Developmental expression of the cyclo-oxygenase-1 and cyclo-oxygenase-2 genes in the peri-implantation mouse uterus and their differential regulation by the blastocyst and ovarian steroids
Developmental expression of the cyclo-oxygenase-1 and cyclo-oxygenase-2 genes in the peri-implantation mouse uterus and their differential regulation by the blastocyst and ovarian steroids
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DOI：
10.1677/jme.0.0160107
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发表时间：
1996-04-01
影响因子：
3.5
通讯作者：
Dey, SK
中科院分区：
文献类型：
--
作者：
Chakraborty, I;Das, SK;Dey, SK
环氧合酶（考克斯）是一种将花生四烯酸转化为前列腺素（PGs）的限速酶，以两种异构体考克斯-1和考克斯-2存在。在啮齿类动物中，胚泡贴壁部位的子宫血管通透性增加是着床过程中最早的先决条件之一。这一事件之前是普遍的子宫水肿和管腔关闭，并符合滋养外胚层和管腔上皮之间的初始附着反应。血管活性前列腺素参与这些过程。在这里，我们证明，考克斯基因差异调节围着床期小鼠子宫。在着床前（1-4天），考克斯-1基因主要在第4天在子宫上皮中表达，直到晚上附着反应开始，之后表达下调。这种考克斯-1表达与子宫腔闭合所需的子宫水肿一致。相反，考克斯-2基因表达的腔上皮和上皮下基质细胞在反子宫系膜极专门围绕胚泡在第4天的附着反应的时间，并持续通过第5天的早晨。在孕酮（P-4）处理的延迟着床过程中，该子宫基因在囊胚附着部位不表达，但在雌二醇-17 β（E（2））终止延迟后，在激活的囊胚周围的子宫中很容易诱导。结果提示，考克斯-2催化的PG合成在子宫局部血管通透性增加和贴附反应中起重要作用。考克斯-1基因，下调的时间从第4天的附着反应再次表达在系膜和反系膜次级蜕膜床的第7和第8天。这些结果表明，PGs产生的考克斯-1参与蜕膜化和/或持续局部子宫内膜血管通透性观察在此期间。相比之下，第4天和第5天在反子宫系膜极表达的考克斯-2基因从第6天起将其表达转移到子宫系膜极。这些结果表明，PGs在这个网站上产生的考克斯-2参与血管生成的建立胎盘。在卵巢切除的小鼠中，通过P-4和E的联合处理，上皮中的考克斯-1基因被诱导（2）。然而，P-4和/或E（2）处理未能影响子宫考克斯-2基因。总之，这些结果表明，子宫考克斯-1基因的影响，卵巢类固醇，而考克斯-2基因的调控植入胚泡在早期妊娠。
Cyclo-oxygenase (COX) is a rate-limiting enzyme that converts arachidonic acid to prostaglandins (PGs) and exists in two isoforms, COX-1 and COX-2. In the rodent, increased uterine vascular permeability at sites of blastocyst apposition is one of the earliest prerequisite events in the implantation process. This event is preceded by generalized uterine edema and luminal closure, and coincides with the initial attachment reaction between the trophectoderm and luminal epithelium. Vasoactive PGs are implicated in these processes. Here we demonstrate that COX genes are differentially regulated in the peri-implantation mouse uterus. During the preimplantation period (days 1-4), the COX-1 gene was expressed in the uterine epithelium mainly on day 4 until the initiation of attachment reaction in the evening after which the expression was downregulated. This COX-1 expression coincides with the generalized uterine edema required for luminal closure. In contrast, the COX-2 gene was expressed in the luminal epithelium and subepithelial stromal cells at the anti-mesometrial pole exclusively surrounding the blastocyst at the time of attachment reaction on day 4 and persisted through the morning of day 5. This uterine gene was not expressed at the sites of blastocyst apposition during progesterone (P-4)-treated delayed implantation, but was readily induced in the uterus surrounding the activated blastocysts after termination of the delay by estradiol-17 beta (E(2)). The results suggest that PG synthesis catalyzed by COX-2 is important for localized increased uterine vascular permeability and attachment reaction. The COX-1 gene that was downregulated from the time of attachment reaction on day 4 was again expressed in the mesometrial and anti-mesometrial secondary decidual beds on days 7 and 8. These results suggest that PGs generated by COX-1 are involved in decidualization and/or continued localized endometrial vascular permeability observed during this period. In contrast, the COX-2 gene, expressed at the anti-mesometrial pole on days 4 and 5, switched its expression to the mesometrial pole from day 6 onward. These results suggest that PGs produced at this site by COX-2 are involved in angiogenesis for the establishment of placenta. In the ovariectomized mice, the COX-1 gene was induced in the epithelium by a combined treatment with P-4 and E(2). However, P-4 and/or E(2) treatments failed to influence the uterine COX-2 gene. Overall, the results suggest that the uterine COX-1 gene is influenced by ovarian steroids, while the COX-2 gene is regulated by the implanting blastocyst during early pregnancy.