Cervantes Elizabeth Marie, Girard Sylvie
Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55905, USA.
Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, MN 55905, USA.
Cells. 2025 Jun 24;14(13):965. doi: 10.3390/cells14130965.
Preterm premature rupture of membranes (pPROM) is a leading cause of preterm birth (PTB) and is increasingly recognized for its association with neurodevelopmental disorders (NDDs). The disruption of fetal membrane integrity introduces potential infection and inflammation into the intrauterine environment, triggering immune responses that may affect fetal development. Placental inflammation plays a pivotal role in mediating these effects, exposing the fetus to cytokines, oxidative stress, and potential microbial insults that contribute to adverse neurodevelopmental outcomes. This review examines the current evidence of the mechanistic pathways linking pPROM-induced placental inflammation to NDDs, emphasizing the roles of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) in the inflammatory responses. We discuss how these immune activations lead to immune cell recruitment and excessive (or uncontrolled) production of inflammatory mediators, leading to an overall inflammatory imbalance that has been linked to disrupted fetal brain development in animal models. Animal models provide critical insights into how both sterile and pathogenic placental inflammation alter fetal neurodevelopment, while human studies, though limited, highlight promising biomarkers and potential therapeutic targets. This review identifies critical knowledge gaps and outlines future directions to mitigate the impact of placental inflammation on long-term infant health.
胎膜早破（pPROM）是早产（PTB）的主要原因，并且其与神经发育障碍（NDDs）的关联日益受到认可。胎膜完整性的破坏将潜在的感染和炎症引入子宫内环境，引发可能影响胎儿发育的免疫反应。胎盘炎症在介导这些影响中起关键作用，使胎儿暴露于细胞因子、氧化应激和潜在的微生物侵害中，这些因素会导致不良的神经发育结局。本综述探讨了将pPROM诱导的胎盘炎症与NDDs联系起来的机制途径的现有证据，强调了病原体相关分子模式（PAMPs）和损伤相关分子模式（DAMPs）在炎症反应中的作用。我们讨论了这些免疫激活如何导致免疫细胞募集和炎症介质的过度（或不受控制）产生，从而导致整体炎症失衡，这在动物模型中已与胎儿脑发育受损相关联。动物模型为无菌性和致病性胎盘炎症如何改变胎儿神经发育提供了关键见解，而人类研究尽管有限，但突出了有前景的生物标志物和潜在的治疗靶点。本综述确定了关键的知识空白，并概述了减轻胎盘炎症对婴儿长期健康影响的未来方向。
