Abstract
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.
Highlights
Maternal obesity during pregnancy is a major risk factor for the health of mother and child.Multiple cohort studies exist, demonstrating that the incidence of developing pregnancy associatedNutrients 2020, 12, 296; doi:10.3390/nu12020296 www.mdpi.com/journal/nutrientsNutrients 2020, 12, 296 diseases, e.g., gestational diabetes, preeclampsia, and thromboembolytic complications is increased [1], while the fetus is more endangered of being affected by, e.g., growth abnormalities, such as large for gestational age and small for gestational age (LGA and SGA) [2,3] and stillbirth [4]
Disturbed placental development and function leads to an imbalance in fetal supply, thereby most likely causing the known fetal complications connected to maternal obesity
We aimed to investigate the effect of maternal obesity induced by a high fat diet (HFD) on placental vascularization, endothelial cells (EC) homeostasis, and proposed that IL-6 causes EC damage leading to placental insufficiency
Summary
Maternal obesity during pregnancy is a major risk factor for the health of mother and child.Multiple cohort studies exist, demonstrating that the incidence of developing pregnancy associatedNutrients 2020, 12, 296; doi:10.3390/nu12020296 www.mdpi.com/journal/nutrientsNutrients 2020, 12, 296 diseases, e.g., gestational diabetes, preeclampsia, and thromboembolytic complications is increased [1], while the fetus is more endangered of being affected by, e.g., growth abnormalities, such as large for gestational age and small for gestational age (LGA and SGA) [2,3] and stillbirth [4]. Maternal obesity during pregnancy is a major risk factor for the health of mother and child. Multiple cohort studies exist, demonstrating that the incidence of developing pregnancy associated. Children exposed to maternal obesity during pregnancy are more likely to develop obesity, diabetes, and other related diseases in later life [5]. Many studies are trying to explain how and why maternal obesity leads to the pregnancy complications described above, often speculating about a dysfunctional placenta. The placenta is the central organ during pregnancy, connecting mother and fetus, providing the fetus with nutrients, oxygen, various hormones, and other important factors. Disturbed placental development and function leads to an imbalance in fetal supply, thereby most likely causing the known fetal complications connected to maternal obesity
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