Attempts to Identify Monokine-Like Substances Which Induce Cell Proliferation in the Ectoplacental Cone of Mouse Embryos

基于我们自己在大鼠和小鼠中的观察，我们提出巨噬细胞可能在功能上参与真兽目哺乳动物围产期期间的胚母相互作用（Tachi et al.，1981年，1986年）。近年来，人们对吞噬细胞在妊娠早期可能发挥的作用产生了很大的兴趣。我们改进了体外培养巨噬细胞的方法（Tachi，1988），同时开发了一种适合于定量分析的体外培养小鼠囊胚的新方法（Tachi，1991，1992）。使用这些方法，我们发现巨噬细胞条件培养基高度刺激培养的胚泡的外胎盘锥（以下为EPC）中的细胞增殖（Tachi，1991）。巨噬细胞条件培养基中所含的有效物质的分子量可能低于30，000，并且不同于EGF或FGF。据报道，IGF-1刺激从妊娠10.5天的小鼠分离的胎盘的EPC细胞的增殖（Kanai-Azuma，1992）。然而，IGF-1对培养囊胚EPC细胞的影响目前尚不明显。当本研究项目正在进行时，GM-CSF（Athanassakis等人，1991）和IL-3（Mori等人，1992）刺激EPC细胞增殖。此外，发现M-CSF通过介导子宫内膜中的某些关键过程在小鼠胚胎的植入中起重要作用（Pollard et al.，1992年）。由于IL-3、GM-CSF和M-CSF是众所周知的单核因子，可以说单核因子在鼠科啮齿动物着床中的重要性在文献中逐渐阐明。尽管无法最终确定巨噬细胞条件培养基中物质的分子性质，但我们实验室的研究工作仍在继续。

We proposed on the basis of our own observations in rats and mice that macrophages may be functionally involved in the embryomaternal interactions during the peri-nidatory period in eutherian mammals (Tachi et al., 1981, 1986). Recently, much interest has been focused upon the possible role played by the phagocytes during early gestation. We improved method for the culture of macrophages in vitro (Tachi, 1988), and, at the same time, developed a new method for culture of mouse blastocysts in vitro suitable for quantitative analysis (Tachi, 1991, 1992). Using these methods we found that the macrophage-conditioned medium stimulate highly the proliferation of cells in the ectoplacental cone (EPC in the following) of the cultured blastocysts (Tachi, 1991). The effective substance(s) contained in the macrophage-conditioned medium is probably below 30,000 in molecular weight, and differ from EGF or FGF. It was reported that IGF-1 stimulates the proliferation of EPC cells of the placenta isolated from mice of 10.5 Day of pregnancy (Kanai-Azuma, 1992). However, the effects of IGF-1 on the EPC cells of the cultured blastocysts are at present not so conspicuous. While the present research projects were in progress, GM-CSF (Athanassakis et al., 1991) and IL-3 (Mori et al., 1992) were reported to stimulate the EPC cell proliferation. Furthermore, M-CSF were found to play important roles in implantation of mouse embryos, by mediating certain crucial processes in the endometrium (Pollard et al., 1992). Since IL-3, GM-CSF and M- CSF are well know monokines, it may be said that the importance of the monokines in the implantation of muridae rodents are being gradually elucidated in the literature. Although it was not possible to finally identify the molecular nature of the substance(s) in the macrophage-conditioned medium, the research efforts are still continued in our laboratory.