Lim H, Dey S K
Department of Molecular and Integrative Physiology, Ralph L. Smith Research Center, University of Kansas Medical Center, Kansas City 66160-7336, USA.
Endocrinology. 1997 Nov;138(11):4599-606. doi: 10.1210/endo.138.11.5528.
Among the PGs, PGE2 is considered especially important for implantation and decidualization. Four major PGE2 receptor subtypes, EP1, EP2, EP3, and EP4, mediate various PGE2 effects via their coupling to distinct signaling pathways. Previously, we have shown that the EP1, EP3, and EP4 genes are expressed in the periimplantation mouse uterus in a spatio-temporal manner, suggesting compartmentalized actions of PGE2 during this period. In this study, we examined the expression of the EP2 gene in the mouse uterus during the periimplantation period (days 1-8) and during experimentally induced progesterone (P4)-maintained delayed implantation and its resumption by 17beta-estradiol (E2). We also examined its regulation in the uterus by ovarian steroid hormones. Our results establish that EP2 messenger RNA (mRNA) is expressed exclusively in the luminal epithelium primarily on day 4 (the day of implantation) and day 5 (early implantation) of pregnancy. In (P4)-maintained delayed implanting mice, EP2 mRNA was present in the luminal epithelium, and the expression was further enhanced regardless of the location of the blastocysts after reinitiation of implantation. This observation suggests little or no embryonic influence in regulating EP2 expression and, instead, shows its regulation by P4 and E2. Indeed, treatment with E2 and/or P4 exhibited unique regulation of this gene. The treatment of adult ovariectomized mice with E2 down-regulated the basal levels of EP2 mRNA, whereas that with P4 up-regulated its levels in the luminal epithelium. The up-regulation of EP2 mRNA levels by P4 was further augmented by superimposition of the E2 treatment, suggesting a synergistic interaction between E2 and P4 in regulating this gene in the uterus. Collectively, the results suggest that EP2 could be a potential mediator of PGE2 actions in regulating luminal epithelial differentiation and serve as a marker for uterine receptivity for implantation.
在前列腺素（PGs）中，前列腺素E2（PGE2）被认为对植入和蜕膜化尤为重要。前列腺素E2的四种主要受体亚型，即EP1、EP2、EP3和EP4，通过与不同的信号通路偶联来介导前列腺素E2的各种效应。此前，我们已经表明，EP1、EP3和EP4基因在植入前小鼠子宫中以时空方式表达，这表明在此期间前列腺素E2具有分区作用。在本研究中，我们检测了植入前时期（第1 - 8天）以及实验诱导的孕酮（P4）维持的延迟植入及其通过17β - 雌二醇（E2）恢复过程中小鼠子宫中EP2基因的表达。我们还研究了卵巢甾体激素对子宫中该基因的调控。我们的结果表明，EP2信使核糖核酸（mRNA）仅在妊娠第4天（植入日）和第5天（早期植入）主要在腔上皮中表达。在孕酮维持的延迟植入小鼠中，EP2 mRNA存在于腔上皮中，并且在植入重新启动后，无论囊胚位置如何，其表达都会进一步增强。这一观察结果表明胚胎对EP2表达的调节作用很小或没有，相反，表明其受P4和E2的调节。事实上，用E2和/或P4处理对该基因表现出独特的调控。用E2处理成年去卵巢小鼠会下调EP2 mRNA的基础水平，而用P4处理则会上调其在腔上皮中的水平。E2处理叠加后，P4对EP2 mRNA水平的上调作用进一步增强，这表明E2和P4在调节子宫中该基因方面存在协同相互作用。总体而言，这些结果表明，EP2可能是前列腺素E2调节腔上皮分化作用的潜在介质，并可作为子宫对植入接受性的标志物。
