Recent Studies on Neural Tube Defects in Embryos of Diabetic Pregnancy: An Overview

Abstract

Maternal diabetes develops in 2-6% of total pregnancies, depending on geographical and ethnic background. About 10% of fetuses from diabetic pregnancy display congenital malformations in various organ systems including cardiovascular, gastrointestinal, genitourinary and neurological systems, among which the neural tube defects (NTDs) such as anencephaly, holoprosencephaly and syntelencephaly were more frequently demonstrated. Recent studies by the Diabetes Control and Complications Trial Research Group show that tight glycemic control early in pregnancy decreases the progression of a number of diabetic complications. However, it appears that the pre-existing tissue damage cannot be reversed even after normoglycemic levels are achieved during pregnancy. In recent years, considerable efforts have been made to investigate the etiology of birth defects among infants of diabetic mothers. It has been shown that diabetes-induced fetal abnormalities are accompanied by some metabolic disturbances including elevated superoxide dismutase (SOD) activity, reduced levels of myoinositol and arachidonic acid and inhibition of the pentose phosphate shunt pathway. Moreover, the frequency of fetal malformations in diabetic pregnancy has been reported to be markedly reduced by dietary supplements of antioxidants such as vitamin E, vitamin C and butylated hy- droxytoluene, suggesting that oxidative stress is involved in the etiology of fetal dysmorphogenesis. Furthermore, several experimental studies have shown that NTDs in embryos of diabetic mice are associated with altered expression of genes, which control development of the neural tube. In this review, recent findings of possible molecular mechanisms which cause morphological changes during neural tube development in embryos of diabetic pregnancy are discussed.

Resveratrol Prevents Impairment in Activation of Retinoic Acid Receptors and MAP Kinases in the Embryos of a Rodent Model of Diabetic Embryopathy

“…8 Data also indicate that preexisting tissue damage and aberrant cell specialization due to hyperglycemia cannot be reversed even after normoglycemic levels are achieved during pregnancy. 9 Furthermore, exposure of the fetus to maternal hyperglycemia may have long-term impact on fetal cellular programming and therefore result in a greater predisposition to different diseases. 10 Epidemiologic evidence indicates that mothers with diabetes mellitus during pregnancy increase the risk of their offspring developing schizophrenia in adulthood.…”

Cognitive Function in Offspring of Mothers with Gestational Diabetes–The Role of Insulin receptor

“…To elucidate the negative impacts of gestational diabetes on cognitive functioning in the children, several researchers have been reported that diabetic mothers had offspring with significantly lower mean IQs than control infants [1][2][3][4][10][11][12][13]. Moreover, many of the developmental effects of gestational diabetes on the fetal CNS can be attributed to maternal hyperglycemia and fetal hyperglycemia/hyperinsulinemia [5,38,39].…”

“…abnormalities in offspring [1][2][3][4][5]. Several lines of studies have reported the wide spectrum of effects of gestational diabetes on the central nervous system (CNS) development and function including neurocognitive and neurodevelopmental defects [1][2][3][4][6][7][8][9].…”

“…Several lines of studies have reported the wide spectrum of effects of gestational diabetes on the central nervous system (CNS) development and function including neurocognitive and neurodevelopmental defects [1][2][3][4][6][7][8][9]. Overall, it appears that these offspring have an increased risk for lower general IQ, inattention and hyperactivity and a poorer cognitive function [1][2][3][4][10][11][12][13]. Earlier investigations demonstrated a significant correlation between diabetes during pregnancy and lower IQ in offspring [10][11][12][13].…”

Use of folic acid during pregravid preparation and pregnancy

“…В од-ном из многочисленных исследований показано, что ком-плекс витаминов группы В (фолиевая кислота, витамины В 1 , В 2 , В 6 и В 12 ), витамин Е и минералы (кальций, железо, магний и цинк) редуцировали риск врожденной диафраг-мальной грыжи [64]. Употребление витаминов-антиокси-дантов (витамины С и Е) способствовало снижению ча-стоты ДНТ у детей женщин, больных сахарным диабетом [65]. В исследовании случай-контроль прием витамин-но-минеральных комплексов беременными женщинами полностью нивелировал риск развития тетрады Фалло и диспозиции крупных сосудов у детей [66].…”