Greenwood J D, Minhas K, di Santo J P, Makita M, Kiso Y, Croy B A
Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, Ontario, N1G 2W1, Canada.
Placenta. 2000 Sep;21(7):693-702. doi: 10.1053/plac.2000.0556.
Implantation sites from three strains of immunodeficient mice [tgepsilon26, IL-2Rbeta nullxp56(lck)null and IL-2Rgamma null, now known as common cytokine chain gamma (gamma(c)) null], which lack uterine natural killer (uNK) cells, are histologically abnormal. The related anomalies (found from day 10 of gestation) include the absence of aggregation of lymphocytes in the mesometrial triangle, acellularity of the mesometrial decidua, decidual arteries with relatively thick walls and reduced lumen diameters, unusual prominence of the endothelium in the major decidual vessels, and an overall reduction in placental size. In this study we have characterized implantation sites in a new mouse strain (gammac(-)/RAG2(-)) that is deficient in all lymphoid lineages. We have compared implantation sites in tgepsilon26 to gammac(-)/RAG2(-)at the ultrastructural level in order to determine the earliest-time point at which implantation sites differed from those in immunocompetent mice, and the cell types affected. Implantation sites from both the uNK cell-deficient mice resemble those from random-bred, immunocompetent mice on days 6 and 7 of gestation. On day 8 of gestation, decidual cells on the mesometrial sides of implantation sites in both tgepsilon26 and gammac(-)/RAG2(-)revealed pleotrophic morphology and degeneration. In some vessels, endothelial cells were distorted or displaced from their supporting cells. Progressive changes, suggestive of loss of function of both the mesometrial decidua and endothelial cells, were seen to day 14 of gestation, the latest time-point analysed. In contrast to tgepsilon26 mice, homozygously-mated gammac(-)/RAG2(-)had normal litter sizes, with birthweights and weaning weights similar to congenic C57Bl/6J controls, and no significant perinatal loss. In both strains, the newly-documented endothelial cell lesions predict detrimental alterations to vasomotor function of the uterine vasculature. These studies add strength to the hypothesis that uNK cells may have specialized physiological, rather than classically immune, functions in the pregnant mammalian uterus.
三种免疫缺陷小鼠品系[tgepsilon26、IL-2Rβ基因敲除xp56(lck)基因敲除和IL-2Rγ基因敲除，现称为共同细胞因子链γ(γ(c))基因敲除]的着床部位，缺乏子宫自然杀伤(uNK)细胞，组织学上异常。相关异常(从妊娠第10天开始发现)包括子宫系膜三角区淋巴细胞聚集缺失、子宫系膜蜕膜无细胞、子宫系膜蜕膜动脉壁相对增厚且管腔直径减小、主要蜕膜血管内皮异常突出以及胎盘大小整体减小。在本研究中，我们对一种新的小鼠品系(gammac(-)/RAG2(-))的着床部位进行了特征描述，该品系缺乏所有淋巴谱系。我们在超微结构水平上比较了tgepsilon26和gammac(-)/RAG2(-)的着床部位，以确定着床部位与免疫 competent小鼠的着床部位最早出现差异的时间点以及受影响的细胞类型。两种uNK细胞缺陷小鼠的着床部位在妊娠第6天和第7天与随机繁殖的免疫 competent小鼠的着床部位相似。在妊娠第8天，tgepsilon26和gammac(-)/RAG2(-)着床部位子宫系膜侧的蜕膜细胞呈现多形性形态和退变。在一些血管中，内皮细胞从其支持细胞中扭曲或移位。到妊娠第14天(分析的最晚时间点)，可见提示子宫系膜蜕膜和内皮细胞功能丧失的渐进性变化。与tgepsilon26小鼠不同，纯合交配的gammac(-)/RAG2(-)产仔数正常，出生体重和断奶体重与同基因C57Bl/6J对照相似，且无明显围产期损失。在这两种品系中，新记录的内皮细胞病变预示着子宫血管舒缩功能的有害改变。这些研究进一步支持了uNK细胞在妊娠哺乳动物子宫中可能具有特殊生理功能而非经典免疫功能的假说。
