Effect of gestational hypercholesterolaemia on omental vasoreactivity, placental enzyme activity and transplacental passage of normal and oxidised fatty acids

Abstract

Objective Maternal hypercholesterolaemia during pregnancy increases lipid peroxidation in mothers and fetuses and programs increased susceptibility to atherosclerosis later in life. The objective of this study was to elucidate the role of the placenta in mediating oxidative stress from mother to offspring.Design Comparison between normo-and hypercholesterolaemic mothers (n = 36 each) and their children.Setting Obstetric wards, hospitals of the University of Naples and Regione Campania.Population Healthy primiparas delivering by caesarean section.Methods Biochemical measurements of oxidative stress and serum leptin in cord plasma and placenta, immunochemistry of placenta microvessels, and vasoreactivity studies were performed.Main outcome measures Oxidative status (i.e. lipid composition and content of oxidised fatty acids, activity of pro-and antioxidant enzymes, immunohistochemical presence of oxidation-specific epitopes) in maternal and cord blood and in placental tissue, as well as vascular reactivity in omental arteries.Results Hypercholesterolaemia during pregnancy was associated with extensive changes in fatty acid composition of both maternal and cord blood lipids, sufficient to alter vasoreactivity of omental vessels. Results also indicated that the placenta is not only subject to substantial oxidative stress, but that it may further increase fetal oxidative stress through changes of pro-and antioxidant enzyme activities.Conclusions The placenta plays an important role in both transmitting and enhancing pathogenic effects of gestational hypercholesterolaemia.

Maternal Low-Protein Diet or Hypercholesterolemia Reduces Circulating Essential Amino Acids and Leads to Intrauterine Growth Restriction

“…Maternal oxidative stress in a high cholesterol environment may adversely affect the placenta and may directly or indirectly enhance atherosclerotic lesions in the offspring (44). Experiments in hypercholesterolemic rabbits have shown that administration of the antioxidant vitamin E during pregnancy resulted in reduced atherosclerotic lesions in the offspring (16,17), indicating that maternal oxidative stress likely plays a role in maternal programming for atherosclerosis.…”

Maternal Hypercholesterolemia in Pregnancy Associates With Umbilical Vein Endothelial Dysfunction

“…This cut-off point is similar to TCh level in pregnant women showing increased oxidative stress in maternal and fetal blood, and homogenized placenta, and exhibit reduced maternal omental artery reactivity and altered composition of the fetal blood fatty acids. 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.…”

Maternal–Fetal Cholesterol Transport in the Placenta

“…In fact, studies in humans have shown that the placenta is both the target of maternal oxidative stress and a modulator of fetal oxidative stress. 15 Furthermore, extensive data exist on atherogenic programming of arterial endothelial cells by maternal hypercholesterolemia, obesity, the metabolic syndrome, and diabetes. 16,17 It is therefore likely that changes in HPEC signaling are similarly early and extensive.…”