Myo-inositol and prostaglandins reverse the glucose inhibition of neural tube fusion in cultured mouse embryos

Baker, Lester; Piddington, Ronald; Goldman, Alvin I.; Egler, Joseph; Moehring, Joan M.

doi:10.1007/bf00400202

Cited by 110 publications

(89 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The major products of lipid peroxidation, the hydroperoxides, are known stimulants of prostaglandin biosynthesis but inhibit the production of prostacyclin [54], an imbalance which may have deleterious effects on the embryo. The previous findings of a beneficial effect of arachidonic acid [33,34], prostaglandin E~ and F2c~ and prostacyclin [39] on embryos in a diabetic environment may also relate to this notion, since the supplementation of these substances may correct a possible imbalance in prostaglandin biosynthesis. Likewise, the finding of a beneficial effect of myo-inositol supplementation to high-glucose culture [39,40], compensating for a decreased embryonic uptake of this hexose [41], may be explained by a restored production of phosphatidylinositol and a subsequent normalization of phospholipase A2 activity [55].…”

Section: Discussionmentioning

confidence: 90%

“…Thus, both a high concentration of glucose [9], a low glucose concentration [31] and a high concentration of [3-hydroxybutyrate [32] have been shown to be teratogenic in vitro. Furthermore, various consequences of increased ambient glucose concentration have been suggested to play a role in the disturbed embryogenesis, such as arachidonic acid depletion [33,34], hyperaccumulation of sorbitol [35][36][37][38], deficiency of myo-inositol [36,37,[39][40][41] or alterations in trace metal concentrations of the offspring [42,43]. Mannose [44,45] and somatomedin inhibitors from serum of diabetic rats [46] also cause embryonic malformations.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Protection by free oxygen radical scavenging enzymes against glucose-induced embryonic malformations in vitro

1991

View full text Add to dashboard Cite

Summary. This study addresses the possibility that the teratogenic effects of a diabetic pregnancy are associated with increased embryonic activities of free oxygen radicals. Rat embryos were cultured in 50 mmol/1 glucose for 48h and subsequently showed pronounced growth retardation and severe malformations. The enzyme inducer citiolone and the free oxygen radical scavenging enzymes superoxide dismutase, catalase and glutathione peroxidase protected against the disturbed growth and development of the embryos at 50 mmol/1 glucose when added to the culture media. Enzymatic measurements indicated that citiolone induced an increased activity of superoxide dismutase in the embryonic tissues and that the added enzymes were taken up by both the yolk sac and the embryo proper. The protection against embryonic maldevelopment was thus conferred by agents that increased the free oxygen radical scavenging capacity of the embryonic tissues. The results suggest that a high glucose concentration in vitro causes embryonic dysmorphogenesis by generation of free oxygen radicals. An enhanced production of such radicals in embryonic tissues may be directly related to the increased risk of congenital malformations in diabetic pregnancy.

show abstract

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Protection by free oxygen radical scavenging enzymes against glucose-induced embryonic malformations in vitro

1991

View full text Add to dashboard Cite

show abstract

“…Preventive strategies have been examined in laboratory animals based on knowledge of these pathways, in attempts to reduce diabetic embryopathy associated with high glucose levels. For example, birth defect incidence has been reduced in diabetic mice by dietary supplementation with myoinositol (Baker et al, 1990), arachidonic acid (Goldman et al, 1985;Pinter et al, 1986), lipoic acid (Wiznitzer et al, 1999), or antioxidants including vitamin E (Sivan et al, 1996) and vitamin C (Siman and Eriksson, 1997). Torchinsky et al (1997) stimulated uterine immune cells in pregnant mice in an attempt to reduce fetal resorptions associated with diabetes, and made the unexpected observation of significantly reduced malformed fetuses.…”

Section: Maxillary Lengthmentioning

confidence: 99%

Reduction in diabetes‐induced craniofacial defects by maternal immune stimulation

