Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Reprod Immunol. 2021 Sep;147:103360. doi: 10.1016/j.jri.2021.103360. Epub 2021 Jul 29.
Preterm birth (PTB) is considered to be one of the most frequent causes of neonatal death. Prompt and effective measures to predict adverse fetal outcome following PTB are urgently needed. Placenta macrophages are a critical immune cell population during pregnancy, phenotypically divided into M1 and M2 subsets. An established mouse model of intrauterine inflammation (IUI) was applied. Placenta (labyrinth) and corresponding fetal brain were harvested within 24 hours post injection (hpi). Flow cytometry, Western blot, real-time qPCR, and regular histology were utilized to examine the cytokines, macrophage polarization, and sex-specificity. Placental exposure to LPS led to significantly reduced labyrinth thickness compared to PBS-exposed controls as early as 3 hpi, accompanied by apoptosis and necrosis. Pro-inflammatory M1 markers, Il-1β, and iNOS, and anti-inflammatory M2 marker Il-10 increased significantly in placentas exposed to IUI. Analysis of flow cytometry revealed that fetal macrophages (Hofbauer cell, HBCs) were mostly M1-like and that maternal inter-labyrinth macrophages (MIM) were M2-like in their features in IUI. Male fetuses displayed significantly decreased M2-like features in HBCs at 3 and 6 hpi, while female fetuses showed significant increase in M2-like features in MIM at 3 and 6 hpi. Furthermore, there was a significant correlation between the frequency of HBCs and corresponding microglial marker expression at 3 and 6 hpi. Placental macrophages demonstrated sex-specific features in response to IUI. Specifically, HBCs may be a potential biomarker for fetal brain injury at preterm birth.
早产（PTB）被认为是新生儿死亡的最常见原因之一。迫切需要及时有效的措施来预测 PTB 后的不良胎儿结局。胎盘巨噬细胞是妊娠期间关键的免疫细胞群，表型上分为 M1 和 M2 亚群。应用了一种已建立的宫内炎症（IUI）小鼠模型。在注射后 24 小时内（hpi）收获胎盘（迷路）和相应的胎脑。流式细胞术、Western blot、实时 qPCR 和常规组织学用于检查细胞因子、巨噬细胞极化和性别特异性。与 PBS 暴露对照组相比，胎盘暴露于 LPS 后，早在 3 hpi 时就导致迷路厚度显著减少，同时伴有细胞凋亡和坏死。在 IUI 中，胎盘暴露于 LPS 后，促炎 M1 标志物 Il-1β 和 iNOS 以及抗炎 M2 标志物 Il-10 显著增加。流式细胞术分析显示，胎儿巨噬细胞（Hofbauer 细胞，HBC）在 IUI 中大多呈 M1 样，而母体间迷路巨噬细胞（MIM）呈 M2 样特征。雄性胎儿在 3 和 6 hpi 时 HBC 中 M2 样特征显著减少，而雌性胎儿在 3 和 6 hpi 时 MIM 中 M2 样特征显著增加。此外，在 3 和 6 hpi 时，HBC 与相应的小胶质细胞标志物的表达频率之间存在显著相关性。胎盘巨噬细胞对 IUI 表现出性别特异性特征。具体而言，HBC 可能是预测早产胎儿脑损伤的潜在生物标志物。
