多囊卵巢综合征患者卵巢颗粒细胞的基因表达与胚胎发育潜能的相关性  

Association of gene expression in ovarian granulosa cells with embryonic development potential among patients with polycystic ovary syndrome

作　　者：滕娟 王岸聪[2] 赵向宇 刘美菊[2] 武艳[2] 李琳[1] 李文 Teng Juan;Wang Ancong;Zhao Xiangyu;Liu Meiju;Wu Yan;Li Lin;Li Wen(Laboratory Medicine Center,Linyi People′s Hospital,Linyi,Shandong 276000,China;Department of Reproductive Medicine,Linyi People′s Hospital,Linyi,Shandong 276000,China)

机构地区：[1]临沂市人民医院遗传检验医学中心,临沂276002 [2]临沂市人民医院生殖医学科,临沂276002

出　　处：《中华医学遗传学杂志》2022年第12期1354-1359,共6页Chinese Journal of Medical Genetics

基　　金：山东省医药卫生科技发展计划(2017WS495);临沂市人民医院博士启动资金(2018LYBS06)。

摘　　要：目的:探讨多囊卵巢综合征(polycystic ovary syndrome,PCOS)的不孕患者卵巢颗粒细胞基因的转录表达差异与早期胚胎发育潜能的相关性。方法:选择3对年龄、体质指数、卵巢储备功能相近,并使用促性腺激素释放激素(gonadotrophin-releasing hormone,GnRH)拮抗剂治疗的PCOS不孕症患者,其中胚胎数少者为病例组(n=3),多者为对照组(n=3)。收集患者的卵巢颗粒细胞并提取总RNA,进行基因转录表达差异的显著性分析及功能富集分析。结果:与对照组相比,病例组76个基因显著上调,110个基因显著下调。与进周期日相比,对照组人绒毛膜促性腺激素(human chorionic gonadotrophin,HCG)日的雌二醇(estradiol,E 2)水平显著升高。与对照组相比,病例组KRT7基因表达显著上调,CCNYL2表达显著下调。基因本体条目富集差异表达基因发现,与染色体分离、调控细胞周期、脂肪酸代谢等相关的基因显著富集;调控细胞组装、细胞分化、负向调控细胞周期、负向调控发育、细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK)的ERK1和ERK2信号通路等相关基因表达显著下调。KEGG分析显示,与固醇激素生物合成相关的基因显著富集。结论:接受GnRH拮抗剂治疗的PCOS不孕患者卵母细胞体外正常受精数及可用胚胎数存在显著差别,可能与卵巢颗粒细胞相关基因的表达差异有关。Objective To assess the association of gene expression and development potential of early embryos derived from patients with polycystic ovary syndrome(PCOS).Methods Three pairs of infertile patients with respectively matched age,body mass index,ovarian reserve and treatment with gonadotrophin-releasing hormone(GnRH)antagonists were selected.Patients with fewer embryos were assigned as the case group(n=3),whilst the remainders were assigned as the control group(n=3).Ovarian granulosa cells from patients were collected for the extraction of total RNA and subjected to RNA sequencing.The results were subjected to differential gene expression and functional enrichment analyses.Results Compared with the control group,76 genes were up-regulated and 110 genes were down-regulated in the case group.The level of estradiol(E2)was significantly higher in the control group on the trigger day with the injection of human chorionic gonadotrophin(HCG).Compared with the control group,the KRT7 gene was most significantly up-regulated,whilst the CCNYL2 gene was most significantly down-regulated in the case group.Gene ontology(GO)entries enrichment has found those associated with chromosome segregation,cell cycle regulation,and fatty acid metabolism to be significantly enriched.The genes participating in the regulation of cell assembly,differentiation,negative regulation of cell cycle,negative regulation of development,extracellular regulated protein kinases(ERK),ERK1 and ERK2 signaling pathways to be significantly down-regulated.KEGG enrichment analysis of cell signaling pathways revealed that steroid hormone biosynthesis-related genes were enriched.Conclusion Among patients treated with GnRH antagonists,the significant difference in the number of oocytes fertilized in vitro and the number of available embryos are associated with the difference in the expression of genes of ovarian granulosa cells.

关 键 词：不孕症 多囊卵巢综合征 卵巢颗粒细胞 胚胎发育 基因表达 

分 类 号：R711.75[医药卫生—妇产科学]