环状RNA circSTK40调控组蛋白H3K4甲基化水平参与反复胚胎种植失败发生发展的功能和机制研究

批准号:
82101752
项目类别:
青年科学基金项目
资助金额:
20.0 万元
负责人:
倪天翔
依托单位:
学科分类:
胚胎着床、母胎互作与生殖免疫及相关疾病
结题年份:
2023
批准年份:
2021
项目状态:
已结题
项目参与者:
倪天翔
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中文摘要
反复胚胎种植失败(RIF)是指经历多次优质胚胎移植仍未获临床妊娠,子宫内膜容受性建立的机制研究是RIF病因学的热点问题,而环状RNA在该过程中的作用及联合多组学的研究鲜有报道。申请人前期研究发现在RIF患者着床期内膜组织中circSTK40显著上调,过表达后可显著抑制内膜基质细胞的蜕膜化程度和细胞凋亡、促进细胞糖酵解。进一步研究显示circSTK40可与甲基化修饰的组蛋白H3K4结合,并增加其甲基化水平,提示circSTK40可能通过调控组蛋白H3K4甲基化水平参与子宫内膜容受性的建立过程。本项目拟在前期研究基础上,通过细胞实验、内膜类器官和小鼠模型多方位探讨circSTK40、组蛋白甲基化和下游基因在内膜容受性建立和胚胎种植过程中的具体作用和分子机制,并收集胚胎移植当日的宫腔液验证circSTK40联合下游基因/蛋白作为生物学标记物的潜在价值,为RIF的预防和治疗提供理论依据和治疗靶点。
英文摘要
Recurrent implantation failure (RIF) refers to the failure to achieve clinical pregnancy after multiple transfers of high-quality embryos. Endometrial receptivity, as one of most important etiological factors, is always a hot topic in RIF research study. However, the role of circular RNAs (circRNAs) combined with multi-omics study in regulation of endometrial receptivity remains largely unknown. Our previous studies showed that circSTK40 was significantly up-regulated in midluteal-phase endometrium from RIF patients. Overexpression of circSTK40 in human endometrial stromal cell line and primary cells notably inhibited the decidualization level and cell apoptosis, while enhanced cell glycolysis process in vitro. Initial mechanism study demonstrated that circSTK40 directly bound to methylation-modified histone H3K4 and increased its methylation levels, indicating that circSTK40 may participate in regulation of endometrial receptivity through modulating the methylation levels of histone H3K4. Based on previous results, we will further investigate the effects and underlying mechanisms involved in endometrial receptivity of circSTK40, histone methylation and downstream genes/proteins from a multi-omics angle through cell experiments, endometrial organoids and mouse models. Our study will also collect uterine fluids on the exact day of embryo transfer and verify the potential value of circSTK40 and downstream genes/proteins as biomarkers, to provide new targets for the diagnosis and treatment of RIF.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
Pregnancy and neonatal outcomes after long-term vitrification of blastocysts among 6,900 patients after their last live birth
6,900 名患者上次活产后囊胚长期玻璃化冷冻后的妊娠和新生儿结局
DOI:10.1016/j.fertnstert.2022.10.016
发表时间:2023
期刊:Fertility and Sterility
影响因子:6.7
作者:Yan Yueyue;Zhang Qian;Yang Linlin;Zhou Wei;Ni Tianxiang;Yan Junhao
通讯作者:Yan Junhao
DOI:10.1002/ijgo.14862
发表时间:2023-05
期刊:International Journal of Gynecology & Obstetrics
影响因子:3.8
作者:L. Yang;T. Ni;Yumei Huang;Yueyue Yan;Mingdi Xia;Wei Zhou;Qian Zhang;Junhao Yan
通讯作者:L. Yang;T. Ni;Yumei Huang;Yueyue Yan;Mingdi Xia;Wei Zhou;Qian Zhang;Junhao Yan
DOI:10.3760/cma.j.cn112137-20221226-02698
发表时间:2023
期刊:中华医学杂志
影响因子:--
作者:赵绍彤;刘颖博;张倩;倪天翔;颜军昊
通讯作者:颜军昊
DOI:10.1080/14647273.2023.2262810
发表时间:2023-08
期刊:Human Fertility
影响因子:1.9
作者:Wenhao Yu;Chenxi Jin;Qian Zhang;T. Ni;Junhao Yan
通讯作者:Wenhao Yu;Chenxi Jin;Qian Zhang;T. Ni;Junhao Yan
DOI:10.1186/s40001-023-01492-x
发表时间:2023-11-21
期刊:EUROPEAN JOURNAL OF MEDICAL RESEARCH
影响因子:4.2
作者:Liu, Yang;Ni, Tianxiang;Zhao, Qing;Cui, Weiran;Lan, Xiangxin;Zhou, Tingting;Zhang, Qian;Yan, Junhao
通讯作者:Yan, Junhao
国内基金
海外基金
