A mouse model of placenta accreta spectrum.

Abstract

INTRODUCTION: Placenta Accreta Spectrum (PAS) disorder is one of the leading causes of maternal morbidity and mortality due to uncontrollable hemorrhage. The greatest risk factor for development of PAS is prior uterine surgery, frequently cesarean delivery. Despite considerable clinical knowledge, animal models of PAS are lacking. To address this, we used two surgical approaches to create uterine scarring in peripartum and non-pregnant CD-1 mice. Il10mice, with a pro-inflammatory phenotype were also studied. METHODS: In peripartum mice, a hysterotomy was performed to simulate a cesarean section. The second approach utilized endometrial curettage in non-pregnant mice. Sham-operated mice served as control. Following recovery, females were mated. On gestation day 16, pregnant females were euthanized, and the uterus was excised. Tissue was fixed, sectioned, and stained with H&E or cytokeratin immunohistochemistry. The cytokeratin-positive area extending beyond the trophoblast giant cells was measured by quantitative image analysis. Disruption of the circular (inner myometrium) smooth muscle was scored semi-quantitatively. RESULTS: In surgically scarred mice, trophoblast invasion was deeper relative to control mice, regardless of surgical method. The myometrium in experimental mice showed significant disruption compared to sham controls. Results from CD-1 and Il10mice were similar, with the latter showing more severe pathology. DISCUSSION: While further refinement of surgical method is required, our data indicate that surgical uterine scarring in mice represents a promising model of PAS.