Kong Shuangbo, Han Xue, Cui Tongtong, Zhou Chan, Jiang Yufei, Zhang Hangxiao, Wang Bingyan, Wang Haibin, Zhang Shuang
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
Endocrine. 2016 Aug;53(2):595-606. doi: 10.1007/s12020-016-0894-9. Epub 2016 Feb 24.
Uterine decidualization characterized by stromal cell proliferation and differentiation is critical to the establishment of pregnancy in many species. Progesterone is a key factor in regulating endometrial cell decidualization, however, the molecular basis involved in mediating the effects of progesterone during decidualization remains largely unknown. We report here that the DNA replication licensing factor MCM2, one of the conserved set of six-related proteins (MCM complex: MCM2-7) essential for eukaryotic DNA replication, is dynamically expressed in both proliferative and differentiated stromal cells during mouse periimplantation uterus. Applying PR-knockout mouse model and pharmacological strategy, we further found that the expression of Mcm2 is induced by progesterone action in the mouse uterine stroma. Employing a primary cell culture system, we further demonstrated that siRNA-mediated silencing of MCM2 arrests the cell cycle at G1-S transition during stromal cell proliferation. Moreover, the downregulation of Mcm2 could also compromise stromal cell differentiation. Collectively, our studies uncovered the role of a unique DNA replication licensing molecule MCM2 in mediating Progesterone-induced stromal cell decidualization in mouse uterus.
以基质细胞增殖和分化为特征的子宫蜕膜化对许多物种妊娠的建立至关重要。孕酮是调节子宫内膜细胞蜕膜化的关键因素，然而，在蜕膜化过程中介导孕酮作用的分子基础仍 largely unknown。我们在此报告，DNA复制许可因子MCM2，是真核生物DNA复制所必需的一组六个相关蛋白（MCM复合体：MCM2 - 7）中的一个保守成员，在小鼠植入前子宫的增殖和分化基质细胞中均有动态表达。应用PR基因敲除小鼠模型和药理学策略，我们进一步发现Mcm2的表达在小鼠子宫基质中由孕酮作用诱导。利用原代细胞培养系统，我们进一步证明，siRNA介导的MCM2沉默在基质细胞增殖过程中将细胞周期阻滞在G1 - S期转换。此外，Mcm2的下调也会损害基质细胞分化。总体而言，我们的研究揭示了独特的DNA复制许可分子MCM2在介导孕酮诱导的小鼠子宫基质细胞蜕膜化中的作用。
