Premature placental senescence in early-onset preeclampsia

Early-onset preeclampsia (EOPE) remains a leading cause of maternal and perinatal morbidity worldwide. This review synthesizes evidence that premature placental senescence, centered on syncytiotrophoblast stress and the senescence-associated secretory phenotype (SASP), provides a mechanistic framework connecting placental injury to the maternal syndrome. In EOPE, defective spiral artery remodeling (45) and repeated ischemia–reperfusion can promote oxidative damage, persistent DNA-damage responses, impaired autophagy, and durable cell-cycle arrest in trophoblast lineages. Convergent data show elevated senescence markers (p16INK4a, p21, SA- β -galactosidase, γ -H2AX), transcriptomic signatures consistent with placental SASP programs, and senescent syncytiotrophoblast secretion—PAI-1 (~4-fold) and activin A (~2-fold). The SASP can transform the placenta into a source of cytokines, antiangiogenic factors, cell-free nucleic acids, and extracellular vesicles that may bias the maternal circulation toward endothelial dysfunction. We propose a stage-based model of EOPE progression and discuss differences from late-onset disease. Senescence-linked circulating signals may support multimarker risk stratification and liquid-biopsy strategies. We emphasize that human causal evidence remains associative and the senescence model is best regarded as a testable framework complementing established immune, complement, and angiogenic models.

Epigenetics · Oxidative stress · Phenotype · Placenta · Preeclampsia · Senescence · Spiral artery · Syncytiotrophoblast · Trophoblast · Pregnancy and preeclampsia studies · Preterm Birth and Chorioamnionitis · Telomeres, Telomerase, and Senescence