Uterine Foxl2 regulates the adherence of the Trophectoderm cells to the endometrial epithelium.
Uterine Foxl2 regulates the adherence of the Trophectoderm cells to the endometrial epithelium.
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DOI：
10.1186/s12958-018-0329-y
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发表时间：
2018-02-07
期刊：
影响因子：
--
通讯作者：
Gershon E
中科院分区：
文献类型：
--
作者：
Elbaz M;Hadas R;Bilezikjian LM;Gershon E
叉头转录因子L2 （FOXL2）是叉头家族的一员，在生殖中起着重要的作用。最近的研究表明，FOXL2在人类和牛子宫内膜中表达，其水平在怀孕期间波动。在本研究中，我们旨在评估FOXL2在胚胎着床中的表达和功能。分离不同妊娠天数的小鼠子宫，分析FOXL2的表达和定位。我们进一步采用慢病毒策略，分别在非接受性人子宫内膜AN3-CA细胞和接受性Ishikawa细胞中敲低或过表达FOXL2。将这些基因修饰的细胞与感染了对照慢病毒的细胞进行比较，以确定FOXL2在滋养外胚层细胞中的功能。子宫内膜粘附与已知参与子宫接受性获得的基因表达相关。我们报道FOXL2在小鼠子宫腔上皮和子宫肌层中均有表达，并且在着床前其表达下降。我们发现，表达低FOXL2水平的子宫内膜细胞，无论是内源性的还是基因操纵的，都与小鼠囊胚或人Jeg3球体和小鼠囊胚的较高附着率相关。因此，低foxl2水平与Wnt/Fzd和凋亡通路组分的表达水平变化有关，这两个通路都与子宫接受性有关。此外，FOXL2的表达与g蛋白信号蛋白2 （Rgs2）和细胞因子表达呈负相关。这些结果表明FOXL2干扰胚胎附着。更好地了解子宫中FOXL2的功能可能会为治疗反复着床失败导致的不孕症提供新的策略。本文的在线版本（10.1186/s12958-018-0329-y）包含补充材料，仅供授权用户使用。
Forkhead Transcription Factor L2 (FOXL2) is a member of the forkhead family with important roles in reproduction. Recent studies showed that FOXL2 is expressed in human and bovine endometrium and that its levels fluctuate during pregnancy. In this study, we aimed at evaluating the expression and function of FOXL2 in embryo implantation. Mouse uteri at different days of pregnancy were isolated and analyzed for the expression and localization of FOXL2. A lentiviral strategy was further employed to either knockdown or overexpress FOXL2 in non-receptive human endometrial AN3-CA cells and in receptive Ishikawa cells, respectively. These genetically modified cells were compared to cells infected with a control lentivirus to determine the function of FOXL2 in trophectoderm cells adherence to Endometrial Epithelium was associated with the expression of genes known to be involved in acquisition of uterine receptivity. We report that FOXL2 is expressed in both, the luminal epithelium and the myometrium of the mouse uterus and that its expression declines prior to implantation. We found that endometrial cells expressing low FOXL2 levels, either endogenous or genetically manipulated, were associated with a higher attachment rate of mouse blastocysts or human Jeg3 spheroids and mouse blastocysts. In accordance, low-FOXL2 levels were associated with changes in the expression level of components of the Wnt/Fzd and apoptotic pathways, both of which are involved in uterine receptivity. Furthermore, FOXL2 expression was inversely correlated with G-protein signaling protein 2 (Rgs2) and cytokine expression. These results suggest that FOXL2 interferes with embryo attachment. Better understanding of the function of FOXL2 in the uterus would possibly suggest novel strategies for treatment of infertility attributed to repeated implantation failure. The online version of this article (10.1186/s12958-018-0329-y) contains supplementary material, which is available to authorized users.
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