AUTHOR=Xu Xiaofeng , Wang Jing , Zhu Damin , Yin Jiaqian , Liu Jinxian , Wu Xiao , Yang Wenjuan , Hu Qian , Ren Yu , Zhang Zhiguo , Zhou Ping , Wei Zhaolian , Zou Huijuan , Cao Yunxia TITLE=Low-dose aspirin protects unexplained recurrent spontaneous abortion via downregulation of HMGB1 inflammation activation JOURNAL=Frontiers in Endocrinology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.914030 DOI=10.3389/fendo.2022.914030 ISSN=1664-2392 ABSTRACT=Background

High mobility group box protein 1 (HMGB1) is considered as a kind of sterile inflammatory mediators, which is an overexpression in patients with unexplained recurrent spontaneous abortion (URSA). Specific targeting effect of aspirin on HMGB1 has been revealed. Our previous studies have explored the application of HMGB1 as a therapeutic target of aspirin in URSA disease of mice model and human, but the dynamic process of aspirin downregulating HMGB1 concentration has not been demonstrated.

Methods

From December 2018 to November 2020, women with URSA (n = 91) and control women (n = 90) with no history of recurrent abortion or adverse pregnancy were included in the Reproductive Medicine Center of the First Affiliated Hospital of Anhui Medical University. ELISA was applied to detect the concentrations of HMGB1 and IFN-γ in the peripheral blood. Thirty-one URSA patients were monitored for low-dose aspirin treatment (2 and 4 weeks), the changes of HMGB1 and IFN-γ concentrations in peripheral blood of URSA patients before and after using aspirin were compared, and pregnancy outcomes after aspirin treatment were followed up.

Results

The levels of HMGB1 in peripheral blood were significantly higher in URSA patients compared with controls, decreasing trends of HMGB1 and IFN-γ concentrations in plasma of URSA patients were observed after treatment with low-dose aspirin continuously, and the expression of HMGB1 was positively correlated with IFN-γ. There were no birth abnormalities in the babies of the URSA patients treated with aspirin.

Conclusions

High levels of HMGB1 may be one of the pathogenesis of URSA. Low-dose aspirin may provide protective effect on the HMGB1-triggered URSA.