Teratogenic effects of excess glucose on head‐fold rat embryos in culture

Cockroft, D. L.; Coppola, Paola

doi:10.1002/tera.1420160205

Cited by 192 publications

(95 citation statements)

References 16 publications

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“…These studies have confirmed that severe malformations can be caused merely by increasing the glucose concentration of the culture medium [68,69]. The chick egg is also malformation-sensitive to glucose and several other sugars during early incubation [70].…”

Section: Fetal Abnormalitiesmentioning

confidence: 79%

Diabetes in pregnancy 1985

Hadden

1986

Diabetologia

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The art of obstetrics is not a subject which is often discussed in the pages of Diabetologia. However, as the care of the diabetic mother and her offspring is rightly an interdisciplinary responsibility between obstetrician, diabetologist and neonatologist, it is important that each has a close understanding of the various problems. Dr. M. I. Drury (Dublin), speaking as an internist, raises a question on the optimum time and method of delivery of the baby; this has more than purely obstetrical implications. Drs. L. Molsted-Pedersen (Copenhagen) and C. K~ihl (Copenhagen and Klampenborg), obstetrician and internist from the longest-established joint obstetric/diabetic service in the world, present a Scandinavian view on the management of pregnancy. Both centres have distinguished records in the management of diabetic pregnancy. The different viewpoints in Denmark and in Ireland are clear -in Copenhagen, therapeutic abortion is practiced in a pregnancy at risk of severe congenital malformation; in Dublin it is not. Dr. Drury quotes a perinatal loss of 13 of 285 pregnancies (4.5%) in the past 5 years, but does not include the recognised spontaneous abortions which, on his overall figures, are about 10% of conceptions. Dr. Molsted-Pedersen reports a perinatal loss of 3 of 201 infants (1.5%), excluding 17 spontaneous and 9 induced abortions. If these 9 aborted pregnancies, which were performed due to a risk of severe congenital malformation, were included as fatalities, the Copenhagen figure would be 12 of 210 (5.5%). Of course, we do not know if all those 9 fetuses were affected. The spontaneous abortion rate was 17 of 223 (8.0%). Thus, if total fetal loss is taken as the index, there appears to be little difference between the two centres. The clinical controversy on the timing and method of birth in the different centres will continue --pundits can be conservative as well as radical, and, as Dr. Drury remarks, the truth probably lies somewhere in between.The bottom line in reports on the management of diabetes in pregnancy used to be the perinatal mortality (from 28 weeks gestation to the end of the first week of life). With the continuing improvement in neonatal care, more babies who would have died during the perinatal period are surviving beyond the seventh day of life. As a result, their subsequent deaths are not recorded in many publications. Even greater emphasis will fall on the quality of life for those infants surviving with a major congenital abnormality (heart and neural tube defect) which produces profound childhood morbidity. Prevention of these congenital abnormalities is the most important aim of pre-and early conceptional care of the diabetic mother. Both centres which report their recent results in this issue would agree that there has been an improvement even in the past 5 years -the problem is to define exactly which developments account for the change for the better, and which previously-trusted techniques can safely be allowed to fall by the wayside.

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Section: Fetal Abnormalitiesmentioning

confidence: 79%

Diabetes in pregnancy 1985

Hadden

1986

Diabetologia

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“…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].…”

Section: Discussionmentioning

confidence: 99%

“…they were cultured in a high glucose concentration known to cause growth retardation and malformations [9][10][11]. The culture media were supplemented either with citiolone (N-acetyl-DL-homocysteine thiolactone), which is an inducer of oxygen radical scavenging enzymes [12,13], or with superoxide dismutase, catalase or glutathione peroxidase.…”

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confidence: 99%

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

1991

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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.

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“…Environmental insults during this developmental window lead to defects in the cardiovascular system, which subsequently affect the development of several embryonic organs. An in vitro whole embryo culture model permits study of this crucial developmental period and has shown that short exposure to hyperglycemia is teratogenic, causing dose dependent growth retardation, neural tube lesions and yolk sac failure (Cockroft and Coppola, 1977;Pinter et al, 1999;Reece et al, 1996;Rashbass and Ellington, 1988;Sadler, 1980a;Sadler, 1980b;Freinkel et al, 1986). Additionally, this model system mimics the morphological and biochemical vascular defects in the embryo and yolk sac observed in vivo (New et al, 1976;Mills et al, 1979;Sadler and Warner, 1984).…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide modulates murine yolk sac vasculogenesis and rescues glucose induced vasculopathy

et al. 2004

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Nitric oxide (NO) has been demonstrated to mediate events during ovulation,pregnancy, blastocyst invasion and preimplantation embryogenesis. However,less is known about the role of NO during postimplantation development. Therefore, in this study, we explored the effects of NO during vascular development of the murine yolk sac, which begins shortly after implantation. Establishment of the vitelline circulation is crucial for normal embryonic growth and development. Moreover, functional inactivation of the endodermal layer of the yolk sac by environmental insults or genetic manipulations during this period leads to embryonic defects/lethality, as this structure is vital for transport, metabolism and induction of vascular development. In this study, we describe the temporally/spatially regulated distribution of nitric oxide synthase (NOS) isoforms during the three stages of yolk sac vascular development (blood island formation, primary capillary plexus formation and vessel maturation/remodeling) and found NOS expression patterns were diametrically opposed. To pharmacologically manipulate vascular development,an established in vitro system of whole murine embryo culture was employed. During blood island formation, the endoderm produced NO and inhibition of NO(L-NMMA) at this stage resulted in developmental arrest at the primary plexus stage and vasculopathy. Furthermore, administration of a NO donor did not cause abnormal vascular development; however, exogenous NO correlated with increased eNOS and decreased iNOS protein levels. Additionally, a known environmental insult (high glucose) that produces reactive oxygen species(ROS) and induces vasculopathy also altered eNOS/iNOS distribution and induced NO production during yolk sac vascular development. However, administration of a NO donor rescued the high glucose induced vasculopathy, restored the eNOS/iNOS distribution and decreased ROS production. These data suggest that NO acts as an endoderm-derived factor that modulates normal yolk sac vascular development, and decreased NO bioavailability and NO-mediated sequela may underlie high glucose induced vasculopathy.

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Teratogenic effects of excess glucose on head‐fold rat embryos in culture

Cited by 192 publications

References 16 publications

Diabetes in pregnancy 1985

Diabetes in pregnancy 1985

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

Nitric oxide modulates murine yolk sac vasculogenesis and rescues glucose induced vasculopathy

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