Sharkey A
Department of Obstetrics and Gynaecology, University of Cambridge, Rosie Maternity Hospital, UK.
Rev Reprod. 1998 Jan;3(1):52-61. doi: 10.1530/ror.0.0030052.
There is strong evidence that cytokines and growth factors play an important role as local mediators of the actions of steroids on the endometrium to prepare it for implantation. These factors have also been shown to act in both an autocrine and paracrine manner to regulate the development of preimplantation embryos in several species. Attempts to define the function of each cytokine have involved receptor localization, establishment of the mode of control by steroid hormones, and functional assays in vivo and in vitro. However, because of the complex and redundant nature of cytokine networks, defining which of this plethora of factors plays a critical role in implantation has proved difficult. Although the development of preimplantation embryos can be influenced directly by cytokines, the in vitro culture of embryos from several species in defined media indicates that exogenous cytokines are not essential for development to the blastocyst stage. Nonetheless, supplementation of media with growth factors may prove valuable in overcoming the detrimental effects of embryo culture in vitro, which is widely used in assisted reproduction techniques in humans and domestic species. The creation of mouse strains in which specific genes for growth factors or adhesion molecules are deleted has also proved important in defining factors essential in implantation, as well as those that play a less significant role. Mice unable to express leukaemia inhibitory factor in the endometrium fail to support implantation, indicating a critical role for this protein in producing a receptive endometrium. Conversely, mouse embryos of the CF-1 strain, which lack the receptor for epidermal growth factor, fail to attach, indicating that this receptor is necessary for producing an implantation competent embryo. It is likely that abnormal expression of such receptors or their ligands in the endometrium underlies some forms of human infertility. Examining the actions of these factors in the endometrium will allow dissection of the molecular basis of embryo attachment and implantation.
有强有力的证据表明，细胞因子和生长因子作为类固醇作用于子宫内膜以使其为着床做好准备的局部介质发挥着重要作用。这些因子还被证明以自分泌和旁分泌方式调节几种物种着床前胚胎的发育。试图确定每种细胞因子的功能涉及受体定位、类固醇激素控制模式的建立以及体内和体外功能测定。然而，由于细胞因子网络的复杂性和冗余性，证明在众多这些因子中哪些在着床中起关键作用是困难的。尽管着床前胚胎的发育可直接受细胞因子影响，但在特定培养基中对几种物种胚胎进行体外培养表明，外源性细胞因子对于发育到囊胚阶段并非必不可少。尽管如此，在培养基中补充生长因子可能被证明对克服体外胚胎培养的有害影响有价值，体外胚胎培养在人类和家畜的辅助生殖技术中广泛使用。创建缺失生长因子或黏附分子特定基因的小鼠品系，在确定着床所必需的因子以及那些作用较小的因子方面也已证明很重要。子宫内膜中无法表达白血病抑制因子的小鼠无法支持着床，表明该蛋白在产生接受性子宫内膜方面起关键作用。相反，缺乏表皮生长因子受体的CF - 1品系小鼠胚胎无法附着，表明该受体对于产生有能力着床的胚胎是必需的。子宫内膜中此类受体或其配体的异常表达很可能是某些形式人类不孕症的基础。研究这些因子在子宫内膜中的作用将有助于剖析胚胎附着和着床的分子基础。
