多囊卵巢综合征伴不明原因复发性流产患者外周血免疫调节基因表达谱的差异分析

目的从基因表达水平探讨多囊卵巢综合征(PCOS)发生不明原因反复自然流产的免疫调节机制。方法选择于我院就诊、按照鹿特丹标准诊断为PCOS,并发生2次或2次以上不明原因复发性流产的3例研究对象为病例组;同期就诊的月经规律、无异常妊娠史并已正常生育女性3例为对照组。提取2组样本的RNA进行免疫调节基因差异表达测序,并使用流式细胞术对2组的B细胞、T细胞及NK细胞及其亚型进行检测,对差异表达基因进行聚类分析及筛选统计,探讨可能参与致病机制的信号通路。结果共筛选出差异表达基因1 689个,通过GO富集分析,结合淋巴细胞亚群分析结果,筛选出14个免疫细胞功能相关的聚类;存在显著差异表达的基因主要富集在7个免疫调节功能相关的KEGG信号通路中。结论 PCOS患者存在免疫调节基因表达差异,可能通过调节NF-?B信号传导途径和B、T细胞受体信号通路导致复发性流产的发生。

Differential expression profile analysis of immunoregulation gene in patients with polycystic ovary syndrome and unexplained recurrent spontaneous abortion

This study was performed to investigate the immune regulation mechanism of unexplained recurrent spontaneous abortion(RSA) in the patients with polycystic ovary syndrome(PCOS) at gene expression level. We selected 3 in-treatment patients from our hospital who were diagnosed as PCOS according to Rotterdam criteria and suffered with two or more spontaneous abortions as case group. Meanwhile, 3 cases of normal pregnant women with regular menstruation, no abnormal pregnancy history were selected as control group. RNA was extracted from the samples of the two groups to perform sequencing of differential expressed immunoregulatory genes. Furthermore, B lymphocyte, T lymphocyte and nature killer cell were measured with flow cytometry. Gene ontology analysis and statistics filtering were performed to investigate the potential pathways that may be involved in pathogenic mechanisms. Data showed that a total of 1689 differentially expressed genes were screened out. Through gene ontology analysis and lymphocyte subset analysis, 14 immune cell function-related clusters were selected and genes with significant differential expression were mainly enriched in 7 immune regulatory functionsrelated KEGG signaling pathway. In conclusion,differential immunoregulation gene expression probably play an important role in the occurrence of recurrent spontaneous abortion via NF kappa B signaling pathway, B cell receptor signaling pathway, and T cell receptor signaling pathway in PCOS patients.