绒毛组织中FMR1、IL-10、IFNG、HLA-G的表达与早期稽留流产的相关性研究

白娇娇; 于浩天

doi:10.12435/j.issn.2095-5227.2024.124

绒毛组织中FMR1、IL-10、IFNG、HLA-G的表达与早期稽留流产的相关性研究

Correlation between expression of FMR1, IL-10, Ifng, HLA-G in villi and early missed abortion

摘要

摘要:
背景早期稽留流产是妊娠中常见的并发症，其病因尚未完全清楚，基因表达异常可能起关键作用。
目的检测早期稽留流产患者和正常人工流产者绒毛组织中FMR1、HLA-G、IFNG、IL-10 mRNA及其蛋白的表达，分析上述指标与早期稽留流产的相关性。
方法选取2022年7月 — 2023年3月于解放军总医院第八医学中心诊治的26例早期稽留流产患者为研究对象(实验组)，同期25例正常早孕人工流产妇女作为对照(对照组)。采用实时荧光定量PCR方法检测两组绒毛组织中的FMR1、HLA-G、IFNG、IL-10 mRNA表达量，免疫组化方法及蛋白免疫印迹法检测FMR1、HLA-G、IFNG、IL-10蛋白表达水平，分析两组间上述指标的差异。
结果两组年龄及基础资料差异无统计学意义(P＞0.05)。FMR1、HLA-G、IFNG、IL-10蛋白均表达于绒毛外滋养层细胞的胞质中，FMRP、IFNG在绒毛内胚外中胚层也可见。实验组与对照组绒毛组织中FMR1、HLA-G、IL-10 mRNA表达量差异无统计学意义(P＞0.05)；实验组绒毛组织中IFNG mRNA表达量低于对照组M(IQR)：0.56(0.28 ~ 1.00) vs 1.11(0.59 ~ 2.29)，P=0.011，差异有统计学意义。实验组绒毛组织中FMRP、HLA-G、IL-10蛋白表达量低于对照组M(IQR)：0.32(0.22 ~ 0.47) vs 0.64(0.52 ~ 0.81)，P=0.001；M(IQR)：0.35(0.21 ~ 0.52) vs 0.75(0.66 ~ 1.37)，P＜0.001；0.34 ± 0.17 vs 0.67 ± 0.09，P＜0.001，IFNG蛋白表达量高于对照组(0.74 ± 0.12 vs 0.33 ± 0.12，P＜0.001)，差异均有统计学意义。FMRP、HLA-G、IL-10蛋白表达降低，IFNG蛋白表达升高，可能与早期稽留流产的发生具有相关性(P＜0.05)。相关性分析发现，FMRP与IFNG呈负相关，与IL-10蛋白呈正相关；HLA-G与IL-10呈正相关，与IFNG蛋白呈负相关；IFNG与IL-10呈负相关；均有统计学意义(P＜0.05)。
结论绒毛组织中的FMR1、HLA-G、IL-10、IFNG基因表达异常可能导致胚胎发育异常，引发早期稽留流产。

Abstract:
Background Early missed abortion, a frequent complication during pregnancy, refers to the cessation of embryo development leading to demise. While the etiology is not yet fully understood, research suggests that abnormalities in gene expression may an essential role.
Objective To detect the expression of FMR1, HLA-G, IFNG, IL-10 gene mRNA and protein in villi tissues of patients with early missed abortion and normal induced abortion, and analyze the correlation between these indicators and early missed abortion.
Methods For this study, a cohort of 26 cases diagnosed with embryonic arrest at the Eighth Medical Center of Chinese PLA General Hospital from July 2022 to March 2023 were meticulously selected to constitute the experimental group. Concurrently, a group of 25 women experiencing normal early pregnancy were chosen as a comparative control group. The innovative real-time fluorescent quantitative PCR techniques were applied to quantitatively assess the relative gene expression of FMR1, HLA-G, IFNG, and IL-10 genes within the chorionic tissue samples from both groups. Furthermore, sophisticated immunohistochemistry and protein immunoblotting methods were used to evaluate the protein levels of these targeted genes.
Results There was no significant difference in age and basic data between the two groups (P>0.05). FMR1, HLA-G, IFNG and IL-10 proteins were all expressed in the cytoplasm of extravillous trophoblast cells, and FMRP and IFNG were also found in the inner embryonic ectomesoderm of villi. There was no significant difference in the expression of FMR1, HLA-G, and IL-10 mRNA in villi tissues between the experimental group and the control group (P>0.05). The expression of IFNG mRNA in the experimental group was significantly lower than that in the control group (MIQR: 0.560.28-1.00 vs 1.110.59-2.29, P=0.011). In protein expression, the FMRP (MIQR: 0.320.22-0.47 vs 0.640.52-0.81, P=0.001), HLA-G (MIQR: 0.350.21-0.52 vs 0.750.66-1.37, P<0.001), IL-10 (0.34 ± 0.17 vs 0.67 ± 0.09, P<0.001) were lower in the experimental group than those in the control group, while IFNG (MIQR: 0.74 ± 0.12 vs 0.33 ± 0.12, P<0.001) was higher than those in the control group, with significant difference. FMRP, HLA-G, IL-10 protein expression decreased, IFNG protein expression increased, which might be associated with the occurrence of early missed abortion (P < 0.05). Correlation analysis showed that FMRP was negatively correlated with IFNG and positively correlated with IL-10 protein; HLA-G was positively correlated with IL-10 and negatively correlated with IFNG protein; IFNG was negatively correlated with IL-10, and the differences were statistically significant (P<0.05).
Conclusion Abnormal expression of FMR1, HLA-G, IL-10, and IFNG genes in villous tissue may lead to abnormal embryonic development and early missed abortion.

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