Abnormal placental development induced by repeated cesarean sections: Investigating an animal model of placenta accreta spectrum disorders.

Abstract

INTRODUCTION: Placenta accreta spectrum (PAS) is a serious condition associated with severe postpartum hemorrhage, leading to emergency hysterectomy. Research has predominantly focused on clinical diagnosis and the prevention of adverse maternal outcomes, but the underlying pathological mechanisms remain poorly understood, partly due to the limitations of animal models. METHODS: In this study, we conducted up to three cesarean sections (CS) on full-term pregnant mice, since a history of multiple CS is an independent risk factor for PAS. We evaluated pregnancy outcomes, placental development, morphology, trophoblast invasion, and angiogenesis at the maternal-fetal interface to assess the impact of repeated CS. RESULTS: Following repeated CS, the model mice displayed adverse pregnancy outcomes, including placental dysplasia, incomplete remodeling of spiral arteries, deep trophoblast invasion at the maternal-fetal interface, and reduced placental perfusion. Additionally, the mice exhibited abnormal fetal development, imbalances in angiogenic and anti-angiogenic both within the placenta and in peripheral blood. CONCLUSION: The pathological phenotypes of placenta and adverse pregnancy outcomes observed in mice with a history of three CSs closely resemble the clinical features of PAS. This model offers a valuable tool for studying the pathogenesis of PAS and could serve as a foundation for the development of early prevention strategies.