Cyclin G1 and cyclin G2 are expressed in the periimplantation mouse uterus in a cell-specific and progesterone-dependent manner: evidence for aberrant regulation with Hoxa-10 deficiency.
Cyclin G1 and cyclin G2 are expressed in the periimplantation mouse uterus in a cell-specific and progesterone-dependent manner: evidence for aberrant regulation with Hoxa-10 deficiency.
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DOI：
10.1210/en.2004-1605
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发表时间：
2005-05
期刊：
影响因子：
4.8
通讯作者：
Li-min Yue;T. Daikoku;Xiao-Fan Hou;Meiling Li;Haibin Wang;H. Nojima;S. Dey;S. Das
中科院分区：
文献类型：
--
作者：
Li-min Yue;T. Daikoku;Xiao-Fan Hou;Meiling Li;Haibin Wang;H. Nojima;S. Dey;S. Das
由于子宫细胞特异性增殖、分化和凋亡在围着床期受到不同程度的调控，我们推测在这一时期子宫中也存在负细胞周期调控因子。这促使我们研究了两个负生长调控基因，细胞周期蛋白G1和细胞周期蛋白G2在小鼠子宫植入周中的作用。我们发现周期蛋白G1和周期蛋白G2基因在这一时期（妊娠第1-8天）在子宫中以时空方式受到差异调节。结果表明，细胞周期蛋白G1主要与着床前上皮细胞的分化和脱胞过程中基质细胞的增殖和分化有关，而细胞周期蛋白G2则与着床后囊胚部位腔内上皮细胞和基质细胞的终末分化和凋亡有关。药理学和遗传学研究证明，细胞周期蛋白G1的表达，而不是细胞周期蛋白G2，是由孕激素通过其核受体调节的。此外，这些基因的表达在子宫同源盒A-10突变体中异常上调，表明cyclin G1和cyclin G2基因是同源盒A-10的下游靶点，并对子宫细胞增殖产生负面影响。总之，我们目前和以前的研究表明，负细胞周期调节因子与促生长调节因子协同调节与着床和脱胞相关的子宫细胞特异性增殖、分化和凋亡。
Because uterine cell-specific proliferation, differentiation, and apoptosis are differentially regulated during the periimplantation period, we speculated that negative cell cycle regulators are also operative in the uterus during this period. This prompted us to examine the roles of two negative growth-regulatory genes, cyclin G1 and cyclin G2, in the periimplantation mouse uterus. We show that cyclin G1 and cyclin G2 genes are differentially regulated in the uterus during this period (d 1-8 of pregnancy) in a spatiotemporal manner. The results suggest that cyclin G1 is primarily associated with epithelial cell differentiation before implantation and stromal cell proliferation and differentiation during decidualization, whereas cyclin G2 is associated with terminal differentiation and apoptosis of the luminal epithelial and stromal cells at the site of blastocyst after implantation. Pharmacological and genetic studies provide evidence that the expression of cyclin G1, not cyclin G2, is regulated by progesterone via its nuclear receptor. Furthermore, the expression of these genes is aberrantly up-regulated in homeo box A-10 mutant uteri, suggesting that cyclin G1 and cyclin G2 genes act as downstream targets of homeobox A-10 and negatively impact uterine cell proliferation. Collectively, our present and previous studies suggest that negative cell cycle regulators collaborate with growth-promoting regulators in regulating uterine cell-specific proliferation, differentiation, and apoptosis relevant to implantation and decidualization.