A Preliminary Study Of Aspirin Inhibition Of Placenta Accreta Spectrum After Uterine Trauma

【Background】Placenta accreta spectrum(PAS)is a class of diseases that extravillous trophoblasts abnormally invade into the uterus.According to the degree of overinvasion,it can be divided into three types,such as placenta accreta(PA),placenta increta(PI),and placenta percreta(PP).Obstetrical sonography in the second or third trimester of pregnancy is the mainstay of antenatal diagnosis.Or,it can be diagnosed by pathological examination of the placenta after delivery.As the specific pathological mechanism of PAS is still unclear,there is no effective and feasible scheme for early screening.For which,further studies and explorations are needed to dig for predictive molecules.In recent years,a few studies have found the abnormal distribution of NK cells and T cells in the placenta of PAS patients,suggesting that the disturbance of immune environment at the maternal-fetal interface resulted in excessive EVTs invasion.The non-steroidal anti-inflammatory drug—aspirin(ASP)has been used for the treatment of inflammation induced by various trauma years ago.Based on its antiinflammatory properties and clinical application for the prevention of preeclampsia(PE),we speculated that ASP has the feasibility of clinical intervention in PAS.【Objective】The purpose of this study was to establish a PAS model in mouse by simulating human cesarean section to explore the pro-inflammatory mechanism in PAS and the anti-inflammatory mechanism of ASP in this process.【Methods】1)Setting a PAS model by simulating human cesarean section in mouse.Pathological examinations were performed on the E14.5 placenta to determine the effects of surgery on tissue morphology,trophoblast giant cells(TGCs)overinvasion and angiogenesis.2)We set up a series of gradient concentration of ASP to determine the effect of ASP in preventing PAS,which was induced by uterine trauma in mice.3)The m RNA expression levels of immunoregulatory factors in the uterus were detected after surgery to explore the effect of surgery on the immune environment of the uterus.4)To explore the temporal and spatial changes of immune environment at the maternal-fetal interface and the regulatory role of ASP in this process,we detected the m RNA expression levels of inflammatory factors in uterus,decidua and placenta of PAS mice during the first,second and third trimester of pregnancy.【Results】1)Endometrial injury induced by surgery may disturb the normal inflammatory response and promote the m RNA expression level of the molecules in NRF2 pathway.2)ASP present the ability to promote maternal hyperangiogenesis,perivascular inflammatory cell infiltration,excessive TGCs invasion and hyperangiogenesis of the labyrinth zone(LA)in postoperative pregnancy.3)ASP can improve the immune environment disorders in uterus,decidua and placenta induced by cesarean to inhibit PAS.【Conclusion】ASP can regulate the expression of inflammatory factors at the maternal-fetal interface to improve the immune dysregulation,and finally present the ability to prevent PAS induced by cesarean.