Morton H, Cavanagh A C, Athanasas-Platsis S, Quinn K A, Rolfe B E
Department of Surgery, University of Queensland, Royal Brisbane Hospital, Australia.
Reprod Fertil Dev. 1992;4(4):411-22. doi: 10.1071/rd9920411.
Early pregnancy factor (EPF) was first described as a pregnancy-associated substance, although recent studies suggest a more general link with cell development. It is a product of actively dividing cells and its apparent functional importance to them suggests its potential as a regulator of cell proliferation. The recent discovery of EPF in platelets has provided a comparatively rich and readily available source of EPF. The purification procedures employed to isolate EPF from this source have also been applied to pregnancy serum and urine, medium conditioned by oestrous mouse ovaries (stimulated with prolactin and embryo-conditioned medium), medium conditioned by tumour cells, and serum from rats 24 h after partial hepatectomy (PH). In all instances, biological activity followed the same pattern throughout. Furthermore, the final active reversed-phase high-performance liquid chromatography fraction from all sources was bound specifically by immobilized anti-EPF monoclonal antibodies (MAbs), indicating that the active fractions produced from these diverse sources are very closely related, if not identical. Some differences have been observed in the behaviour of EPF in various conditions. EPF is produced by proliferating tumour cells and by liver cells post-PH, and passive immunization studies with anti-EPF MAbs have shown that these cells need EPF for survival. In contrast, EPF has not been detected as a product of the pre-embryo, and addition of anti-EPF MAbs to embryo cultures does not adversely affect development from the 2-cell to the blastocyst stage. Although the pre-embryo is not dependent on EPF for its development in vitro, neutralization of EPF in vivo by anti-EPF MAbs retards its development. Thus, EPF appears to play an indirect role in maintaining the pre-embryo. By virtue of its ability to suppress the delayed-type hypersensitivity reaction, it has been suggested that EPF might act as an immunological response modifier of the maternal immune system. Alternatively, the effect of EPF on lymphocytes may be to reduce the expression of all or some cytokines and this could inhibit development. Whether or not EPF acts more directly as an autocrine growth factor from around the time of implantation, when the embryo first begins synthesis of EPF, is not known and remains to be investigated.
早期妊娠因子（EPF）最初被描述为一种与妊娠相关的物质，不过最近的研究表明它与细胞发育存在更广泛的联系。它是活跃分裂细胞的产物，其对这些细胞明显的功能重要性表明它具有作为细胞增殖调节因子的潜力。最近在血小板中发现EPF提供了一个相对丰富且易于获取的EPF来源。用于从该来源分离EPF的纯化程序也已应用于妊娠血清和尿液、经催乳素刺激的动情期小鼠卵巢条件培养基（以及胚胎条件培养基）、肿瘤细胞条件培养基，以及部分肝切除（PH）后24小时大鼠的血清。在所有情况下，生物活性在整个过程中都遵循相同的模式。此外，来自所有来源的最终活性反相高效液相色谱馏分都被固定化抗EPF单克隆抗体（MAbs）特异性结合，这表明从这些不同来源产生的活性馏分即使不完全相同也非常密切相关。在各种条件下观察到了EPF行为的一些差异。EPF由增殖的肿瘤细胞和PH后的肝细胞产生，用抗EPF单克隆抗体进行的被动免疫研究表明这些细胞需要EPF来维持存活。相比之下，尚未检测到EPF是胚前期的产物，并且向胚胎培养物中添加抗EPF单克隆抗体不会对从2细胞期到囊胚期的发育产生不利影响。虽然胚前期在体外发育不依赖于EPF，但抗EPF单克隆抗体在体内中和EPF会阻碍其发育。因此，EPF似乎在维持胚前期方面发挥间接作用。由于其抑制迟发型超敏反应的能力，有人提出EPF可能作为母体免疫系统的免疫反应调节剂发挥作用。或者，EPF对淋巴细胞的作用可能是减少全部或部分细胞因子的表达，这可能会抑制发育。从胚胎开始合成EPF的植入期左右开始，EPF是否更直接地作为自分泌生长因子发挥作用尚不清楚，仍有待研究。
