Paired‐like homeodomain transcription factor 2 affects endometrial cell function and embryo implantation through the Wnt/β‐catenin pathway
Paired‐like homeodomain transcription factor 2 affects endometrial cell function and embryo implantation through the Wnt/β‐catenin pathway
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DOI：
10.1002/cbin.11636
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发表时间：
2021-05
影响因子：
3.9
通讯作者：
Hongshuo Zhang;J. Qi;Jinqiu Guo;Yufei Wang;Y. Guan;Jianhui Fan;Linlin Sui;Yuefei Xu;Li Kong;B. Yan;Y. Kong
中科院分区：
文献类型：
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作者：
Hongshuo Zhang;J. Qi;Jinqiu Guo;Yufei Wang;Y. Guan;Jianhui Fan;Linlin Sui;Yuefei Xu;Li Kong;B. Yan;Y. Kong
胚胎的成功植入对哺乳动物的怀孕至关重要。这个复杂的过程不可避免地依赖于子宫内膜的发育。配对样同源结构域转录因子2 （PITX2）参与多种生物学过程，但其是否参与胚胎着床尚未见报道。在本研究中，我们旨在研究胚胎着床过程中子宫中PITX2的表达和调控。我们发现PITX2在人子宫内膜分泌期升高。妊娠小鼠模型的结果显示，PITX2在整个着床期小鼠子宫内膜组织中的表达具有时空性，并且在着床时显著上调。有趣的是，PITX2主要在妊娠第2.5 ~ 3.5期的腺上皮细胞中表达，而第5.5 ~ 6.5期的间质细胞中表达较多。在体外，PITX2通过Wnt/β‐catenin信号通路调节子宫内膜细胞增殖、迁移、侵袭等功能。此外，子宫角注射PITX2小干扰RNA后，胚胎着床率明显降低。这些结果证实了PITX2对子宫内膜细胞生理功能和胚胎着床的影响，提示其可能参与着床过程中子宫内膜的调控机制。
The successful implantation of embryos is crucial for pregnancy in mammals. This complex process is inevitably dependent on the development of the endometrium. The paired‐like homeodomain transcription factor 2 (PITX2) is involved in a variety of biological processes, but whether it is involved in embryo implantation has not been reported. In this study, we aimed to investigate uterine expression and regulation of PITX2 during implantation. We found that PITX2 was elevated in the human endometrium in the secretory phase. The results of the pregnant mouse models showed that PITX2 expression was spatiotemporal in mouse endometrial tissue throughout peri‐implantation period, and it was significantly upregulated at the time of implantation. Interestingly, PITX2 was mainly localized to the glandular epithelium cells on D2.5‐3.5 of pregnancy, while D5.5‐6.5 was largely expressed in stromal cells. In vitro, PITX2 regulated endometrial cells proliferation, migration, invasion, and other functions through the Wnt/β‐catenin signaling pathway. In addition, a significant decrease in the rate of embryo implantation was observed after injecting PITX2 small interfering RNA into the uterine horn. These results demonstrate the effects of PITX2 on the physiological function of endometrial cells and embryo implantation, suggesting a role in the endometrial regulatory mechanism during implantation.