Histopathology and changes in CXCL9 expression levels in patients with missed miscarriage
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摘要:
目的 分析稽留流产患者绒毛组织病理及基因表达变化，探讨稽留流产的机制。 方法 选取安徽医科大学第一附属医院2020年12月—2023年2月人工流产患者参加研究，其中研究组稽留流产35例，对照组35例。通过HE染色和透射电镜观察绒毛组织的病理变化；RNA测序并通过qRT-PCR验证测序结果及CXCL9基因表达变化。 结果 研究组HE染色合体滋养细胞减少，炎细胞浸润；透视电镜结果显示, 细胞滋养层内质网扩张, 合胞滋养层线粒体数量减少；Hofbauer细胞增多。RNA测序分析得到上调最显著的基因包括KRT34 (FDR=0.008)、MRGPGR(FDR=0.048)、CUZD1(FDR=0.002)、CXCL9 (FDR＜0.001)、CD72 (FDR=0.043)、FGF14 (FDR=0.042)、TMEM176A (FDR＜0.001)、GAPT(FDR=0.026)。qRT-PCR表明KRT34、MRGPGR、CUZD1、CXCL9、CD72、FGF14、TMEM176A、GAPT基因表达均上调(P＜0.05)，而研究组CXCL9 mRNA表达(28.66±0.38)和对照组(27.46±0.75)差异有统计学意义(P＜0.001)。 结论 炎性细胞浸润及CXCL9表达上调可能在稽留流产发展中起重要作用。 Abstract:Objective To analyze the histopathological and gene expression changes of villus in patients with missed miscarriage, and explore the mechanism of missed miscarriage. Methods Patients with induced abortion from December 2020 to February 2023 from the First Affiliated Hospital of Anhui Medical University were selected to participate in the study, including 35 cases of missed abortion in the study group and 35 cases in the control group. The pathological changes of villus tissue were observed by HE staining and transmission electron microscopy, and the sequencing results and CXCL9 gene expression changes were verified by RNA sequencing and qRT-PCR. Results In the study group, the number of HE chromatozytial trophoblasts decreased and inflammatory cells infiltrated, and fluoroscopy electron microscopy showed that the endoplasmic reticulum of cytotrophoblasts expanded, the number of mitochondria in syncytial trophoblast decreased and the number of Hofbauer cells increased. The most significant up-regulated genes were KRT34 (FDR=0.008), MRGPGR (FDR=0.048), CUZD1 (FDR=0.002), CXCL9 (FDR < 0.001), CD72 (FDR=0.043), FGF14 (FDR=0.042), TMEM176A (FDR < 0.001), and GAPT (FDR=0.026). qRT-PCR showed that the expression of KRT34, MRGPGR, CUZD1, CXCL9, CD72, FGF14, TMEM176A and GAPT genes was up-regulated, and the all P < 0.05, while the mRNA expression of CXCL9 in the study group (28.66±0.38) and the control group (27.46±0.75) were significantly different (P < 0.001). Conclusion Inflammatory cell infiltration and up-regulation of CXCL9 expression may play an important role in the development of missed miscarriage. -
Key words:
- Missed miscarriage /
- First trimester /
- CXCL9
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图 1 绒毛标本的HE染色
注：A为对照组获得的正常绒毛。B、C为研究组获得的稽留流产的绒毛。光镜，×40。
Figure 1. HE staining of villous tissue specimens
图 2 透射电子显微镜下的绒毛样本
注：A为合胞体和其中含有蛋白质的吞噬体在正常绒毛中(电镜，×4 300)。B为在正常合体滋养层中发现丰富的内质网(电镜，×4 300)。C为在正常合体滋养层中发现丰富的线粒体(电镜，×4 300)。D为在细胞滋养层中，内质网扩张，细胞核变为椭圆形，常染色质严重丢失(电镜，×4 300)。E、F为高度液泡巨噬细胞与细胞滋养层基底膜紧密接触，并且发现Hofbauer细胞增加(电镜，×4 300)。
Figure 2. Villi samples observed under a transmission electron microscope
图 5 各组CXCL9 mRNA相对表达量
注：2组比较，aP＜0.001。
Figure 5. Relative expression levels of CXCL9 mRNA in each group
表 1 2组流产患者一般资料比较
Table 1. Comparison of general data between two groups of abortion patients
组别 例数 年龄(x±s，岁) 孕次[M(P25, P75)，次] 产次[M(P25, P75)，次] 孕周(x±s，周) 研究组 32.9±4.8 2(2, 3) 1(0, 1) 9.1±1.1 对照组 32.2±5.3 2(1, 3) 1(1, 1) 6.9±0.1 统计量 0.590a -1.494b -2.736b 10.050a P值 0.557 0.135 0.061 ＜0.001 注：a为t值，b为Z值。 
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