Khatua Atanu, Wang Xiaohong, Ding Tianbing, Zhang Qian, Reese Jeff, DeMayo Francesco J, Paria Bibhash C
Division of Reproductive and Developmental Biology, D4124 Medical Center North, 1161 21st Avenue South, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2678, USA.
Endocrinology. 2006 Sep;147(9):4079-92. doi: 10.1210/en.2006-0231. Epub 2006 Jun 22.
Implantation occurs only in the progesterone (P4)-primed uterus in the majority of species, but little effort has been given to identify P4-mediated molecules in these species. Using hamsters as a model for P4-dependent implantation and three well-known uterine receptivity-associated P4-regulated genes, Indian hedgehog (Ihh), histidine decarboxylase (Hdc), and amphiregulin (Areg), in mice that require ovarian estrogen for uterine receptivity and implantation, our strategy aimed to determine whether P4 regulates uterine expression of these genes in hamsters and whether the event- and cell-specific uterine expression patterns of these genes during the periimplantation period in hamsters follow similarly with their patterns in mice. We report here that P4-mediated Ihh signaling is important for uterine receptivity and implantation in hamsters because uterine epithelial Ihh expression was regulated by P4 and its expression patterns during the periimplantation period of hamsters closely follow its pattern in mice. In contrast, we noted no hormonal regulation of Hdc and Areg in the hamster uterus. However, this did not diminish their importance in hamsters because their expression patterns and functions are event and cell specific during the periimplantation period: whereas Hdc was expressed exclusively in d 4 uterine glands and regulated by the blastocyst, Areg was expressed on the decidual area adjacent to the embryo from d 5 onward and involved in stromal cell proliferation. We conclude that similarities and dissimilarities exist in uterine expression pattern of implantation-related genes, including hormonal regulation and their event-specific importance.
在大多数物种中,着床仅发生在经孕酮(P4)预处理的子宫中,但在这些物种中,人们很少致力于鉴定P4介导的分子。以仓鼠作为P4依赖型着床的模型,并以三种著名的与子宫接受性相关的P4调控基因,即印度刺猬因子(Ihh)、组氨酸脱羧酶(Hdc)和双调蛋白(Areg)为例,在需要卵巢雌激素来实现子宫接受性和着床的小鼠中,我们的策略旨在确定P4是否调节仓鼠中这些基因的子宫表达,以及在仓鼠着床前期这些基因在事件和细胞特异性的子宫表达模式是否与小鼠中的模式相似。我们在此报告,P4介导的Ihh信号传导对仓鼠的子宫接受性和着床很重要,因为子宫上皮Ihh表达受P4调节,并且在仓鼠着床前期其表达模式与小鼠中的模式密切相关。相比之下,我们注意到仓鼠子宫中Hdc和Areg没有激素调节。然而,这并没有削弱它们在仓鼠中的重要性,因为它们在着床前期的表达模式和功能在事件和细胞上是特异性的:Hdc仅在第4天的子宫腺体中表达并受胚泡调节,而Areg从第5天起在与胚胎相邻的蜕膜区域表达并参与基质细胞增殖。我们得出结论,着床相关基因的子宫表达模式存在异同,包括激素调节及其在事件特异性方面的重要性。