McMaster University Department of Medicine, Health Sciences Center, Room 3H1E, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4K1; Department of Immunology, Faculty of Medicine, and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Toronto General Research Institute, Canada.
J Reprod Immunol. 2014 Jun;103:1-8. doi: 10.1016/j.jri.2014.02.006. Epub 2014 Mar 16.
It has been suggested that the differences between placentation in humans and rodents, such as mice, are sufficient to render human pregnancy unique and to justify ignoring data generated using mice. Detailed examination of the placenta-decidua interaction and decidual NK cell composition in humans, and mice, show that the principles are the same. Indeed, the rat placenta is useful in showing an intermediary arrangement between humans and mice. This is consistent with the thesis of Darwin that structures of older species evolve with development of new species to provide a survival advantage. Molecular details may differ between species, but also between individuals given gene polymorphisms. Human data on interaction of HLA-C2 with NK cell KIR receptors has been used to suggest that human pregnancy problems such as recurrent miscarriage, fetal growth retardation, and pre-eclampsia are due to lack of activation of true uterine NK cell (TuNK) functions that promote trophoblast cell growth and invasion which prevents such problems. But when TuNKs bear certain KIR phenotypes, pathology results. It is shown that such mechanisms could only be pertinent in less than one-third of recurrent miscarriage patients. Activated blood-type NK cells that enter the uterus (BuNKs) remain the major effector of pregnancy loss in humans, and this is consistent with data from the mouse. The importance of activated BuNKs in pre-eclampsia and fetal growth retardation merits further investigation as pre-eclampsia and fetal growth restriction are also manifest in the CBAxDBA/2 mouse model where activated NK cells are the initiator of abortions.
有人认为，人类和啮齿动物（如老鼠）的胎盘存在差异，这足以使人类妊娠具有独特性，并证明忽视使用老鼠产生的数据是合理的。详细研究人类和老鼠的胎盘-蜕膜相互作用和蜕膜 NK 细胞组成表明，其原理是相同的。事实上，大鼠胎盘在展示人类和老鼠之间的中间排列方面很有用。这与达尔文的论点一致，即较老物种的结构随着新物种的发展而进化，以提供生存优势。分子细节可能在物种之间存在差异，但在个体之间也存在差异，因为存在基因多态性。人类关于 HLA-C2 与 NK 细胞 KIR 受体相互作用的数据被用于表明，人类妊娠问题，如反复流产、胎儿生长迟缓、子痫前期等，是由于缺乏真正的子宫 NK 细胞（TuNK）功能的激活，这些功能促进滋养细胞的生长和浸润，从而预防这些问题。但当 TuNK 具有某些 KIR 表型时，就会出现病理。研究表明，这种机制可能只与不到三分之一的反复流产患者有关。进入子宫的激活血型 NK 细胞（BuNKs）仍然是人类妊娠丢失的主要效应物，这与老鼠的数据一致。激活的 BuNKs 在子痫前期和胎儿生长迟缓中的重要性值得进一步研究，因为子痫前期和胎儿生长受限也在 CBAxDBA/2 小鼠模型中表现出来，其中激活的 NK 细胞是流产的启动者。