Hrubec

Prater

Toops

et al. 2005

Birth Defects Research Pt B

View full text Add to dashboard Cite

BACKGROUND: Maternal diabetes can induce a number of developmental abnormalities in laboratory animals and humans, including facial deformities and defects in neural tube closure. The incidence of birth defects in newborns of diabetic women is approximately 3–5 times higher than among non‐diabetics. In mice, non‐specific activation of the maternal immune system can reduce fetal abnormalities caused by diverse etiologies, including diabetes induced neural tube defects. This study was conducted to determine whether non‐specific maternal immune stimulation could reduce diabetes‐induced craniofacial defects as well. METHODS: Maternal immune function was stimulated before streptozocin (STZ) treatment by maternal footpad injection with Freund's complete adjuvant (FCA), maternal intraperitoneal (i.p.) injection with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), or maternal i.p. injection with interferon‐γ (IFNγ). Streptozocin (200 mg/kg i.p.) was used to induce hyperglycemia (26–35 mmol blood glucose) in female ICR mice before breeding. Fetuses from 12–18 litters per treatment group, were collected at Day 17 of gestation. RESULTS: Craniofacial defects were observed in fetuses from all hyperglycemic groups. The incidence of defects was significantly decreased in fetuses from dams immune stimulated with IFNγ or GM‐CSF. The most common defects were reduced maxillary and mandibular lengths. Both were prevented by maternal stimulation with GM‐CSF. CONCLUSION: Maternal immune stimulation reduced the incidence of diabetic craniofacial embryopathy. The mechanisms for these protective effects are unknown but may involve maternal or fetal production of cytokines or growth factors that protect the fetus from the dysregulatory effects of hyperglycemia. Birth Defects Res Part B 2006. © 2005 Wiley‐Liss, Inc.

show abstract

“…Maternal diabetes in rats and mice has shown impaired embryonic growth at the pre-implantation stage [12] While other diabetesrelated factors such as triglycerides and branched amino acid chains may influence the outcome of pregnancy [13], it has been suggested that the primary teratogen in diabetic pregnancy is hyperglycemia [14][15][16][17]. A number of teratological pathways in embryonic tissue have been identified, including variations in metabolism of inositol, arachidonic acid and reactive oxygen species (ROS) [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Oxidant release is dramatically increased by elevated glucose concentrations in neutrophils from pregnant women

Petty

Kindzelskii

Chaiworapongsa

et al. 2005

The Journal of Maternal-Fetal & Neonatal Medicine

View full text Add to dashboard Cite

Objective. To evaluate the mechanism of oxidative stress at glucose levels accompanying diabetic pregnancy. Specifically, we hypothesize that elevated glucose overwhelms hexose monophosphate shunt (HMS) down-regulation observed during pregnancy. Methods. Peripheral blood cells from normal healthy pregnant women were exposed to heightened glucose levels to provide an in vitro model of the effects of diabetic pregnancy. Changes in NAD(P)H, reactive oxygen species (ROS) and nitric oxide (NO) production were evaluated in single cells. Results. Altered metabolic dynamics, as judged by NAD(P)H autofluorescence of neutrophils from both pregnant and nonpregnant women, were observed during incubation with 14 mM glucose, a pathophysiologic level. In parallel, increased production of ROS and NO was observed. The ROS and NO levels attained in cells from pregnant women were greater than those observed in cells from non-pregnant women. Inhibitors of the HMS and NAD(P)H oxidase blocked these effects. These metabolic and oxidant changes required approximately one minute, suggesting that transient glucose spikes during pregnancy could trigger this response. Conclusions. Elevated glucose levels enhance HMS activity and oxidant production in cells from pregnant women. This mechanism may be generally applicable in understanding the role of diabetes in materno-fetal health.

show abstract

Myo-inositol and prostaglandins reverse the glucose inhibition of neural tube fusion in cultured mouse embryos

Cited by 110 publications

References 36 publications

Protection by free oxygen radical scavenging enzymes against glucose-induced embryonic malformations in vitro

Protection by free oxygen radical scavenging enzymes against glucose-induced embryonic malformations in vitro

Reduction in diabetes‐induced craniofacial defects by maternal immune stimulation

Oxidant release is dramatically increased by elevated glucose concentrations in neutrophils from pregnant women

Contact Info

Product

Resources

About