Basak Sayantani, Dhar Ruby, Das Chandana
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India.
Biol Reprod. 2002 Jun;66(6):1784-9. doi: 10.1095/biolreprod66.6.1784.
Blastocyst implantation and successful establishment of pregnancy require delicate interactions between the embryo and the maternal uterine milieu, which are controlled at the embryo-maternal interface by the coordinated interplay of a variety of growth factors, cytokines, hormones, and cell adhesion molecules expressed by both the decidualized endometrium and the trophoblast cells. Proper implantation of the embryo is solely dependent on the initial endometrial receptivity and the preparation of the blastocyst to glue itself to the uterine wall. Both these events are considered to be mediated by cell adhesion molecules and integrins expressed by the blastocyst as well by as the maternal endometrium. Integrin expression by the blastocyst and the uterus is a dynamic process. However, reports on the expression and the hormonal modulation of integrins and their role in blastocyst activation and uterine receptivity during implantation are meager. The present study investigates the expression and hormonal regulation of alpha4beta1 integrin by steroid hormones in the blastocyst and the receptive uterus using an in vivo, delayed-implantation mouse model system. The dormant and activated blastocysts as well as the uteri were recovered from ovariectomized mice after progesterone-alone and progesterone-plus-estrogen therapy, respectively. Immunolocalization of protein expression of alpha4 and beta1 integrin subunits indicate that steroids modulate the expression of alpha4beta1 integrin receptor in the mouse blastocyst as well as the uterus and that a differential expression is observed with exposure to progesterone and estrogen. Intrauterine blocking of alpha4 integrin by specific antibody resulted in implantation failure in normal as well as in delayed-implantation mice. Based on our data, we propose here, to our knowledge for the first time, that alpha4beta1 integrin, which is responsible for binding to fibronectin and vascular cell adhesion molecule-1, is induced by estradiol and is down-regulated by progesterone in mice during implantation. Furthermore, the results also indicate the direct role of alpha4 integrin in the process of implantation.
囊胚着床和成功妊娠需要胚胎与母体子宫环境之间的微妙相互作用，这些相互作用在胚胎 - 母体界面由蜕膜化子宫内膜和滋养层细胞表达的多种生长因子、细胞因子、激素和细胞粘附分子的协同作用所控制。胚胎的正确着床仅取决于最初的子宫内膜容受性以及囊胚将自身粘附于子宫壁的准备情况。这两个事件都被认为是由囊胚以及母体子宫内膜表达的细胞粘附分子和整合素介导的。囊胚和子宫中整合素的表达是一个动态过程。然而，关于整合素的表达、激素调节及其在着床期间囊胚激活和子宫容受性中的作用的报道却很少。本研究使用体内延迟着床小鼠模型系统，研究类固醇激素对囊胚和容受性子宫中α4β1整合素的表达和激素调节。分别在单独使用孕酮和孕酮加雌激素治疗后，从去卵巢小鼠中回收休眠和激活的囊胚以及子宫。α4和β1整合素亚基蛋白表达的免疫定位表明，类固醇调节小鼠囊胚和子宫中α4β1整合素受体的表达，并且在暴露于孕酮和雌激素时观察到差异表达。用特异性抗体在子宫内阻断α4整合素导致正常小鼠以及延迟着床小鼠着床失败。基于我们的数据，据我们所知，我们首次提出，负责与纤连蛋白和血管细胞粘附分子 -1结合的α4β1整合素在小鼠着床期间由雌二醇诱导并被孕酮下调。此外，结果还表明α4整合素在着床过程中的直接作用。
