Afshar Yalda, Kashani Ligumsky Lior, Bartels Helena C, Krakow Deborah
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, the Department of Orthopaedic Surgery, and Human Genetics, David Geffen School of Medicine, and the Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California; the School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; and the Department of UCD Obstetrics and Gynaecology, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, Ireland.
Obstet Gynecol. 2025 Jun 1;145(6):611-620. doi: 10.1097/AOG.0000000000005903. Epub 2025 Apr 10.
Placenta accreta spectrum (PAS) disorders present a significant clinical challenge, characterized by abnormal placental adherence to the uterine wall secondary to uterine scarring. With the rising global cesarean delivery rates, the incidence of this iatrogenic disorder has increased, underscoring the critical need for an understanding of its pathophysiology to inform management and prevention strategies. Normal placentation depends on tightly regulated extravillous trophoblast invasion into the decidua, spiral artery remodeling, interactions with the extracellular matrix, and immune modulation. Uterine scarring disrupts this balance, creating an environment deficient in key regulatory signals required for coordinated implantation and decidualization. In PAS, the loss of inhibitory decidual cues and deficient boundary limits permits unrestrained trophoblast into the abnormal decidual environment. Dysregulated signaling, along with an inflammatory milieu in scarred tissues, exacerbates abnormal placental development. Current prenatal imaging focuses on the appearance of excessive fibrinoid deposition, extracellular matrix remodeling, and incomplete spiral artery transformation as surrogates of PAS risk stratification. Emerging single-cell RNA sequencing and proteomic profiling offer insights into biomarkers and pathways that enable targeted interventions. Preventive efforts should prioritize reducing cesarean delivery rates to limit uterine scarring. Advances in regenerative medicine and bioengineering, including extracellular matrix-modulating biomaterials, growth factor therapies, and antifibrotic interventions, hold promise for improving scar healing and reducing PAS risk. This review bridges foundational science and clinical application, emphasizing the importance of the underlying placental biology and pathophysiology to make a clinical difference in detecting, treating, and preventing PAS. Addressing drivers of abnormal placentation is critical for improving maternal and neonatal outcomes with this increasingly prevalent iatrogenic condition.
胎盘植入谱系障碍（PAS）是一项重大的临床挑战，其特征是由于子宫瘢痕形成导致胎盘异常附着于子宫壁。随着全球剖宫产率的上升，这种医源性疾病的发病率也在增加，这凸显了深入了解其病理生理学以指导管理和预防策略的迫切需求。正常的胎盘形成依赖于绒毛外滋养层细胞对蜕膜的紧密调控性侵入、螺旋动脉重塑、与细胞外基质的相互作用以及免疫调节。子宫瘢痕破坏了这种平衡，营造出一个缺乏协调植入和蜕膜化所需关键调节信号的环境。在PAS中，抑制性蜕膜信号的丧失和边界限制的不足使得滋养层细胞不受限制地进入异常的蜕膜环境。信号失调，连同瘢痕组织中的炎症环境，加剧了胎盘的异常发育。目前的产前成像主要关注过量纤维蛋白样沉积、细胞外基质重塑和不完全螺旋动脉转化的表现，以此作为PAS风险分层的替代指标。新兴的单细胞RNA测序和蛋白质组分析为能够进行靶向干预的生物标志物和信号通路提供了见解。预防措施应优先降低剖宫产率以减少子宫瘢痕形成。再生医学和生物工程的进展，包括调节细胞外基质的生物材料、生长因子疗法和抗纤维化干预措施，有望改善瘢痕愈合并降低PAS风险。这篇综述将基础科学与临床应用联系起来，强调了潜在胎盘生物学和病理生理学在检测治疗和预防PAS方面产生临床效果的重要性。应对胎盘异常形成的驱动因素对于改善这种日益普遍的医源性疾病的母婴结局至关重要。
