Abstract
Maternal metabolic diseases increase offspring risk for low birth weight and cardiometabolic diseases in adulthood. Excess fructose consumption may confer metabolic risks for both women and their offspring. However, the direct consequences of fructose intake per se are unknown. We assessed the impact of a maternal high-fructose diet on the fetal-placental unit in mice in the absence of metabolic syndrome and determined the association between maternal serum fructose and placental uric acid levels in humans. In mice, maternal fructose consumption led to placental inefficiency, fetal growth restriction, elevated fetal serum glucose and triglyceride levels. In the placenta, fructose induced de novo uric acid synthesis by activating the activities of the enzymes AMP deaminase and xanthine oxidase. Moreover, the placentas had increased lipids and altered expression of genes that control oxidative stress. Treatment of mothers with the xanthine oxidase inhibitor allopurinol reduced placental uric acid levels, prevented placental inefficiency, and improved fetal weights and serum triglycerides. Finally, in 18 women delivering at term, maternal serum fructose levels significantly correlated with placental uric acid levels. These findings suggest that in mice, excess maternal fructose consumption impairs placental function via a xanthine oxidase/uric acid-dependent mechanism, and similar effects may occur in humans.
Highlights
We have little understanding of how fructose intake during pregnancy affects placental function and fetal development
We previously demonstrated that consumption of a high-fructose diet (HFrD) led to impaired glucose tolerance but not weight gain, insulin resistance, or triglyceridemia in pseudo-pregnant C57BL6 female mice[25]
HFrD feeding in mice led to only a few features of metabolic syndrome with no gross dietary deficiencies, protein
Summary
We have little understanding of how fructose intake during pregnancy affects placental function and fetal development. The deleterious effects of fructose do occur in the absence of excess energy intake in mice[20]. We recently showed that in C57BL6 mice, exposure to a high-fructose diet conferred few of the phenotypes associated with metabolic syndrome[25] but did lead to smaller litter sizes, which was, at least in part, due to a defect in decidualization. This model allows us to investigate the effects of a high-fructose diet on reproductive outcomes without confounding by the full metabolic syndrome. To assess human relevance of our mouse data, we examined the association between maternal serum fructose and placental uric acid in a small cohort of women delivering at term by cesarean
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