Placenta accreta spectrum is a severe obstetric complication associated with uterine scarring, particularly from prior cesarean births. Despite its considerable clinical sequalae, the underlying mechanisms remain unclear. Recent evidence suggests that abnormal extracellular matrix remodeling plays a pivotal role in placenta accreta spectrum pathology.

This study investigates collagen architecture and its role in placenta accreta spectrum adherence using multimodal imaging, an in vivo mouse model, and an in vitro co-culture system, aiming to identify pathophysiology of placenta accreta spectrum with implications for improved uterine repair and placenta accreta spectrum prevention.

Human placenta accreta spectrum and nonplacenta accreta spectrum specimens were analyzed using nonlinear label-free optical imaging techniques to characterize collagen architecture at the decidual-placental interface (total n=23, placenta accreta spectrum=13). A surgical mouse model of placenta accreta spectrum was used to examine collagen organization and placental adherence patterns. Additionally, an in vitro “accreta-in-a-dish” model was developed using decidualized human uterine fibroblasts, trophoblasts, and macrophages to assess extracellular matrix remodeling, wound healing, and inflammatory interactions. Live-cell imaging and electric cell-substrate impedance sensing quantified the impact of collagen deposition and inflammation on scar resistance to electric impedance and trophoblast behavior.

Disorganized fibrillar collagen deposition with disrupted border integrity was a hallmark of placenta accreta spectrum pathology, specifically at the site of adherent, compared to nonadherent placenta accreta spectrum controls in human surgical specimens. The mouse model of placenta accreta spectrum confirmed matrix disorganization at the site of abnormal placental adherence. In vitro, collagen coating enhanced wound healing, while placental-conditioned media from placenta accreta spectrum sites impaired macrophage-driven tissue repair. In vitro, trophoblasts preferentially avoided extracellular matrix-rich regions, suggesting a role for matrix composition in placental attachment and invasion. Macrophage-mediated inflammation further compromised scar resistance, indicating an inflammatory-matrix interplay that may predispose to placenta accreta spectrum.

These findings underscore the role of extracellular matrix dysregulation in placenta accreta spectrum, highlighting collagen architecture as a critical determinant of placental adherence. Collagen modulation and targeted inflammatory interventions could improve uterine scar healing and reduce placenta accreta spectrum incidence. Future research should focus on translating these mechanistic insights into diagnostic and therapeutic strategies for placenta accreta spectrum prevention and management.

(31.06 Mo)