Integrative bioinformatics analysis identifies placental senescence-associated signatures in early-onset preeclampsia

Early-onset preeclampsia (EOPE) is a severe hypertensive disorder of pregnancy associated with preterm delivery and maternal multi-organ dysfunction. Although placental senescence and immune dysregulation have been implicated in EOPE, the expression profile of senescence-related genes(SRGs) and their mechanistic roles in disease progression remain unclear.

Multiple placental bulk RNA-seq datasets were integrated to identify senescence-related differentially expressed genes in EOPE. Weighted gene co-expression network analysis (WGCNA) and multiple machine learning algorithms were used to identify hub genes. Single-cell RNA sequencing was further applied to define the cellular expression patterns of hub genes and characterize senescence-associated changes in EOPE. Key findings were subsequently validated in clinical placental specimens using molecular and functional experiments.

A total of 44 senescence-related differentially expressed genes were identified in EOPE placentas and were mainly enriched in cell proliferation-related pathways. LEP, ENG, MIF, and CYBB were identified as hub genes and were predominantly expressed in trophoblasts and immune cells. Single-cell analysis showed that senescence-associated activity was primarily enriched in the trophoblast lineage and further implicated LEP in syncytiotrophoblast (SCT) senescence and SCT secretory dysfunction, suggesting a role in EOPE pathogenesis.

Our findings suggest that EOPE is closely related to placental senescence. Deeper investigation of SRGs and pathways may aid early diagnosis and clarify the molecular basis of EOPE.