Placental caspase-3 expression in preeclampsia: a systematic review of observational evidence

Preeclampsia is a pregnancy disorder that contributes substantially to maternal and fetal morbidity and mortality worldwide. Apoptosis has been implicated in its pathogenesis, particularly in placental dysfunction. Caspase-3, an executioner caspase, mediates the final stage of apoptotic signaling; however, its role in preeclampsia remains incompletely defined. This systematic review evaluated observational evidence on placental caspase-3 expression in preeclampsia. PubMed, Scopus, and ScienceDirect were systematically searched on June 21, 2024. Eligible studies were human observational studies that assessed caspase-3 expression in placental tissue from pregnancies complicated by preeclampsia. Risk of bias was evaluated using the Newcastle-Ottawa Scale and the Risk of Bias Assessment Tool for Nonrandomized Studies 2.0 (RoBANS 2.0; COMPANY, CITY, STATE, COUNTRY). Data were synthesized qualitatively because of substantial methodological heterogeneity. Twelve studies (n=736 pregnancies) were included. All assessed caspase-3 expression in placental tissue obtained after delivery. Most reported higher caspase-3 expression in preeclamptic placentas than in normotensive controls, particularly in early-onset and severe preeclampsia. However, the studies varied substantially in diagnostic subtypes, measurement methods (including immunohistochemistry scoring systems, Western blotting, and enzyme-linked immunosorbent assay), and control of confounding variables. Observational evidence consistently indicates increased placental caspase-3 expression in preeclampsia, supporting enhanced apoptotic activity in affected placentas. However, because measurements were performed after delivery and caspase-3 is a downstream executioner caspase, current evidence supports its use as a marker of established placental injury. Further mechanistic and longitudinal studies are needed.