Prolonged maternal vitamin C deficiency overrides preferential fetal ascorbate transport but does not influence perinatal survival in guinea pigs

Abstract

Human and guinea pig fetuses are completely dependent on an adequate maternal vitamin C (vitC) intake. Shortage of micronutrients can have negative implications for fetal health and pregnancy outcome; however, knowledge of maternal vitC deficiency's impact on fetal development is sparse and reports of pregnancy outcome have been divergent. The present study investigated whether maternal vitC deficiency affects pregnancy outcome and plasma vitC distribution between the mother and the offspring in a guinea pig model. A total of eighty pregnant Dunkin Hartley guinea pigs were randomised into two weight-stratified groups receiving either a deficient (100 mg/kg DEF) or a control (923 mg/kg CTRL) diet. VitC levels were measured in plasma during pregnancy and postpartum, and in the plasma and brain of newborns. Pregnancy outcome was recorded with respect to birth weight and perinatal survival and were similar between groups. Plasma vitC in dams declined throughout gestation in both groups (P,0·01). Compared with maternal plasma vitC, plasma vitC of newborn pups was found to be significantly lower in the DEF group (P, 0·001) and higher in the CTRL group (P,0·001), respectively. Brain vitC levels were significantly reduced in DEF newborn pups (P,0·001). The present results indicate that preferential transport of vitC from the mother to the fetus is overridden during sustained maternal vitC deficiency, maintaining maternal vitC concentration at the expense of the offspring. This contradicts the notion that a fetus is protected from vitC deficiency by the placental Na-dependent vitC co-transporter, SVCT2, thus fetal development may be susceptible to the negative effects of maternal vitC deficiency.

Chronic Vitamin C Deficiency Promotes Redox Imbalance in the Brain but Does Not Alter Sodium-Dependent Vitamin C Transporter 2 Expression

“…As expected, deficient animals had significantly lower levels of VitC in plasma while VitC levels did not differ between CTRL and REPL groups in spite of the difference in VitC status of their mothers (data not shown) [34]. DEF animals also showed increased oxidative stress measured by ascorbate oxidation (%DHA) and MDA.…”

The epigenetic role of vitamin C in health and disease

“…The prevalence of ascorbate deficiency (< 22.7 μM) can be as high as 30.8% in pregnant women during the later pregnancy terms [91]. The maternal deficiency in ascorbate leads to fetal ascorbate deficiency, which could disrupt prenatal development [122], suggesting that ascorbate supplementation might be necessary for pregnant women. It is worth noting that ascorbate supplementation in pregnant women should be aimed at satisfying the needs of TETs and other Fe 2+ and 2OG-dependent dioxygenases in both the mother and the fetus.…”

Does Vitamin C Deficiency Affect Cognitive Development and Function?

“…Importantly, HIF-1α is involved in neuronal development, oxygen homeostasis and angiogenesis including vascular endothelial growth factor and erythropoetin [79,80,81,82]. Regulation of HIF is associated with VitC dependent hydroxylation and subsequent degradation, thus deficiency may increase HIF-1α levels hereby disturbing normal vascular development, likely to be particularly important in the growing fetus and in cases of regeneration following brain injury [51,52,83,84,85]. …”