Kashiwagi Aki, DiGirolamo Carla M, Kanda Yoshiaki, Niikura Yuichi, Esmon Charles T, Hansen Thomas R, Shioda Toshi, Pru James K
Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital, Harvard Medical School, Thier Research Building, Room 931, 55 Fruit Street, Boston, Massachusetts 02114, USA.
Endocrinology. 2007 Sep;148(9):4173-84. doi: 10.1210/en.2007-0268. Epub 2007 May 17.
Transcriptomal changes in the uterine endometrium induced in response to the implanting embryo remain largely unknown. In this study, using Affymetrix mRNA expression microarray analysis, we identified genes differentially expressed in the murine endometrium in the presence or absence of the embryo. Compared with the pseudopregnant deciduoma induced by a mechanical stimulus in the absence of an embryo, approximately 1500 genes (753 up-regulated, 686 down-regulated; P < 0.05) were differentially expressed by at least 1.2-fold in the uterine decidua of pregnancy. Most of these genes fall into five major biological categories that include binding (45%), catalysis (24%), signal transduction (10%), transcriptional regulators (5%), and transporters (5%). This strong, embryo-induced transcriptomal impact represented approximately 10% of the total number of genes expressed in the decidualizing endometrium. Validation studies with mRNA and protein confirmed existence of the phylogenetically conserved, embryo-regulated genes involved in the following: 1) hemostasis and inflammation; 2) interferon signaling; 3) tissue growth and remodeling; and 4) natural killer cell function. Interestingly, whereas expression of many growth factors and their cognate receptors were not different between the decidual and deciduomal endometria, a number of proteases that degrade growth factors were selectively up-regulated in the decidual tissue. Increased expression of IGF and activin A neutralizing factors (i.e. HtrA1 and Fstl3) correlated with reduced stromal cell mitosis, tissue growth, and mitogenic signaling in the decidual endometrium. These results support the hypothesis that the implanting murine embryo takes a proactive role in modulating endometrial gene expression and development during early gestation.
针对植入胚胎所诱导的子宫子宫内膜转录组变化，目前仍知之甚少。在本研究中，我们使用Affymetrix mRNA表达微阵列分析，鉴定了在有或没有胚胎存在的情况下，小鼠子宫内膜中差异表达的基因。与在无胚胎情况下由机械刺激诱导的假孕蜕膜瘤相比，在妊娠子宫蜕膜中，约1500个基因（753个上调，686个下调；P < 0.05）的表达差异至少为1.2倍。这些基因大多可分为五个主要生物学类别，包括结合（45%）、催化（24%）、信号转导（10%）、转录调节因子（5%）和转运蛋白（5%）。这种由胚胎强烈诱导的转录组影响约占蜕膜化子宫内膜中表达基因总数的10%。对mRNA和蛋白质的验证研究证实了以下进化上保守的、受胚胎调节的基因的存在：1）止血和炎症；2）干扰素信号传导；3）组织生长和重塑；4）自然杀伤细胞功能。有趣的是，虽然许多生长因子及其同源受体在蜕膜和蜕膜瘤子宫内膜之间的表达没有差异，但一些降解生长因子的蛋白酶在蜕膜组织中被选择性上调。IGF和激活素A中和因子（即HtrA1和Fstl3）表达的增加与蜕膜子宫内膜中基质细胞有丝分裂、组织生长和有丝分裂信号的减少相关。这些结果支持了这样一种假说，即植入的小鼠胚胎在妊娠早期对调节子宫内膜基因表达和发育起着积极作用。
