High-mobility group box 1 is a driver of inflammation throughout pregnancy

A proinflammatory response driven by high-mobility group box 1 (HMGB1) is important for the success of both the early stages of pregnancy and parturition initiation. However, the tight regulation of HMGB1 within these two stages is critical, as increased HMGB1 can manifest into pregnancy-related pathologies. Although during the early stages of pregnancy HMGB1 is critical for the development and implantation of the embryo, and uterine decidualization, high levels within the uterine cavity have been linked to pregnancy failure. In addition, chronic inflammation, resultant from increased HMGB1 within the maternal circulation and gestational tissues, also increases the risk for preterm labor, preterm birth, or infant mortality. Due to the link between HMGB1 and several pregnancy pathologies, the possibility of leveraging HMGB1 as a biomarker has been assessed. However, data are limited that demonstrate how known HMGB1 inhibitors could reduce inflammation within pregnancy. Thus, further research is warranted to improve our understanding of the potential of HMGB1 as a therapeutic target to reduce inflammation within pregnancy. This review aims to describe what is understood about the role of HMGB1 that drives inflammation throughout pregnancy and highlight its potential as a biomarker and therapeutic target within this context.