New Insights into Atonic Postpartum Hemorrhage: Animal Model Construction Based on Placental Nanodelivery Systems

As the leading cause of maternal mortality, the pathogenesis of postpartum hemorrhage (PPH), with 60%-70% cases of uterine atony, remains unclear due to a fundamental lack of animal models for studying. Our study develops a novel placenta-targeted nanodelivery system, termed HN@DC NPs, which is formulated with DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine), DSPE-PEG2000 (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000]), and DSPE-PEG-CSA (DSPE-PEG2000-chondroitine sulfate A). This system is designed to co-deliver key inflammatory mediators-nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) agonist nigericin and high mobility group box-1 protein (HMGB1), which are identified from pregnant women with atonic PPH to establish a pathophysiologically relevant animal model. The HN@DC NPs achieve precise enrichment in placental trophoblasts and effective diffusion into decidua with good short-term biocompatibility. The pregnant rats model constructed by HN@DC NPs shows prolonged labor duration and weakened uterine smooth muscle contractility with the activation of inflammatory markers in the placental decidua. The new insight into a reproducible construction strategy of the atonic PPH animal model in this study promotes the mechanism research and clinical therapeutic development of atonic PPH.