Effect of Maternal Obesity in Mice on IL-6 Levels and Placental Endothelial Cell Homeostasis.
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.
['Kretschmer|Tobias|T|', 'Schulze-Edinghausen|Merle|M|', 'Turnwald|Eva-Maria|EM|', 'Janoschek|Ruth|R|', 'Bae-Gartz|Inga|I|', 'Zentis|Peter|P|', 'Handwerk|Marion|M|', 'Wohlfarth|Maria|M|', 'Schauss|Astrid|A|', 'Hucklenbruch-Rother|Eva|E|', 'Dötsch|Jörg|J|', 'Appel|Sarah|S|']
D000273:Adipose Tissue D000818:Animals D018929:Cell Culture Techniques D016922:Cellular Senescence D059305:Diet, High-Fat D004195:Disease Models, Animal D042783:Endothelial Cells D005260:Female D005333:Fetus D006706:Homeostasis D015850:Interleukin-6 D051379:Mice D008810:Mice, Inbred C57BL D000079262:Obesity, Maternal D010920:Placenta D011247:Pregnancy
pregnancy human placental vein endothelial cells IL-6-induced senescence epigonadal white adipose tissue inflammation placental dysfunction placental vascular insufficiency pregnancy outcomes