Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing, China.
Laboratory Animal Center, Peking University First Hospital, Beijing, China.
Front Endocrinol (Lausanne). 2023 May 8;14:1118168. doi: 10.3389/fendo.2023.1118168. eCollection 2023.
Placenta accreta spectrum disorder (PAS) is a kind of disease of placentation defined as abnormal trophoblast invasion of part or all of the placenta into the myometrium, even penetrating the uterus. Decidual deficiency, abnormal vascular remodeling in the maternal-fetal interface, and excessive invasion by extravillous trophoblast (EVT) cells contribute to its onset. However, the mechanisms and signaling pathways underlying such phenotypes are not fully understood, partly due to the lack of suitable experimental animal models. Appropriate animal models will facilitate the comprehensive and systematic elucidation of the pathogenesis of PAS. Due to the remarkably similar functional placental villous units and hemochorial placentation to humans, the current animal models of PAS are based on mice. There are various mouse models induced by uterine surgery to simulate different phenotypes of PAS, such as excessive invasion of EVT or immune disturbance at the maternal-fetal interface, which could define the pathological mechanism of PAS from the perspective of the "soil." Additionally, genetically modified mouse models could be used to study PAS, which is helpful to exploring the pathogenesis of PAS from the perspectives of both "soil" and "seed," respectively. This review details early placental development in mice, with a focus on the approaches of PAS modeling. Additionally, the strengths, limitations and the applicability of each strategy and further perspectives are summarized to provide the theoretical foundation for researchers to select appropriate animal models for various research purposes. This will help better determine the pathogenesis of PAS and even promote possible therapy.
胎盘部位滋养细胞肿瘤谱疾病（PAS）是一种胎盘种植异常疾病，定义为异常滋养细胞侵袭部分或全部胎盘进入子宫肌层，甚至穿透子宫。蜕膜缺失、母胎界面血管重塑异常和绒毛外滋养细胞（EVT）细胞过度侵袭导致其发病。然而，这些表型的发生机制和信号通路尚未完全阐明，部分原因是缺乏合适的实验动物模型。适当的动物模型将有助于全面系统地阐明 PAS 的发病机制。由于胎盘绒毛单位的功能和血绒毛膜胎盘与人类非常相似，目前 PAS 的动物模型基于小鼠。有各种通过子宫手术诱导的小鼠模型来模拟 PAS 的不同表型，如 EVT 的过度侵袭或母胎界面的免疫紊乱，这可以从“土壤”的角度定义 PAS 的病理机制。此外，还可以使用基因修饰的小鼠模型来研究 PAS，这有助于从“土壤”和“种子”两个方面分别探讨 PAS 的发病机制。本综述详细介绍了小鼠早期胎盘发育，并重点介绍了 PAS 建模的方法。此外，还总结了每种策略的优缺点及适用性，并进一步探讨了其未来的研究方向，为研究人员选择合适的动物模型以满足各种研究目的提供了理论基础。这将有助于更好地确定 PAS 的发病机制，甚至促进可能的治疗方法。
