Abstract
The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22–24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000 UI of α-tocopherol/kg) of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%). In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition.
Highlights
In the last decades, the influence of the intrauterine development on the susceptibility to cardiovascular disease has been demonstrated both in humans and in experimental animal models
Our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition
This study reported the involvement of oxidative stress in fetal atherosclerosis, as lesions were significantly reduced when pregnant females were fed with vitamin E-supplemented hypercholesterolemic diets
Summary
The influence of the intrauterine development on the susceptibility to cardiovascular disease has been demonstrated both in humans and in experimental animal models. Additional studies showed that, beyond a caloric restriction, other intrauterine suboptimal conditions, such as excessive nutrient availability or exposure to pollutants, alcohol, or nicotine, can increase the susceptibility of the adult offspring to cardiovascular disease (reviewed in [2]). Maternal adverse conditions can affect embryos at different stages of gestation, even before implantation. Mammalian preimplantation embryos from different animal models, ranging from mice to sheep, are sensitive to environmental factors during the periconceptional period. Exposure of blastocysts to suboptimal conditions both in vivo (i.e., maternal undernutrition) and in vitro
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