Prevention of Teratogenesis in Pregnancies of Obese Rats by Vitamin E Supplementation

Abstract

Congenital malformations are a common adverse outcome in pregnancies complicated by pregestational obesity, although the underlying mechanisms are still unrevealed. Our aim was to study the effect of oxidative stress in obesity-induced teratogenesis. Wistar rats were fed a high-fat diet for 13 weeks, with (OE group) or without (O group) vitamin E supplementation. Then, rats were mated and sacrificed at day 11.5 of gestation. Embryos from O dams presented a 25.9 ± 3.5% rate of malformations (vs. 8.7 ± 3.4% in C rats), which was reduced in the OE group (11.5 ± 2.3%). Pregestational obesity induced hepatic protein and DNA oxidation and a decline in antioxidant enzymes. Importantly, glutathione content was also decreased, limiting the availability of this antioxidant in the embryos. Vitamin E supplementation efficiently maintained glutathione levels in the obese mothers, which could be used in their embryos to prevent oxidation-induced malformations. To test the effect of decreasing glutathione levels alone in a cell culture model of neuroepithelium, murine embryonic stem cells (ESC) were induced to form neuronal precursors and glutathione synthesis was inhibited with the gamma–glutamylcysteine synthesis inhibitor, buthionine sulfoximine (BSO). BSO inhibited the expression of Pax3, a gene required for neural tube closure that is also inhibited by oxidative stress. Taken together, our data indicate that obesity causes malformations through the depletion of maternal glutathione, thereby decreasing glutathione-dependent free radical scavenging in embryos, which can be prevented by vitamin E supplementation.

Generation of Highly Antioxidant Submicron Particles from Myrtus communis Leaf Extract by Supercritical Antisolvent Extraction Process

“…Advanced Oxidation Protein Products (AOPP) are uremic toxins generated as a result of the oxidation of proteins by chlorinated oxidants. The AOPPs in the samples were calorimetrically detected by using potassium iodine in an acid environment, as previously described [46]. The AOPP concentrations were expressed as micromoles of Chloramine-T equivalents per mg of analyzed tissue.…”

The Influence of Methanol Extracts of Some Plant Species Used in the Management of Pregnancy-Related Symptoms on the Reproductive Parameters of Pregnant Wistar Rats

“…Mortality and morbidity were recorded on days 1, 3, 6, 9, 12, and 15. 20 After day 15 of the treatment, the animals were sacrificed under chloroform anaesthesia.…”

Effect of Oxidative Stress on Reproduction and Development

“…Furthermore, embryopathy-susceptible embryos are more prone to induce oxidative stress by high glucose levels. Alcala et al report an interesting study on the effect of oxidative stress in obesity-induced teratogenesis [ 12 ]. The results show that pregestational obesity in rats induces hepatic protein and DNA oxidation and a decline in antioxidant enzymes.…”