CD44/c-Src调控PECAM1低表达影响反复着床失败患者子宫内膜容受性的分子机制

批准号:
81873857
项目类别:
面上项目
资助金额:
57.0 万元
负责人:
张爱军
依托单位:
学科分类:
H0420.辅助生殖
结题年份:
2022
批准年份:
2018
项目状态:
已结题
项目参与者:
周晓薇、姜璐、张元亮、张丹、邱青松、王铭杰、郭枫、周明娟
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中文摘要
子宫内膜容受性低下所致反复着床失败(RIF)是目前辅助生殖技术临床难题。我们研究发现:PECAM1低表达影响RIF患者子宫内膜容受性;CD44与PECAM1在月经周期动态表达模式一致;CD44及其经典下游因子c-Src在RIF子宫内膜中表达亦降低;干扰人子宫内膜癌细胞CD44表达,c-Src和PECAM1表达下降。那么,CD44/c-Src是否通过调控PECAM1低表达而影响RIF患者子宫内膜容受性?尚待深入研究。本项目将进一步从细胞水平揭示CD44对子宫内膜容受性的影响,并以条件性敲除CD44小鼠验证;通过探讨CD44/c-Src调控PECAM1表达的信号传导通路,阐明其影响内膜容受性的分子机制;通过补救实验,验证该通路中关键分子在改善内膜容受性中的作用;通过检测宫腔液中游离靶分子,探寻内膜容受性标志物。本项研究对于阐明RIF发病机制、发现改善内膜容受性药物靶点具重要理论意义和临床价值。
英文摘要
Recurrent implantation failure (RIF), mostly caused by low endometrial receptivity, is a clinical challenge needed to be eagerly resolved. Our previous study has found that the low expression of PECAM1 affected the endometrial receptivity of RIF patients. And the expression pattern of CD44 in endometrium was consistent with that of PECAM1 in different stages of menstruation. Moreover, the expression levels of CD44 and its classical downstream factor c-Src were decreased in RIF patients as well. After interfering the expression of CD44 in endometrial carcinoma cells, the expression of c-Src and PECAM1 decreased significantly. Whether CD44/c-Src regulates endometrial receptivity via PECAM1-dependent mechanism remains unknown. This study will further reveal the effect of CD44 on endometrial receptivity from the cellular level, which will be verified by conditional uterine CD44 knockout female mice. We will investigate the effect of CD44/c-Src pathway in regulating the expression of PECAM1 and clarifying its molecular mechanism on modulating endometrial receptivity. By performing rescue experiment we will testify the effect of critical molecules in this signal pathway on improving endometrial receptivity. By detecting the newly target molecules in uterine fluid we will discover the markers of endometrial receptivity. This study would be of great theoretical significance and clinical value for elucidating the pathogenesis of RIF and finding novel drug targets for improving endometrial receptivity.
子宫内膜容受性低下所致反复着床失败(RIF)是目前辅助生殖技术临床难题。本项目研究阐明RIF患者分泌中期低表达的CD44v3通过下调人子宫内膜间质细胞的增殖和蜕膜化功能,从而抑制子宫内膜容受性,部分揭示了RIF患者子宫内膜容受性低下的病理机制。本项目同样关注其他可改善子宫内膜容受性的新药物靶点及预测子宫内膜容受性的新标志物,并发现RIF患者分泌中期子宫内膜低表达的PIBF1可能通过下调IL6/p-STAT3信号通路,抑制HESCs的增殖及蜕膜化,影响RIF患者子宫内膜容受性。本项研究对于阐明RIF发病机制、发现改善内膜容受性药物靶点具重要理论意义和临床价值。
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
Decreased CD44v3 Expression Impairs Endometrial Stromal Cell Decidualization in Women With Recurrent Implantation Failure
CD44v3 表达减少会损害反复着床失败女性的子宫内膜基质细胞蜕膜化
DOI:10.21203/rs.3.rs-1043935/v1
发表时间:2021-11
期刊:Reproductive Biology and Endocrinology
影响因子:4.4
作者:Xiaowei Zhou;Yi Cao;mingjuan Zhou;Mi Han;mengyu Liu;Yanqin Hu;Bufang Xu;Aijun Zhang
通讯作者:Aijun Zhang
Cell-Free Fat Extract Improves Ovarian Function and Fertility in Mice With Advanced Age.
无细胞脂肪提取物可改善高龄小鼠的卵巢功能和生育能力
DOI:10.3389/fendo.2022.912648
发表时间:2022
期刊:FRONTIERS IN ENDOCRINOLOGY
影响因子:5.2
作者:Liu, Mengyu;Li, Wenzhu;Zhou, Xiaowei;Zhou, Mingjuan;Zhang, Wenjie;Liu, Qiang;Zhang, Aijun;Xu, Bufang
通讯作者:Xu, Bufang
GnRH antagonist alters the migration of endometrial epithelial cells by reducing CKB
GnRH 拮抗剂通过减少 CKB 改变子宫内膜上皮细胞的迁移
DOI:10.1530/rep-19-0578
发表时间:2020-06-01
期刊:REPRODUCTION
影响因子:3.8
作者:Chen, Qian;Fan, Yong;Xu, Chen
通讯作者:Xu, Chen
GnRH Antagonist Protocol With Cessation of Cetrorelix on Trigger Day Improves Embryological Outcomes for Patients With Sufficient Ovarian Reserve.
GnRH 拮抗剂方案在触发日停止西曲瑞克可改善卵巢储备充足患者的胚胎学结果
DOI:10.3389/fendo.2021.758896
发表时间:2021
期刊:Frontiers in endocrinology
影响因子:5.2
作者:Xu H;Zhao S;Gao X;Wu X;Xia L;Zhang D;Li J;Zhang A;Xu B
通讯作者:Xu B
Decreased PIBF1/IL6/p-STAT3 during the mid-secretory phase inhibits human endometrial stromal cell proliferation and decidualization.
分泌中期PIBF1/IL6/p-STAT3减少抑制人子宫内膜基质细胞增殖和蜕膜化
DOI:10.1016/j.jare.2020.09.002
发表时间:2021-05
期刊:Journal of advanced research
影响因子:10.7
作者:Zhou M;Xu H;Zhang D;Si C;Zhou X;Zhao H;Liu Q;Xu B;Zhang A
通讯作者:Zhang A
AIF-1高表达激活p38MAPK信号致反复着床失败患者子宫内膜容受性下降的分子机制
- 批准号:--
- 项目类别:面上项目
- 资助金额:52万元
- 批准年份:2022
- 负责人:张爱军
- 依托单位:
CDYL/Kisspeptin/KISS1R信号通路异常致卵巢储备功能下降的机制研究
- 批准号:82071596
- 项目类别:面上项目
- 资助金额:55万元
- 批准年份:2020
- 负责人:张爱军
- 依托单位:
ASH1L和JMJD3在人卵子成熟和种植前胚胎发育中的作用及调控机制
- 批准号:81370763
- 项目类别:面上项目
- 资助金额:70.0万元
- 批准年份:2013
- 负责人:张爱军
- 依托单位:
国内基金
海外基金
