Early Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis

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.

Blood lipids during pregnancy: A progressively appreciated subject in basic and clinical research

“…On the other hand, supraphysiological changes in blood cholesterol during pregnancy also seem to impact significantly on maternal, fetal, and offspring outcomes [2]. For instance, high LDL-cholesterol during pregnancy has been associated with preterm delivery [2] as well as retarded intrauterine growth [12]. More dramatically, homozygous familial hypercholesterolemia without treatment during pregnancy can be a fatal condition [13].…”

Pre-gestational overweight in guinea pig sows induces fetal vascular dysfunction and increased rate of large and small fetuses

“…On the other hand, in LWF from HWS, the increased brain to liver ratio and the altered umbilical artery Doppler suggest the presence of a fetal growth restriction. This effect could have been unnoticed in the fetal biometry follow-up owing to the inherent limitations of this technique, 21 but it could represent a potential early onset of IUGR as occurs in other models of maternal obesity 15 in which fetal growth could be compromised at embryonic stages. 14 Altogether, this data suggest that pre-gestational overweight in guinea pigs increases the risk of IUGR and macrosomia as occurs in human pregnancies.…”

“…[9][10][11] Interestingly, despite the strong metabolic intervention, maternal obesity in these models associates mainly with intrauterine growth restriction (IUGR) rather than macrosomia, in both mice and rats. [12][13][14][15] Notably, guinea pigs have a spontaneous capacity of becoming obese, which ultimately impacts on their reproductive outcomes. 16 In fact a pre-pregnancy weight over 700 g in guinea pigs sows associates with increased adiposity, reduced fertility and litter size, but apparently increased offspring birth weight.…”

Modulation of cholesterol transport by maternal hypercholesterolemia in human full-term placenta

“…Few studies suggest that maternal contribution can vary with the maternal metabolic environment during pregnancy [ 9 , 17 ]. Therefore, the objectives of the present study were to (1) analyze the impact of maternal hypercholesterolemia on the expression of cholesterol metabolism genes in human term placenta and (2) to evaluate if there is any correlation between maternal/cord serum cholesterol with the expression of theses transporters.…”