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

根据我们在大鼠和小鼠身上的观察，我们提出巨噬细胞可能参与真兽类围产期的胚胎-母体相互作用(Tachi等人，1981,1986)。最近，吞噬细胞在早期妊娠中可能起的作用引起了人们的极大兴趣。我们改进了巨噬细胞体外培养的方法(Tachi，1988)，同时发展了一种新的适合于定量分析的小鼠囊胚体外培养方法(Tachi，1991,1992)。利用这些方法，我们发现巨噬细胞条件培养液高度刺激培养的胚泡外胎盘锥体(下称EPC)细胞的增殖(Tachi，1991)。巨噬细胞条件培养液中含有的有效物质(S)分子量可能小于30,000，不同于表皮生长因子或成纤维细胞生长因子。有报道称，IGF-1可刺激孕10.5天小鼠胎盘EPC细胞的增殖(Kanai-Azuma，1992)。然而，IGF-1对培养的囊胚EPC细胞的作用目前还不是很明显。目前的研究项目正在进行中，有报道称GM-CSF和IL-3能刺激EPC细胞的增殖。此外，M-CSF通过调节子宫内膜中的某些关键过程，在小鼠胚胎着床中发挥重要作用(Pollard等人，1992)。由于IL-3、GM-CSF和M-CSF是众所周知的单因子，可以说，单因子在小鼠着床过程中的重要性正逐渐在文献中阐明。虽然还不可能最终确定巨噬细胞条件培养液中该物质(S)的分子性质，但研究工作仍在我们实验室继续进行。

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.