Evidence for Immune Cell Involvement in Decidual Spiral Arteriole Remodeling in Early Human Pregnancy
Evidence for Immune Cell Involvement in Decidual Spiral Arteriole Remodeling in Early Human Pregnancy
复制标题
DOI：
10.2353/ajpath.2009.080995
复制
发表时间：
2009-05-01
影响因子：
6
通讯作者：
Jones, Rebecca L.
中科院分区：
文献类型：
--
作者：
Smith, Samantha D.;Dunk, Caroline E.;Jones, Rebecca L.
蜕膜动脉重塑对于健康妊娠至关重要。这个过程涉及血管平滑肌细胞和内皮细胞的损失，这些细胞和内皮细胞被纤维蛋白样中嵌入的血管内滋养层细胞（vEVT）所取代。先兆子痫是一种导致孕产妇和胎儿死亡和发病的妊娠疾病，重塑过程受到损害。早期血管变化发生在没有 vEVT 的情况下，表明另一种细胞类型参与其中；来自动物模型的证据表明蜕膜白细胞发挥了作用。我们假设白细胞通过触发细胞凋亡或细胞外基质降解参与重塑。通过免疫组织化学检查基底蜕膜样本（妊娠 8 至 12 周），以阐明白细胞、vEVT 和关键重塑事件之间的关联。确定了重塑的独立于滋养层和依赖于滋养层的阶段。基于形态属性的组合，血管轮廓被分为四个阶段的假定时间序列。在重塑的早期阶段，血管平滑肌细胞在 vEVT 出现之前表现出剧烈的破坏和混乱。白细胞（被鉴定为子宫自然杀伤细胞和巨噬细胞）明显浸润血管平滑肌细胞层，并且基质金属蛋白酶-7和-9免疫阳性。一部分血管平滑肌细胞和内皮细胞末端脱氧核苷酸转移酶dUTP缺口末端标记呈阳性，表明重塑涉及细胞凋亡。因此，我们证实血管重塑发生在不同的滋养层非依赖性和依赖性阶段，并提供了蜕膜白细胞参与滋养层非依赖性阶段的第一个证据。 （Am J Pathol 2009，174：1959-1971；DOI：10.2353/ajpath.2009.080995）
Decidual artery remodeling is essential for a healthy pregnancy. This process involves loss of vascular smooth muscle cells and endothelium, which are replaced by endovascular trophoblasts (vEVTs) embedded in fibrinoid. Remodeling is impaired during pre-eclampsia, a disease of pregnancy that results in maternal and fetal mortality and morbidity. Early vascular changes occur in the absence of vEVTs, suggesting that another cell type is involved; evidence from animal models indicates that decidual leukocytes play a role. We hypothesized that leukocytes participate in remodeling through the triggering of apoptosis or extracellular matrix degradation. Decidua basalis samples (8 to 12 weeks gestation) were examined by immunohistochemistry to elucidate associations between leukocytes, vEVTs, and key remodeling events. Trophoblast-independent and -dependent phases of remodeling were identified. Based on a combination of morphological attributes, vessel profiles were classified into a putative temporal series of four stages. in early stages of remodeling, vascular smooth muscle cells showed dramatic disruption and disorganization before vEVT presence. Leukocytes (identified as uterine natural killer cells and macrophages) were apparent infiltrating vascular smooth muscle cells layers and were matrix metalloproteinase-7 and -9 immunopositive. A proportion of vascular smooth muscle cells and endothelial cells were terminal deoxynucleotidyl transferase dUTP nick-end labeling positive, suggesting remodeling involves apoptosis. We thus confirm that vascular remodeling occurs in distinct trophoblast-independent and -dependent stages and provide the first evidence of decidual leukocyte involvement in trophoblast-independent stages. (Am J Pathol 2009, 174:1959-1971; DOI: 10.2353/ajpath.2009.080995)