Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.
Front Immunol. 2020 Jun 9;11:1038. doi: 10.3389/fimmu.2020.01038. eCollection 2020.
Serum amyloid A1 (SAA1) is an acute phase protein produced mainly by the liver to participate in immunomodulation in both sterile and non-sterile inflammation. However, non-hepatic tissues can also synthesize SAA1. It remains to be determined whether SAA1 synthesized locally in the placenta participates in parturition via eliciting inflammatory reactions. In this study, we investigated this issue by using human placenta and a mouse model. We found that SAA1 mRNA and protein were present in human placental villous trophoblasts, which was increased upon syncytialization as well as treatments with lipopolysaccharides (LPS), tumor necrosis factor-α (TNF-α), and cortisol. Moreover, significant increases in SAA1 abundance were observed in the placental tissue or in the maternal blood in spontaneous deliveries without infection at term and in preterm birth with histological chorioamnionitis. Serum amyloid A1 treatment significantly increased parturition-pertinent inflammatory gene expression including interleukin-1β (IL-1β), IL-8, TNF-α, and cyclooxygenase-2 (COX-2), along with increased PGF2α production in syncytiotrophoblasts. Mouse study showed that SAA1 was present in the placental junctional zone and yolk sac membrane, which was increased following intraperitoneal administration of LPS. Intraperitoneal injection of SAA1 not only induced preterm birth but also increased the abundance of IL-1β, TNF-α, and COX-2 in the mouse placenta. Conclusively, SAA1 can be synthesized in the human placenta, which is increased upon trophoblast syncytialization. Parturition is accompanied with increased SAA1 abundance in the placenta. Serum amyloid A1 may participate in parturition in the presence and absence of infection by inducing the expression of inflammatory genes in the placenta.
血清淀粉样蛋白 A1（SAA1）是一种急性期蛋白，主要由肝脏产生，参与无菌性和非无菌性炎症的免疫调节。然而，非肝脏组织也可以合成 SAA1。胎盘局部合成的 SAA1 是否通过引发炎症反应参与分娩，这仍有待确定。在这项研究中，我们使用人胎盘和小鼠模型来研究这个问题。我们发现 SAA1mRNA 和蛋白存在于人胎盘绒毛滋养层细胞中，在合胞体化以及用脂多糖（LPS）、肿瘤坏死因子-α（TNF-α）和皮质醇处理后增加。此外，在足月无感染自发性分娩和伴有组织学绒毛膜羊膜炎的早产中，胎盘组织或母血中 SAA1 丰度显著增加。血清淀粉样蛋白 A1 处理显著增加了分娩相关炎症基因的表达，包括白细胞介素-1β（IL-1β）、白细胞介素-8（IL-8）、TNF-α和环氧化酶-2（COX-2），同时增加了合体滋养层细胞中 PGF2α 的产生。小鼠研究表明，SAA1 存在于胎盘连接区和卵黄囊膜中，在腹腔内给予 LPS 后增加。腹腔内注射 SAA1 不仅诱导早产，还增加了小鼠胎盘内 IL-1β、TNF-α和 COX-2 的丰度。总之，SAA1 可以在人胎盘内合成，在滋养层细胞合胞体化后增加。分娩时胎盘中 SAA1 丰度增加。血清淀粉样蛋白 A1 可能通过在胎盘内诱导炎症基因的表达参与感染和非感染的分娩。
