Control of regional decidualization in implantation: Role of FoxM1 downstream of Hoxa10 and cyclin D3.
Control of regional decidualization in implantation: Role of FoxM1 downstream of Hoxa10 and cyclin D3.
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DOI：
10.1038/srep13863
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发表时间：
2015-09-09
影响因子：
4.6
通讯作者：
Das SK
中科院分区：
文献类型：
--
作者：
Gao F;Bian F;Ma X;Kalinichenko VV;Das SK
在子宫系膜三角和次级蜕膜区（SDZ）位置，适当调节区域子宫基质细胞蜕膜化对成功妊娠至关重要，尽管其调节机制仍知之甚少。在这方面，现有的动物模型，特别是允许位点特异性蜕膜化的机制分析是非常有限的。我们的研究发现，FoxM1，叉头盒转录因子的表达增强，在蜕膜化过程中受到调节，其在小鼠中的条件性缺失揭示了植入失败与区域蜕膜化缺陷，如一个更小的子宫系膜蜕膜与扩大SDZ。在体内和体外的蜕膜化过程中的细胞周期进展的分析表明，FoxM1的损失elaborate二倍体细胞缺陷与增强逮捕前有丝分裂和伴随的多倍体上调。我们进一步表明，Hoxa10和细胞周期蛋白D3，两个蜕膜标记，控制转录调控和FoxM1的核内蛋白易位在多倍体细胞，分别。总体而言，我们认为，适当的区域蜕膜化和多倍体的发展需要FoxM1信号下游的Hoxa10和细胞周期蛋白D3。
Appropriate regulation of regional uterine stromal cell decidualization in implantation, at the mesometrial triangle and secondary decidual zone (SDZ) locations, is critical for successful pregnancy, although the regulatory mechanisms remain poorly understood. In this regard, the available animal models that would specifically allow mechanistic analysis of site-specific decidualization are strikingly limited. Our study found that heightened expression of FoxM1, a Forkhead box transcription factor, is regulated during decidualization, and its conditional deletion in mice reveals failure of implantation with regional decidualization defects such as a much smaller mesometrial decidua with enlarged SDZ. Analysis of cell cycle progression during decidualization both in vivo and in vitro demonstrates that the loss of FoxM1 elicits diploid cell deficiency with enhanced arrests prior to mitosis and concomitant upregulation of polyploidy. We further showed that Hoxa10 and cyclin D3, two decidual markers, control transcriptional regulation and intra-nuclear protein translocation of FoxM1 in polyploid cells, respectively. Overall, we suggest that proper regional decidualization and polyploidy development requires FoxM1 signaling downstream of Hoxa10 and cyclin D3.