Impact of maternal circulating cholesterol and gestational diabetes mellitus on lipid metabolism in human term placenta

Abstract

Maternal hypercholesterolemia (HC) during pregnancy and gestational diabetes mellitus (GDM) are associated with disturbance of fetal development which may also modify key features of placental functions. In this study, we evaluated the impact of maternal hypercholesterolemia on placental cholesterol and lipid metabolism in 59 women classified in two groups according to the median concentration of plasma total cholesterol (6.42 mM). The impact of GDM was also evaluated on the metabolism of placentas obtained from 7 insulin-treated GDM and 7 non-GDM women. We showed that high maternal circulating cholesterol is associated with a significant increase in the LDL-cholesterol, ApoB-100 and triglyceride concentrations in the maternal blood. However the level of cholesterol in the venous cord blood and placenta remains unchanged in response to modification in maternal cholesterol profile. The levels of Fatty acid synthase (FAS) and SREBP-2 expressions in placenta are significantly increased in the HC group while expression of both sterol regulatory element-binding proteins-1 (SREBP-1) and HMG-CoA reductase (HMGR) are not modified. GDM is not associated with modification in the maternal lipid profile but it increases the concentration of inflammatory cytokines (IL-1beta and TNF-alpha) in placenta which correlates with a dramatic induction of FAS expression without affecting the expression of mature SREBPs proteins. In conclusion, our study suggests that in placenta, expressions of key proteins involved in de novo lipid synthesis are affected by changes in maternal metabolism (HC and GDM) that may subsequently affect fetal development.

Maternal Hypercholesterolemia in Pregnancy Associates With Umbilical Vein Endothelial Dysfunction

“…31 Furthermore, increased early atherosclerosis markers, such as fatty streaks and lipid peroxidation, in human fetal aorta 5 or in 7-to 14-year-old children 32 born from mothers with TCh level over this cut-off point is reported. Because TCh, HDL-C, and triglyceride plasma by guest on May 11, 2018 http://atvb.ahajournals.org/ Downloaded from levels were unaltered in newborns from women with MSPH, confirming previous observations, 33,34 we speculate on the possibility that MSPH is a pathological condition of the mother coursing with altered human fetoplacental vasculature. A role for LDL-C is suggested in this phenomenon because its maternal plasma concentration was higher in MSPH compared with MPH and because LDL-C is transferred across the placenta.…”

Normalizing Metabolism in Diabetic Pregnancy: Is It Time to Target Lipids?

“…Similarly, maternal cholesterol has been reported as increased (17) or unchanged (14,18,19) across gestation. Studies in women with GDM have shown no difference (18) or a decline in LDL-C concentration (20) but with increased levels of small, dense LDL (18,20) and increased LDL oxidation (17).…”

Relation between fetal anthropometric parameters and cord blood adiponectin and high-sensitivity C-reactive protein in gestational diabetes mellitus

“…Genes for lipid metabolism and those for inflammatory pathways are upregulated in the placenta of women with GDM (2). This upregulation increases or unbalances production of inflammatory cytokines and energy metabolism regulatory cytokines such as adipokines (2,6,7), which increases adiposity at birth (8,9) and predisposes the newborn to become overweight and develop metabolic diseases such as impaired glucose tolerance, metabolic syndrome, and cardiovascular disease (2,(6)(7)(8). Previous studies have focused on the pathophysiologic pathways and cytokine levels in GDM and their possible effect on offspring comorbidities later in life (1,6,7,10).…”