Immune-responsive gene 1 is a novel target of progesterone receptor and plays a critical role during implantation in the mouse
Immune-responsive gene 1 is a novel target of progesterone receptor and plays a critical role during implantation in the mouse
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DOI：
10.1210/en.2003-0585
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发表时间：
2003-12-01
期刊：
影响因子：
4.8
通讯作者：
Bagchi, IC
中科院分区：
文献类型：
--
作者：
Cheon, YP;Xu, XP;Bagchi, IC
类固醇激素黄体酮 (P) 是囊胚植入过程中子宫容受性的关键调节剂。该激素通过核 P 受体 (PR) 发挥作用，调节各种子宫细胞类型中特定基因网络的表达。为了确定子宫容受性的 P 调节途径，我们之前使用寡核苷酸微阵列来分析植入时对 PR 拮抗剂 RU486 的子宫 mRNA 谱。我们报道了与免疫反应基因 1 (Irg1) 相对应的 mRNA，这是一种先前描述的脂多糖诱导基因，是在植入前子宫中被 RU486 显着下调的几种 mRNA 之一。在本研究中，我们进行了原位杂交，结果表明 P 刺激去势野生型小鼠子宫腔上皮细胞中 Irg1 mRNA 的合成，但不刺激 PR 敲除小鼠的子宫腔上皮细胞。我们还报道，在第 3 天和第 5 天之间，Irg1 mRNA 在妊娠子宫的管腔上皮中被诱导，与植入窗口重叠。为了研究 Irg1 在植入过程中的功能，我们将正义或反义寡脱氧核苷酸注射到植入前的小鼠子宫中。用反义寡脱氧核苷酸治疗可抑制 Irg1 mRNA 表达，而不影响妊娠子宫中不相关的 mRNA。这种干预还伴随着胚胎植入受损，表明该表型与 Irg1 mRNA 的抑制有关。总的来说，我们的研究将 Irg1 确定为妊娠子宫 PR 的新靶点，并揭示它是导致着床的早期事件的关键调节因子。
The steroid hormone progesterone (P) is a critical regulator of uterine receptivity during blastocyst implantation. The hormone acts through nuclear P receptors (PRs) to modulate the expression of specific gene networks in various uterine cell types. To identify the P-regulated pathways underlying uterine receptivity, we previously used oligonucleotide microarrays to analyze uterine mRNA profiles at the time of implantation in response to RU486, a PR antagonist. We reported that the mRNA corresponding to the immune-responsive gene 1 (Irg1), a previously described lipopolysaccharide-inducible gene, is one of the several mRNAs that are markedly down-regulated by RU486 in the preimplantation uterus. In the present study, we performed in situ hybridization to show that P stimulates Irg1 mRNA synthesis in the luminal epithelial cells of uteri of ovariectomized wild-type but not PR knockout mice. We also report that Irg1 mRNA was induced in the luminal epithelium of pregnant uterus between d 3 and 5, overlapping the window of implantation. To investigate the function of Irg1 during implantation, we administered sense or antisense oligodeoxynucleotides into preimplantation mouse uteri. Treatment with antisense oligodeoxynucleotides led to suppression in Irg1 mRNA expression without affecting unrelated mRNAs in the pregnant uterus. This intervention was also accompanied by impairment in embryo implantation, indicating that the phenotype is linked to the suppression of Irg1 mRNA. Collectively, our studies identified Irg1 as a novel target of PR in the pregnant uterus and also revealed that it is a critical regulator of the early events leading to implantation.