Moss Chloe G, Dilworth Mark R, Harris Lynda K, Freeman Sally, Heazell Alexander E P
Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, University of Manchester, Manchester, UK.
Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, UK.
Am J Reprod Immunol. 2025 Apr;93(4):e70077. doi: 10.1111/aji.70077.
Stillbirth affects approximately 2 million pregnancies annually and is closely linked to placental dysfunction, which may also present clinically as foetal growth restriction (FGR) or pre-eclampsia (PE). Placental dysfunction can arise from a range of insults, including the inflammatory conditions villitis of unknown aetiology (VUE) and chronic histiocytic intervillositis (CHI). Despite ample research regarding the pathophysiology of placental dysfunction, the literature surrounding placental inflammation is more limited, with no currently established treatments. In the absence of infection, placental inflammation is hypothesised to be stimulated by damage-associated molecular patterns (DAMPs), known as sterile inflammation. The NLRP3 inflammasome, a protein scaffold that unites within the cytosol of cells, is a proposed contributor. The NLRP3 inflammasome is dysregulated in numerous diseases and has shown evidence of activation through the sterile inflammatory pathway via DAMPs. Studies have demonstrated the upregulation of the NLRP3 inflammasome and its components in placentally-mediated pregnancy pathologies. However, the link between placental dysfunction seen in these disorders and the NLRP3 inflammasome is not yet firmly established. This manuscript aims to review the evidence regarding placental inflammation seen with placental dysfunction, discuss its association with the NLRP3 inflammasome, and identify potential therapeutic interventions for this pathological inflammatory response.
死产每年影响约200万例妊娠，且与胎盘功能障碍密切相关，胎盘功能障碍在临床上也可能表现为胎儿生长受限（FGR）或子痫前期（PE）。胎盘功能障碍可由一系列损伤引起，包括病因不明的绒毛炎（VUE）和慢性组织细胞绒毛间炎（CHI）等炎症性疾病。尽管对胎盘功能障碍的病理生理学进行了大量研究，但关于胎盘炎症的文献较为有限，目前尚无既定的治疗方法。在没有感染的情况下，胎盘炎症被认为是由损伤相关分子模式（DAMPs）刺激引起的，即所谓的无菌性炎症。NLRP3炎性小体是一种在细胞胞质溶胶中组装的蛋白质支架，被认为是一个促成因素。NLRP3炎性小体在多种疾病中失调，并已显示出通过DAMPs经无菌性炎症途径激活的证据。研究表明，NLRP3炎性小体及其成分在胎盘介导的妊娠病理中上调。然而，这些疾病中出现的胎盘功能障碍与NLRP3炎性小体之间的联系尚未完全确立。本文旨在综述胎盘功能障碍时胎盘炎症的相关证据，讨论其与NLRP3炎性小体的关联，并确定针对这种病理性炎症反应的潜在治疗干预措施。
