Abstract：
BACKGROUND: This study aims to identify metabolomic signatures in uterine fluid of women with idiopathic recurrent spontaneous miscarriage (IRSM) during window of implantation (WOI). Also, glucose transporters GLUT3 and GLUT4 and proteins of PI3K-Akt signaling pathway in endometrial tissue are assessed.
METHODS: Paired uterine fluid and endometrial biopsies were collected during WOI from women with IRSM (n = 24) and healthy women with azoospermic male partners as controls (n = 15). NMR metabolomics was used to identify the dysregulated metabolites in uterine fluid of IRSM women. Additionally, proteins and glucose transporters were investigated in the endometrial tissue using immunohistochemistry (IHC) and western blotting.
RESULTS: Uterine fluid metabolomics indicated eleven metabolites to be significantly downregulated in IRSM. While expression levels of PI3K (p85), PI3K (p110), p-Akt (Thr308), p-Akt (Ser473), GLUT3 and GLUT4 were significantly downregulated in endometrial tissue of these women, p-IKK α/β (Ser176/180) and p-NFkBp65 (Ser536) were significantly increased.
CONCLUSIONS: Our findings suggest that dysregulation of PI3K/Akt pathway in the uterine microenvironment could be a likely cause of endometrial dysfunction, thereby affecting implantation. Further studies on the downstream effects of the Akt signaling pathway in-vitro for improved understanding of the Akt-mediated cellular responses in IRSM is, therefore, warranted.
METHODS: Paired uterine fluid and endometrial biopsies were collected during WOI from women with IRSM (n = 24) and healthy women with azoospermic male partners as controls (n = 15). NMR metabolomics was used to identify the dysregulated metabolites in uterine fluid of IRSM women. Additionally, proteins and glucose transporters were investigated in the endometrial tissue using immunohistochemistry (IHC) and western blotting.
RESULTS: Uterine fluid metabolomics indicated eleven metabolites to be significantly downregulated in IRSM. While expression levels of PI3K (p85), PI3K (p110), p-Akt (Thr308), p-Akt (Ser473), GLUT3 and GLUT4 were significantly downregulated in endometrial tissue of these women, p-IKK α/β (Ser176/180) and p-NFkBp65 (Ser536) were significantly increased.
CONCLUSIONS: Our findings suggest that dysregulation of PI3K/Akt pathway in the uterine microenvironment could be a likely cause of endometrial dysfunction, thereby affecting implantation. Further studies on the downstream effects of the Akt signaling pathway in-vitro for improved understanding of the Akt-mediated cellular responses in IRSM is, therefore, warranted.
摘要：
背景：本研究旨在确定植入窗口（WOI）期间特发性复发性自发性流产（IRSM）女性子宫液中的代谢组学特征。此外，评估了子宫内膜组织中葡萄糖转运蛋白GLUT3和GLUT4以及PI3K-Akt信号通路的蛋白质。
方法：在WOI期间从患有IRSM的女性（n=24）和以无精子症男性伴侣为对照的健康女性（n=15）收集配对的子宫液和子宫内膜活检。NMR代谢组学用于鉴定IRSM妇女子宫液中失调的代谢产物。此外,使用免疫组织化学(IHC)和蛋白质印迹法检测子宫内膜组织中的蛋白质和葡萄糖转运蛋白.
结果：子宫液代谢组学显示11种代谢产物在IRSM中显著下调。虽然PI3K（p85）的表达水平，PI3K(p110),p-Akt(Thr308),p-Akt(Ser473),GLUT3和GLUT4在这些妇女的子宫内膜组织中显著下调，p-IKKα/β(Ser176/180)和p-NFkBp65(Ser536)显著升高。
结论：我们的研究结果表明，子宫微环境中PI3K/Akt通路的失调可能是子宫内膜功能障碍的一个可能原因。从而影响植入。进一步研究Akt信号通路在体外的下游作用，以提高对Akt介导的细胞反应在IRSM中的理解，因此,保证。
方法：在WOI期间从患有IRSM的女性（n=24）和以无精子症男性伴侣为对照的健康女性（n=15）收集配对的子宫液和子宫内膜活检。NMR代谢组学用于鉴定IRSM妇女子宫液中失调的代谢产物。此外,使用免疫组织化学(IHC)和蛋白质印迹法检测子宫内膜组织中的蛋白质和葡萄糖转运蛋白.
结果：子宫液代谢组学显示11种代谢产物在IRSM中显著下调。虽然PI3K（p85）的表达水平，PI3K(p110),p-Akt(Thr308),p-Akt(Ser473),GLUT3和GLUT4在这些妇女的子宫内膜组织中显著下调，p-IKKα/β(Ser176/180)和p-NFkBp65(Ser536)显著升高。
结论：我们的研究结果表明，子宫微环境中PI3K/Akt通路的失调可能是子宫内膜功能障碍的一个可能原因。从而影响植入。进一步研究Akt信号通路在体外的下游作用，以提高对Akt介导的细胞反应在IRSM中的理解，因此,保证。
