Tan Yi, Li Meiling, Cox Sandra, Davis Marilyn K, Tawfik Ossama, Paria Bibhash C, Das Sanjoy K
Department of Pediatrics, Division of Reproductive and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232-2678, USA.
Dev Biol. 2004 Jan 1;265(1):181-95. doi: 10.1016/j.ydbio.2003.09.019.
Stromal cell polyploidy is a unique phenomenon that occurs during uterine decidualization following embryo implantation, although the developmental mechanism still remains elusive. The general consensus is that the aberrant expression and altered functional activity of cell cycle regulatory molecules at two particular checkpoints G1 to S and G2 to M in the cell cycle play an important role in the development of cellular polyploidy. Despite the compelling evidence of intrinsic cell cycle alteration, it has been implicated that the development of cellular polyploidy may be controlled by specific actions of extracellular growth regulators. Here we show a novel role for heparin-binding EGF-like growth factor (HB-EGF) in the developmental process of stromal cell polyploidy in mice. HB-EGF, which is one of the earliest known molecular mediators of implantation in mice and humans, promotes stromal cell polyploidy via upregulation of cyclin D3. Adenoviral delivery of antisense cyclin D3 attenuates cyclin D3 expression and abrogates HB-EGF-induced stromal cell polyploidy in vitro and in vivo. Collectively, the results demonstrate that the regulation of stromal cell polyploidy and decidualization induced by HB-EGF depend on cyclin D3 induction.
基质细胞多倍体是胚胎植入后子宫蜕膜化过程中出现的一种独特现象，但其发育机制仍不清楚。普遍的共识是，细胞周期中两个特定检查点（从G1到S以及从G2到M）处细胞周期调节分子的异常表达和功能活性改变在细胞多倍体的发育中起重要作用。尽管有确凿证据表明存在内在细胞周期改变，但有观点认为细胞多倍体的发育可能受细胞外生长调节因子的特定作用控制。在此，我们展示了肝素结合表皮生长因子（HB-EGF）在小鼠基质细胞多倍体发育过程中的新作用。HB-EGF是小鼠和人类已知最早的着床分子介质之一，它通过上调细胞周期蛋白D3促进基质细胞多倍体形成。反义细胞周期蛋白D3的腺病毒递送可减弱细胞周期蛋白D3的表达，并在体外和体内消除HB-EGF诱导的基质细胞多倍体形成。总体而言，结果表明HB-EGF诱导的基质细胞多倍体形成和蜕膜化依赖于细胞周期蛋白D3的诱导。
