Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), No 81 Meishan Road, Hefei 230032, Anhui, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, No 81 Meishan Road, Hefei 230032, Anhui, China.
Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei 230022, Anhui, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei 230032, Anhui, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China.
Life Sci. 2020 Jun 1;250:117543. doi: 10.1016/j.lfs.2020.117543. Epub 2020 Mar 10.
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.
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.
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).
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.
HMGB1 已被报道在妊娠期间的生理和病理生理反应中发挥关键作用。然而，目前尚不清楚母体-胎儿界面上过度表达的 HMGB1 是否与不明原因复发性流产（URSA）有关。本研究旨在探讨 HMGB1 在 URSA 病理学中的局部作用，确定 HMGB1、其受体（RAGE/TLR2/TLR4）和重要信号分子 NF-κB p65 在母体-胎儿界面的分布和特征，以及比较 URSA 组、对照组和阿司匹林治疗组之间 HMGB1 表达的差异。
应用 H&E 染色、Western blot 分析、免疫荧光测定和免疫组织化学染色来确定 HMGB1 及其受体在母体-胎儿界面的作用。ELISA 用于检测血浆中 HMGB1 的浓度。
本研究表明，HMGB1-RAGE/TLR2/TLR4-NF-κB 通路在 URSA 组中的激活可能发生在母体-胎儿界面。URSA 组血浆中 HMGB1 浓度高于对照组。此外，低剂量阿司匹林（ASPL）可降低 URSA 患者的 HMGB1 水平。
这是首例报道表明 HMGB1 在 URSA 患者母体-胎儿界面的作用，并为 URSA 的临床治疗拓宽了视野。HMGB1-RAGE/TLR2/TLR4-NF-κB 信号通路可能在 URSA 中激活，并解释其发病机制。HMGB1 有可能成为预防和治疗 URSA 的有前途的生物标志物。
