subtypes: metabolism-related genes, notably transporter genes, in early-onset severe preeclampsia (EOSPE) and immune-related genes in late-onset severe preeclampsia (LOSPE), while the late-onset mild preeclampsia (LOMPE) is not to be distinguished from normal controls. A small number of dysregulated transcription factors are found to drive the widespread gene dysregulation in both EOSPE and LOSPE. Conclusion: These results suggest that EOSPE and LOSPE have different molecular mechanisms, whereas the LOMPE may have no placenta-specific causal factors.