To systematically characterize senescence-related molecular alterations in early-onset preeclampsia (EOPE) and identify key senescence-associated genes.
Approach:
Data Integration: Multiple placental bulk RNA-seq datasets were integrated to identify senescence-related differentially expressed genes in EOPE.
Analysis Techniques: Weighted gene co-expression network analysis (WGCNA) and machine learning algorithms were used to identify hub genes, followed by single-cell RNA sequencing to define cellular expression patterns.
Validation: Key findings were validated in clinical placental specimens using molecular and functional experiments.
Key Findings:
44 senescence-related differentially expressed genes were identified in EOPE placentas, mainly enriched in cell proliferation-related pathways.
LEP, ENG, MIF, and CYBB were identified as hub genes, predominantly expressed in trophoblasts and immune cells.
Senescence-associated activity was primarily enriched in the trophoblast lineage, implicating LEP in syncytiotrophoblast senescence and dysfunction.
Interpretation:
Limitations:
The study relies on publicly available datasets, which may introduce variability.
The analysis may not fully capture the complexity of senescence mechanisms in EOPE.
Researchers linked several pregnancy urinary biomarkers—especially plasticizer and combustion-related chemical metabolites—to small shifts in gestational age and fetal growth measures in the ECHO Cohort.
