目的探讨调节性T细胞(Treg)和Notch1信号通路在原因不明复发性自然流产(URSA)中的作用。方法流式细胞仪检测URSA患者(URSA组)及正常妊娠妇女(对照组)蜕膜CD4^+CD25^+T细胞Treg表达比例,real time RT-PCR及Western blotting检测蜕膜中CD4...目的探讨调节性T细胞(Treg)和Notch1信号通路在原因不明复发性自然流产(URSA)中的作用。方法流式细胞仪检测URSA患者(URSA组)及正常妊娠妇女(对照组)蜕膜CD4^+CD25^+T细胞Treg表达比例,real time RT-PCR及Western blotting检测蜕膜中CD4^+T细胞中Notch1信号通路和叉头转录因子家族3(Foxp3)表达情况。结果 URSA组CD4^+CD25^+T细胞/淋巴细胞、CD4^+Foxp3^+T细胞/淋巴细胞和CD4^+Foxp3^+T细胞/CD4^+T细胞比例均低于对照组(P<0.05)。URSA组CD4^+T细胞中Notch1-Ic、RBPJκ、Foxp3 m RNA及蛋白表达均低于对照组。结论 URSA患者蜕膜CD4^+T细胞中Notch1信号通路和Foxp3表达下调,CD4^+CD25^+T细胞表达比例下降,提示URSA患者Notch1信号通路和Foxp3表达下调可能阻碍CD4^+T细胞转化为CD4^+CD25^+T细胞,进而诱发免疫排斥,诱导流产。展开更多
The causes of recurrent spontaneous abortion (RSA) and fetal malformations are multifactorial and unclear in most cases. Environmental, maternal, and genetic factors have been shown to contribute to these defects. Who...The causes of recurrent spontaneous abortion (RSA) and fetal malformations are multifactorial and unclear in most cases. Environmental, maternal, and genetic factors have been shown to contribute to these defects. Whole-exome sequencing (WES) is widely used to detect genetic variations associated with human diseases and has recently been successfully applied to unveil genetic causes of unexplained recurrent spontaneous abortion (URSA) and fetal malformations. Here, we review the current discovery and diagnosis strategies to identify the underlying pathogenic mutations of URSA and fetal malformations using WES technology and propose to further develop WES, both to advance our understanding of these diseases and to eventually lead to targeted therapies for reproductive disorders.展开更多
文摘目的探讨调节性T细胞(Treg)和Notch1信号通路在原因不明复发性自然流产(URSA)中的作用。方法流式细胞仪检测URSA患者(URSA组)及正常妊娠妇女(对照组)蜕膜CD4^+CD25^+T细胞Treg表达比例,real time RT-PCR及Western blotting检测蜕膜中CD4^+T细胞中Notch1信号通路和叉头转录因子家族3(Foxp3)表达情况。结果 URSA组CD4^+CD25^+T细胞/淋巴细胞、CD4^+Foxp3^+T细胞/淋巴细胞和CD4^+Foxp3^+T细胞/CD4^+T细胞比例均低于对照组(P<0.05)。URSA组CD4^+T细胞中Notch1-Ic、RBPJκ、Foxp3 m RNA及蛋白表达均低于对照组。结论 URSA患者蜕膜CD4^+T细胞中Notch1信号通路和Foxp3表达下调,CD4^+CD25^+T细胞表达比例下降,提示URSA患者Notch1信号通路和Foxp3表达下调可能阻碍CD4^+T细胞转化为CD4^+CD25^+T细胞,进而诱发免疫排斥,诱导流产。
基金supported by the National Natural Science Foundation of China (Nos. 31522034 and 81730038)the National High Technology Research and Development Program Grant (2015AA020407)
文摘The causes of recurrent spontaneous abortion (RSA) and fetal malformations are multifactorial and unclear in most cases. Environmental, maternal, and genetic factors have been shown to contribute to these defects. Whole-exome sequencing (WES) is widely used to detect genetic variations associated with human diseases and has recently been successfully applied to unveil genetic causes of unexplained recurrent spontaneous abortion (URSA) and fetal malformations. Here, we review the current discovery and diagnosis strategies to identify the underlying pathogenic mutations of URSA and fetal malformations using WES technology and propose to further develop WES, both to advance our understanding of these diseases and to eventually lead to targeted therapies for reproductive disorders.
