AIMS HMGB1 has been reported to play a crucial role in the physiological and pathophysiological responses during pregnancy. However, it is still unknown whether excessively expressed HMGB1 at the maternal-fetal interface related to Unexplained Recurrent Spontaneous Abortion (URSA). This study was designed to investigate the local capability of HMGB1 in the pathology of URSA, determined the distributions and characteristics of HMGB1, its receptors (RAGE/TLR2/TLR4) and important signaling molecule NF-κB p65 expression at the maternal-fetal interface，as well as compared the differences of HMGB1 expression between the URSA group, control group and aspirin treatment group. MATERIAL AND METHODS H&E staining, Western blot analysis, immunofluorescence assay and immunohistochemical staining were applied to determine the effect of HMGB1 and its receptors at the maternal-fetal interface. ELISA was utilized to detect the concentration of HMGB1 in plasma. KEY FINDINGS Our study demonstrated that the activation of the HMGB1-RAGE/TLR2/TLR4-NF-κB pathway at the maternal-fetal interface may have occurred in the URSA group. HMGB1 concentration in plasma was higher in the URSA group than the control group. Furthermore, the levels of HMGB1 of subjects with URSA could be reduced by administrating low doses of aspirin (ASPL). SIGNIFICANCE This is the first report indicating the roles of HMGB1 at the maternal-fetal interface of URSA patients and broadening the horizons for clinical treatment of URSA. HMGB1-RAGE/TLR2/TLR4-NF-κB signaling pathway may be activated at the maternal-fetal interface in URSA and account for its pathogenesis. HMGB1 have the potential to be promising biomarkers in prevention and therapy of URSA.

中文翻译：

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通过增加HMGB1-RAGE / TLR2 /TLR4-NF-κB信号通路来破坏URSA患者的母胎界面。

据报道，AIMS HMGB1在妊娠期间的生理和病理生理反应中起着至关重要的作用。然而，仍然未知在与无法解释的复发性自然流产（URSA）相关的母胎界面是否过度表达HMGB1。本研究旨在调查HMGB1在URSA病理学中的局部能力，确定HMGB1的分布和特征，其受体（RAGE / TLR2 / TLR4）和重要的信号分子NF-κBp65在母胎界面的表达，并比较了URSA组，对照组和阿司匹林治疗组之间HMGB1表达的差异。材料和方法H＆E染色，蛋白质印迹分析，免疫荧光法和免疫组化染色法用于确定HMGB1及其受体在母胎界面的作用。ELISA用于检测血浆中HMGB1的浓度。主要发现我们的研究表明，URSA组可能在母胎界面激活了HMGB1-RAGE / TLR2 /TLR4-NF-κB通路。URSA组的血浆HMGB1浓度高于对照组。此外，可以通过服用低剂量的阿司匹林（ASPL）降低患有URSA的受试者的HMGB1水平。意义这是第一份表明HMGB1在URSA患者的母胎界面中的作用并拓宽了URSA临床治疗视野的报告。HMGB1-RAGE / TLR2 /TLR4-NF-κB信号通路可能在URSA的母胎界面被激活，并解释其发病机理。HMGB1有潜力成为预防和治疗URSA的有前途的生物标志物。