Animal models of the placenta accreta spectrum: current status and further perspectives

Abstract

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.

Current understanding of the pathogenesis of placenta accreta spectrum disorder with focus on mitochondrial function

“…In this review, we summarize the current understanding of the pathogenesis of PAS and discuss future research directions with a focus on mitochondrial function. First, several hypotheses regarding the pathogenesis of PAS have been proposed; PAS is a multifactorial disease, implicating uterine abnormalities and placental abnormalities [23]. Several intriguing aspects of the hypotheses about its etiopathogenesis is based on a primary defect of the decidua basalis or scar dehiscence, aberrant vascular remodeling at the maternal-fetal interface, accumulation of an abnormally invasive trophoblast cells, or a combination thereof [23,29] (Figure 1).…”

“…First, several hypotheses regarding the pathogenesis of PAS have been proposed; PAS is a multifactorial disease, implicating uterine abnormalities and placental abnormalities [23]. Several intriguing aspects of the hypotheses about its etiopathogenesis is based on a primary defect of the decidua basalis or scar dehiscence, aberrant vascular remodeling at the maternal-fetal interface, accumulation of an abnormally invasive trophoblast cells, or a combination thereof [23,29] (Figure 1). The common endpoint includes a primary morphological or functional defect of the decidua.…”

“…Placenta accreta was first published in 1937 by Irving and Hertig [21]. The term of PAS disorder includes all grades of pregnancy complications due to abnormal placental implantation [22][23][24], which can be histologically classified as placenta accreta, placenta increta, and placenta percreta [25][26][27]. In other words, PAS is defined as a spectrum of abnormal attachment of villous tissue to the uterine wall [28].…”

Exploring maternal-fetal interface with in vitro placental and trophoblastic models

“…However, the study of placental development has been stagnant due to the lack of models that can autonomously renew and differentiate, such as STB and EVT. One of the challenges is accurately reproducing the human trophoblast model of early placental development ( Ma et al, 2023 ). In 2018, Haider et al (2016) developed an organoid model with autonomous differentiation and renewal ability using purified CTB cells from early pregnancy.…”

Cyclical endometrial repair and regeneration: Molecular mechanisms, diseases, and therapeutic interventions

“…Methods available to promote endometrial repair after surgery are IUDs, intrauterine suitable balloons (ISBs), Foley catheters, hyaluronic acid hydrogels (HA gels), cross-linked HA gels, estrogens, drugs, growth factors, and amniotic membranes. [20][21][22] Some methods have shown good therapeutic results in clinical trials. However, they are difficult to adapt to different patient situations.…”