Impact of maternal circulating cholesterol and gestational diabetes mellitus on lipid metabolism in human term placenta.
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.
Marseille-Tremblay
Charles
C
Laboratoire de Physiologie Materno-Foetale, Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Quebec, Canada.
Ethier-Chiasson
Maude
M
Forest
Jean-Claude
JC
Giguère
Yves
Y
Masse
André
A
Mounier
Catherine
C
Lafond
Julie
J
D000328:Adult; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood*; D016640:Diabetes, Gestational / Q000097:blood* / Q000235:genetics / Q000378:metabolism*; D054890:Fatty Acid Synthase, Type I / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007231:Infant, Newborn; D050356:Lipid Metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D047929:Term Birth
D012333:RNA, Messenger; C497387:SREBF1 protein, human; C497390:SREBF2 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I