Loss of CDYL Results in Suppression of CTNNB1 and Decreased Endometrial Receptivity
Loss of CDYL Results in Suppression of CTNNB1 and Decreased Endometrial Receptivity
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CDYL 缺失导致 CTNNB1 抑制和子宫内膜容受性降低
DOI：
10.3389/fcell.2020.00105
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发表时间：
2020-02-25
影响因子：
5.5
通讯作者：
Zhang, Aijun
中科院分区：
文献类型：
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作者：
Zhou, Xiaowei;Xu, Bufang;Zhang, Aijun
子宫内膜接受受损是复发植入失败（RIF）的主要原因之一，尽管尚未完全阐明了基本的分子机制。在本研究中，我们证明了类似（CDYL）在正常月经周期中分泌阶段的子宫内膜中高度表达。然而，在从患有RIF的女性获得的子宫内膜组织中，CDYL的表达与LIF的蛋白质水平保持一致，这是子宫内膜接受的标志。在CDYL敲击人子宫内膜Ishikawa细胞中，我们确定了1738个差异表达的基因（DEGS）。重要的是，在Ishikawa细胞以及主要的子宫内膜上皮细胞和基质细胞中，对CDYL抑制作用的反应大大降低，对CDYL的抑制作用大幅降低。此外，RIF患者的子宫内膜中CTNNB1WAS的表达也降低。这些结果表明，CTNNB1的表达受子宫内膜中的CDYL调节。细胞迁移受到Ishikawa细胞和原发性子宫基质细胞（ESC）（ESC）的CDYL敲低的损害，可以通过CDYL或CTNNB1过表达来挽救。总的来说，我们的发现表明，CDYL表达的降低可能会通过影响CTNNB1表达来抑制子宫内膜细胞迁移能力，这将导致RIF女性的子宫内膜接受能力不良。
Impaired endometrial receptivity is one of the major causes of recurrent implantation failure (RIF), although the underlying molecular mechanism has not been fully elucidated. In the present study, we demonstrated that chromodomain Y like (CDYL) was highly expressed in the endometrium at mid-secretory phase during the normal menstrual cycles. However, the expression of CDYL was downregulated in the endometrial tissues obtained from women with RIF, consistently with the protein level of LIF, which is a marker of endometrial receptivity. In CDYL-knockdown human endometrial Ishikawa cells, we identified 1738 differentially expressed genes (DEGs). Importantly, the catenin beta 1 (CTNNB1) expression was dramatically reduced responding to the CDYL inhibition, both in Ishikawa cells as well as the primary endometrial epithelial and stromal cells. In addition, the expression of CTNNB1was decreased in the endometrium from RIF patients as well. These results suggested that the expression of CTNNB1 was regulated by CDYL in endometrium. The cell migration was impaired by CDYL-knockdown in Ishikawa cells and primary endometrial stromal cells (ESCs), which could be rescued by CDYL or CTNNB1 overexpression. Collectively, our findings indicated that the decreased expression of CDYL may suppress endometrial cell migration capability by affecting CTNNB1 expression, which would contribute to poor endometrial receptivity in women with RIF.