Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Strasse 62, 50937 Cologne, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Robert-Koch-Strasse 21, 50931 Cologne, Germany.
Nutrients. 2020 Jan 22;12(2):296. doi: 10.3390/nu12020296.
Obesity during pregnancy is a known health risk for mother and child. Since obesity is associated with increased inflammatory markers, our objectives were to determine interleukin-6 (IL-6) levels in obese mice and to examine the effect of IL-6 on placental endothelial cells. Placentas, blood, and adipose tissue of C57BL/6N mice, kept on high fat diet before and during pregnancy, were harvested at E15.5. Serum IL-6 levels were determined and endothelial cell markers and IL-6 expression were measured by qRT-PCR and western blot. Immunostaining was used to determine surface and length densities of fetal capillary profiles and placental endothelial cell homeostasis. Human placental vein endothelial cells were cultured and subjected to proliferation, apoptosis, senescence, and tube formation assays after stimulation with hyperIL-6. Placental endothelial cell markers were downregulated and the percentage of senescent endothelial cells was higher in the placental exchange zone of obese dams and placental vascularization was strongly reduced. Additionally, maternal IL-6 serum levels and IL-6 protein levels in adipose tissue were increased. Stimulation with hyperIL-6 provoked a dose dependent increase of senescence in cultured endothelial cells without any effects on proliferation or apoptosis. Diet-induced maternal obesity led to an IUGR phenotype accompanied by increased maternal IL-6 serum levels. In the placenta of obese dams, this may result in a disturbed endothelial cell homeostasis and impaired fetal vasculature. Cell culture experiments confirmed that IL-6 is capable of inducing endothelial cell senescence.
孕期肥胖是母婴健康的已知风险。由于肥胖与炎症标志物的增加有关，我们的目标是确定肥胖小鼠的白细胞介素-6 (IL-6)水平，并研究 IL-6 对胎盘内皮细胞的影响。在怀孕前和怀孕期间，将 C57BL/6N 小鼠饲养在高脂肪饮食中，然后收获 E15.5 时的胎盘、血液和脂肪组织。通过 qRT-PCR 和 Western blot 测定血清 IL-6 水平，并测量内皮细胞标志物和 IL-6 表达。免疫染色用于确定胎儿毛细血管轮廓的表面和长度密度以及胎盘内皮细胞的稳态。培养人胎盘静脉内皮细胞，并在刺激高 IL-6 后进行增殖、凋亡、衰老和管形成测定。肥胖母鼠胎盘交换区的胎盘内皮细胞标志物下调，衰老内皮细胞的百分比更高，胎盘血管化强烈减少。此外，母鼠血清 IL-6 水平和脂肪组织中的 IL-6 蛋白水平增加。高浓度 IL-6 刺激导致培养的内皮细胞衰老呈剂量依赖性增加，而对增殖或凋亡没有任何影响。饮食诱导的母体肥胖导致 IUGR 表型，同时伴有母血清 IL-6 水平升高。在肥胖母鼠的胎盘，这可能导致内皮细胞稳态紊乱和胎儿血管受损。细胞培养实验证实 IL-6 能够诱导内皮细胞衰老。
