Folic Acid Supplementation Diminishes Diabetes- and Glucose-Induced Dysmorphogenesis in Rat Embryos In Vivo and In Vitro

Wentzel, Parri; Gäreskog, Mattias; Eriksson, Ulf J.

doi:10.2337/diabetes.54.2.546

Cited by 75 publications

(67 citation statements)

References 38 publications

(31 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since gene expression patterns dramatically change as development proceeds, subtle [7,12]. Thus, if the alteration in gene expression reflects the severity of influence of maternal hyperglycemia, severely affected fetus is expected to show larger alteration in gene expression.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Identification of Genes Differentially Expressed in Mouse Fetuses from Streptozotocin-induced Diabetic Pregnancy by cDNA Subtraction

et al. 2008

View full text Add to dashboard Cite

Abstract. Epidemiological studies have shown that the risks of fetal malformation such as neural tube defects increase in diabetic pregnancy. To explore the mechanism of fetal malformation induced by diabetes, cDNA subtraction using mouse embryos (E9.5) of diabetic dams and those of controls was performed to identify differentially expressed genes. The expression level of genes identified by cDNA subtraction was further verified by quantitative RT-PCR using E8.5 embryos, and differential expression of 4 genes, Brcc3, Commd3, Ddx1, and SET was confirmed. We also analyzed the expression level of neural tube defect-related genes, and found that Folbp1, EphrinA5 and Sox10 were differentially expressed. Altered expression of these genes mostly persisted throughout the later stages of the development (E10.5-14.5). Hierarchical clustering analysis showed correlation between expression levels of these genes, suggesting that these genes cooperatively play a role in embryonic development. Our results suggest that an altered gene expression profile in embryos underlies the development of congenital malformation in diabetic pregnancies.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Thus, discordant expression of various genes may also result in NTDs by diabetes. However, only limited number of genes, such as Pax3 [7,11] and folate binding protein 1 (Folbp1) [12], has been analyzed in these models.…”

mentioning

confidence: 99%

Identification of Genes Differentially Expressed in Mouse Fetuses from Streptozotocin-induced Diabetic Pregnancy by cDNA Subtraction

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Wentzel et al and our group [21,22] reported that mRNA expression of folic acid-binding protein (Folbp), a folic acid transporter, decreased in a diabetic state. It is thus suggested decreased Folbp level creates intrac-ellular folic acid deficiency in the embryo of diabetic pregnancy.…”

mentioning

confidence: 99%

Folic Acid Prevents Congenital Malformations in the Offspring of Diabetic Mice

et al. 2009

View full text Add to dashboard Cite

Abstract. It is well known that maternal diabetes causes various congenital malformations. Although there are many reports that folic acid (FA) administration in pregnancy reduces the risk of birth defects including neural tube defects (NTDs), a precise analysis on the preventive effect of FA against diabetic embryopathy has not been done yet. In this study, we analyzed the preventive effects of FA on congenital malformations including NTDs, cardiovascular, and skeletal malformations using a diabetic mouse model. Female mice were rendered hyperglycemic by streptozotocin and then mated. Pregnant diabetic mice were treated daily with FA (3 mg/kg body weight) or saline between gestational days (GD) 6 and 10. On GD 18, fetuses were examined for congenital malformations. FA did not affect plasma glucose levels. In the DM control group, the incidence of NTDs, cardiovascular, and skeletal malformations was 28.4%, 28.5%, and 29.7%, respectively. In the FA-treated group, the corresponding proportions reduced to 6.0%, 2.5% and 12.5%, respectively. A whole-mount TUNEL revealed an increased apoptosis in the hindbrain region of embryos from DM control group on day 9.5, and the apoptosis was decreased by FA treatment. Maternal plasma homocysteine levels on GD 9.5 were significantly lowered in DM control group compared with those in non-DM group, and FA treatment did not show a significant effect. These results indicate that FA is effective for the prevention of various diabetic embryopathy including NTDs, cardiovascular, and skeletal malformations, and suggested that this effect is independent from homocysteine metabolism and possibly mediated by decreasing the abnormal apoptosis during organogenesis.

show abstract

“…Study on pregnant mice fed with diets low in choline/methionine have resulted in decreased methylation in genes that control brain development [47,48] , and altered memory and long-term potentiation [49,50] indicating that the developing embryo is influenced by maternal diet. In addition, diabetic rodents supplemented with folate (a methyl donor) prevented NTDs in the embryos [51,52] that define the role of maternal nutrition on fetal outcome.…”

Section: Unravelling Epigenetic Mechanisms Contributing To Ntdsmentioning

confidence: 99%

Frontiers in research on maternal diabetes-induced neural tube defects: Past, present and future

Sudhaharan

Bay²,

Tay³

et al. 2012

WJD

View full text Add to dashboard Cite

Diabetes mellitus rightly regarded as a silent-epidemic is continually on the rise and estimated to have a global prevalence of 6.4 % as of 2010. Diabetes during pregnancy is a well known risk factor for congenital anomalies in various organ systems that contribute to neonatal mortality, including cardiovascular, gastrointestinal, genitourinary and neurological systems, among which the neural tube defects are frequently reported. Over the last two to three decades, several groups around the world have focussed on identifying the molecular cues and cellular changes resulting in altered gene expression and the morphological defects and in diabetic pregnancy. In recent years, the focus has gradually shifted to looking at pre-programmed changes and activation of epigenetic mechanisms that cause altered gene expression. While several theories such as oxidative stress, hypoxia, and apoptosis triggered due to hyperglycemic conditions have been proposed and proven for being the cause for these defects, the exact mechanism or the link between how high glucose can alter gene expression/transcriptome and activate epigenetic mechanisms is largely unknown. Although preconceptual control of diabetes, (i.e., managing glucose levels during pregnancy), and in utero therapies has been proposed as an effective solution for managing diabetes during pregnancy, the impact that a fluctuating glycemic index can have on foetal development has not been evaluated in detail. A tight glycemic control started before pregnancy has shown to reduce the incidence of congenital abnormalities in diabetic mothers. On the other hand, a tight glycemic control after organogenesis and embryogenesis have begun may prove insufficient to prevent or reverse the onset of congenital defects. The importance of determining the extent to which glycemic levels in diabetic mothers should be regulated is critical as foetal hypoglycemia has also been shown to be teratogenic. Finally, the major question remaining is if this whole issue is negligible and not worthy of investigation as the efficient management of diabetes during pregnancy is well in place in many countries.

show abstract

Folic Acid Supplementation Diminishes Diabetes- and Glucose-Induced Dysmorphogenesis in Rat Embryos In Vivo and In Vitro

Cited by 75 publications

References 38 publications

Identification of Genes Differentially Expressed in Mouse Fetuses from Streptozotocin-induced Diabetic Pregnancy by cDNA Subtraction

Identification of Genes Differentially Expressed in Mouse Fetuses from Streptozotocin-induced Diabetic Pregnancy by cDNA Subtraction

Folic Acid Prevents Congenital Malformations in the Offspring of Diabetic Mice

Frontiers in research on maternal diabetes-induced neural tube defects: Past, present and future

Contact Info

Product

Resources

About