Polan M L, Simón C, Frances A, Lee B Y, Prichard L E
Department of Gynecology and Obstetrics, Stanford University School of Medicine, CA 94305-5317, USA.
Hum Reprod. 1995 Dec;10 Suppl 2:22-9. doi: 10.1093/humrep/10.suppl_2.22.
Implantation biology is now at a stage where experimental science will be very productive in answering basic questions about the ability of an embryo to implant. The advancement of our knowledge of cytokines and growth factors has been critically important in fuelling the recent new understanding of embryo implantation. Specifically, our increased knowledge of the interleukin (IL)-1 system, as well as leukaemia-inhibiting factor (LIF), epidermal growth factor and colony-stimulating factor-1, and the availability of recombinant protein, specific antibodies and knockout mice, have led to a more detailed outline of implantation events. LIF and IL-1 are the two systems where recent advances have suggested their importance in implantation events. Recently, LIF has been shown in mice to be an endometrial requirement for implantation and embryo development. Although LIF is a pleiotropic molecule, with many interactions in multiple body tissues, in the uterus, concentrations are elevated on day 4 of pregnancy. Experiments with knockout mice have shown the requirement for endometrial LIF for successful implantation. The IL-1 system, consisting of two agonists (IL-1 alpha and IL-1 beta), two receptors (IL-1R types I and II) and the homologous IL-1 receptor antagonist (ra), has also been studied. Knowledge that the embryo secretes IL-1 suggested the interaction between embryonic IL-1 and endometrial receptor, which has been shown to occur. IL-1R type I is plentiful on endometrial epithelial cells and appears to interact with embryonically secreted IL-1 beta to favour implantation. Such implantation events in vivo in mice are blocked by the introduction of large quantities of IL-1ra, consistent with the hypothesis that appropriate interactions between agonist and receptor at the level of the endometrial surface are a requisite for successful implantation. As more specific information on each cytokine or growth factor system comes to light, more complete information on the multiple molecular steps of implantation will become apparent. However, it is clear that no single cytokine or growth factor will be able to explain the complicated events of embryo implantation. Such an important necessary phenomenon has multiple redundancies. The interactions between cytokines and growth factors are becoming increasingly apparent and will need more experimental evidence before a full understanding of implantation is available.
实验科学在回答有关胚胎植入能力的基本问题方面将非常有成效。细胞因子和生长因子知识的进步对于推动近期对胚胎植入的新认识至关重要。具体而言，我们对白介素（IL）-1系统、白血病抑制因子（LIF）、表皮生长因子和集落刺激因子-1的了解不断增加，以及重组蛋白、特异性抗体和基因敲除小鼠的可得性，使得植入事件的轮廓更加详细。LIF和IL-1是两个近期进展表明其在植入事件中具有重要性的系统。最近，在小鼠中已表明LIF是植入和胚胎发育的子宫内膜必需条件。尽管LIF是一种多效性分子，在多个身体组织中有许多相互作用，但在子宫中，其浓度在妊娠第4天升高。基因敲除小鼠实验表明，子宫内膜LIF是成功植入所必需的。由两种激动剂（IL-1α和IL-1β）、两种受体（I型和II型IL-1R）和同源IL-1受体拮抗剂（ra）组成的IL-1系统也已得到研究。胚胎分泌IL-1这一认识提示了胚胎IL-1与子宫内膜受体之间的相互作用，现已证明这种相互作用确实发生。I型IL-1R在子宫内膜上皮细胞中大量存在，似乎与胚胎分泌的IL-1β相互作用以促进植入。在小鼠体内引入大量IL-1ra会阻断此类植入事件，这与以下假设一致：在子宫内膜表面水平上激动剂与受体之间的适当相互作用是成功植入的必要条件。随着关于每种细胞因子或生长因子系统的更具体信息的揭示，关于植入多个分子步骤的更完整信息将变得明显。然而，很明显，没有单一的细胞因子或生长因子能够解释胚胎植入的复杂事件。这样一个重要的必要现象存在多种冗余。细胞因子和生长因子之间的相互作用越来越明显，在全面了解植入之前还需要更多的实验证据。
