ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
Caspase-3/GSDME-Mediated Trophoblast Pyroptosis and Reciprocal Macrophage Polarization Contribute to Inflammation in Early-Onset Preeclampsia.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Oxidative Stress in Pathogenesis of Preeclampsia: Mechanistic and Clinical Insights.Antioxidants (Basel, Switzerland) · 2026Review
- Remodeling the tumor immune microenvironment: mechanisms of crosstalk between regulated cell death macrophages.Frontiers in immunology · 2026Review
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Authors and funding
16 authors.
Funding
Abstract
Early-onset preeclampsia (EOPE) is associated with excessive apoptosis and inflammation, but the mechanistic link between these processes remains enigma. Here, we report elevated circulating pro-apoptotic proteins in EOPE patients at early pregnancy, along with concurrent CASP3 activation and GSDME cleavage in EOPE placentas. Using multiple trophoblast cell lines, we demonstrate that trophoblast cells, which highly express GSDME, undergo a shift from apoptosis to CASP3-dependent pyroptosis, driving inflammation. Notably, pyroptotic trophoblasts further induce pro-inflammatory macrophage polarization within placental villi organoids, establishing a feedback loop that amplifies both trophoblast pyroptosis and inflammatory responses in trophoblast organoids-macrophage assembloids. In vivo, CASP3-GSDME-mediated trophoblast pyroptosis contributes to systemic inflammation in wild-type pregnant mice but not in Gsdme
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