Bekker Mireille N, van den Akker Nynke M S, Bartelings Margot M, Arkesteijn Jenny B, Fischer Sigrid G L, Polman Japke A E, Haak Monique C, Webb Sandra, Poelmann Robert E, van Vugt John M G, Gittenberger-de Groot Adriana C
Department of Obstetrics and Gynecology, VU University Medical Center, Amsterdam, The Netherlands.
J Soc Gynecol Investig. 2006 Apr;13(3):209-16. doi: 10.1016/j.jsgi.2006.02.003.
Nuchal edema (NE) is a clinical indicator for aneuploidy, cardiovascular anomalies, and several genetic syndromes. Its etiology, however, is unknown. In the nuchal area, the endothelium of the jugular lymphatic sacs (JLS) develops by budding from the blood vascular endothelium of the cardinal veins. Abnormal distension of the jugular sacs is associated with NE. We hypothesize that a disturbed lymphatic endothelial differentiation and sac formation causes NE. We investigated endothelial differentiation of the jugular lymphatic system in human and mouse species with NE.
Aneuploid human fetuses (trisomy 21; trisomy 18) were compared with euploid controls (gestational age 12 to 18 weeks). Trisomy 16 mouse embryos were compared with wild type controls (embryonic day 10 to 18). Trisomy 16 mice are considered an animal model for human trisomy 21. Endothelial differentiation was investigated by immunohistochemistry using lymphatic markers (prox-1, podoplanin, lymphatic vessel endothelial hyaluronan receptor [LYVE]-1) and en blood vessel markers (neuropilin [NP]-1 and ligand vascular endothelial growth factor [VEGF]-A). Smooth muscle actin (SMA) was included as a smooth muscle cell marker.
We report a disturbed venous-lymphatic phenotype in aneuploid human fetuses and mouse embryos with enlarged jugular sacs and NE. Our results show absent or diminished expression of the lymphatic markers Prox-1 and podoplanin in the enlarged jugular sac, while LYVE-1 expression was normal. Additionally, the enlarged JLS showed blood vessel characteristics, including increased NP-1 and VEGF-A expression. The lumen contained blood cells and smooth muscle cells lined the wall.
A loss of lymphatic identity seems to be the underlying cause for clinical NE. Also, abnormal endothelial differentiation provides a link to the cardiovascular anomalies associated with NE.
颈部水肿（NE）是一种用于提示非整倍体、心血管异常及多种遗传综合征的临床指标。然而，其病因尚不清楚。在颈部区域，颈淋巴囊（JLS）的内皮是由主静脉的血管内皮出芽发育而来。颈淋巴囊的异常扩张与NE有关。我们推测，淋巴内皮细胞分化和囊形成紊乱会导致NE。我们研究了患有NE的人类和小鼠物种颈淋巴系统的内皮分化情况。
将非整倍体人类胎儿（21三体；18三体）与整倍体对照（孕龄12至18周）进行比较。将16三体小鼠胚胎与野生型对照（胚胎第10至18天）进行比较。16三体小鼠被视为人类21三体的动物模型。使用淋巴标志物（Prox-1、足板蛋白、淋巴管内皮透明质酸受体[LYVE]-1）和血管标志物（神经纤毛蛋白[NP]-1和配体血管内皮生长因子[VEGF]-A）通过免疫组织化学研究内皮分化。包括平滑肌肌动蛋白（SMA）作为平滑肌细胞标志物。
我们报告在患有颈淋巴囊增大和NE的非整倍体人类胎儿和小鼠胚胎中存在静脉-淋巴表型紊乱。我们的结果显示，在增大的颈淋巴囊中，淋巴标志物Prox-1和足板蛋白的表达缺失或减少，而LYVE-1表达正常。此外，增大的JLS显示出血管特征，包括NP-1和VEGF-A表达增加。管腔内含有血细胞，壁内衬有平滑肌细胞。
淋巴特性的丧失似乎是临床NE的根本原因。此外，异常的内皮分化为与NE相关的心血管异常提供了联系。
