Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Department of Obstetrics and Gynecology, The Second Xiangya Hospital of Central South University, Changsha, China.
Front Immunol. 2022 Sep 23;13:902096. doi: 10.3389/fimmu.2022.902096. eCollection 2022.
The placental inflammatory processes induced maternally result in preterm birth (PTB). Serum amyloid A (SAA) is a well-known biomarker of inflammation. The objective of this study was to investigate whether murine placental SAA isoforms (SAA1-4) participate in the mechanism of spontaneous PTB and whether maternal regulation of SAA production may serve as a therapeutic approach. During the gestation, all isoforms of SAA were detectable except SAA2. The mouse model of intrauterine inflammation was established using LPS infusion to the uterus. Following intrauterine inflammation, placental SAA2 increased significantly. Inhibition of , using si, markedly decreased PTB. The increased placental expression of pro-inflammatory cytokines , , and were downregulated by si treatment. Maternal inhibition of did not change the expression of in the fetal brain. Explant inflammatory culture of placentas with si showed similar results to our experiments. This study demonstrates the highly expressed placental SAA2 as a novel therapeutic target, and maternal administration of siRNA as a promising approach to alleviate PTB.
胎盘炎症过程由母体引起，导致早产（PTB）。血清淀粉样蛋白 A（SAA）是炎症的已知生物标志物。本研究旨在探讨鼠胎盘 SAA 同工型（SAA1-4）是否参与自发性 PTB 的机制，以及母体 SAA 产生的调节是否可以作为一种治疗方法。在妊娠期间，除 SAA2 外，所有同工型均可检测到。使用 LPS 输注子宫建立宫内炎症小鼠模型。宫内炎症后，胎盘 SAA2 显著增加。使用 si 抑制 ，明显降低了 PTB 的发生。si 处理下调了促炎细胞因子 的表达。母体抑制 不会改变胎儿大脑中 的表达。用 si 处理的胎盘炎症培养物的外植体炎症培养显示出与我们的 siRNA 实验类似的结果。这项研究表明，高表达的胎盘 SAA2 是一个新的治疗靶点，而母体给予 siRNA 是一种有希望的减轻 PTB 的方法。
