The Honeybee Syndrome - Implications of the Teratogenicity of Mannose in Rat Embryo Culture

Freinkel, Norbert; Lewis, Nancy Jo; Akazawa, Shoichi; Roth, Steffen; Gorman, Lisa

doi:10.1097/00132582-198404030-00013

Cited by 20 publications

(37 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although efficient insulin treatment appears to reduce the rate of malformation [6,7], the nature of the diabetic aggression leading to teratogenesis is not known [5]. Recent developments draw attention to very early steps in embryo development, close to the implantation period, which might be more sensitive to metabolic disturbances [8][9][10]. The investigation of the embryo-maternal interrelationship around the time of implantation could be an important approach in the understanding of the deleterious effect a metabolically disturbed environment could exert on early embryo development, implantation and further differentiation.…”

Section: Discussionmentioning

confidence: 99%

Oestrogen and progestogen receptors in endometrium and myometrium at the time of blastocyst implantation in pregnant diabetic rats

Hertogh¹,

Vanderheyden²,

Glorieux³

et al. 1989

Diabetologia

View full text Add to dashboard Cite

Summary.A suitable hormonal environment is a prerequisite for blastocyst implantation. Experimental diabetes was previously shown to modify the hormonal milieu and produce alterations in oestrogen receptor kinetics in the uterine tissue. In the present work, oestrogen and progestogen receptor levels were measured on the morning of day 6 of pregnancy in normal and in streptozotocin-induced diabetic rats, both in implantation sites and in interembryonic segments of endometrium and myometrium. Receptor levels were different in the implantation sites compared to the interembryonic segments of endometrium, both in the control and in the diabetic animals. Indeed, implantation sites were characterized by lower oestrogen receptor levels in cytosol and higher progestogen receptor levels in cytosol and nuclei. However, compared to the control rats, the diabetic rats had lower oestrogen receptor levels in implantation sites, both in cytosol and nuclei. In the myometrium, the differences between sites or between types of rats were minimal. Plasma levels of oestradiol were lower in diabetic rats than in control animals, whereas progesterone levels were similar. A 20% lower implantation rate was found in diabetic rats, compared to normal rats. These results show that the specific distribution of oestrogen and progestogen receptors between implantation sites and interembryonic segments was preserved in the diabetic rats; however the absolute level of oestrogen receptor was lower. This abnormal endocrine milieu might arise from a lower oestradiol level and a decreased oestradiol/progesterone ratio in the circulating blood. Whether the lower implantation rate in diabetic rats might be a consequence of the overall disturbed hormonal status remains to be elucidated.

show abstract

Section: Discussionmentioning

confidence: 99%

Oestrogen and progestogen receptors in endometrium and myometrium at the time of blastocyst implantation in pregnant diabetic rats

Hertogh¹,

Vanderheyden²,

Glorieux³

et al. 1989

Diabetologia

View full text Add to dashboard Cite

show abstract

“…The congenital defects include failure in the closure of neural tube, caudal regression syndrome, and genito-urinary abnormalities, including agenesis of the kidney. Similarly, an increased incidence of congenital defects has been observed in the offsprings of alloxan-and streptozotocin-induced diabetic rats and mice (10)(11)(12)(13)(14), and also in nonobese diabetic mice (15). In embryos of these murine diabetic mothers, changes in some of the ECM macromolecules (16), altered mitochondrial morphology of the anterior neuropore (17), perturbed phosphorylation or dephosphorylation processes relevant to the tyrosine kinase activities of growth factor receptors (18,19), and metabolism of myo-inositol (20) have been described.…”

Section: Introductionmentioning

confidence: 92%

“…The induction of such embryonic defects and the mechanisms involved have been further investigated in whole rat embryo culture systems (22,23). Exposure of rat embryos, harvested during the midgestational period, to elevated concentrations of aldohexoses (i.e., glucose, fructose, mannose, and galactose) for 3-4 d results in the development of complex abnormalities confined to the lower half of the body; e.g., nonclosure of the neural tube (13,14,23). These extensive in vivo as well as in vitro studies, carried out over a period of 2-3 decades, strongly suggest a significant correlation between the hyperglycemic state and abnormal development of the mammalian embryo.…”

Section: Introductionmentioning

confidence: 99%

D-glucose-induced dysmorphogenesis of embryonic kidney.

Kanwar¹,

Liu²,

Kumar³

et al. 1996

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Insulin-induced hypoglycaemia may also produce malformations in the chick embryo, and this effect has been shown in early embryogenesis in the rabbit [62]. The lethal effects of Dmannose in the honeybee have been known for over 50 years, and Freinkel et al [71] have shown in culture of nine and a half day rat embryos that D-mannose will cause the growth retardation and faulty neural tube closure associated with inhibition of glycolysis. This model shows the metabolic vulnerability during early organogenesis and may explain the teratogenesis of other seemingly unrelated agents, such as trace element abberations, at the same stage.…”

Section: Fetal Abnormalitiesmentioning

confidence: 99%

Diabetes in pregnancy 1985

Hadden

1986

Diabetologia

View full text Add to dashboard Cite

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.

show abstract

The Honeybee Syndrome - Implications of the Teratogenicity of Mannose in Rat Embryo Culture

Cited by 20 publications

References 0 publications

Oestrogen and progestogen receptors in endometrium and myometrium at the time of blastocyst implantation in pregnant diabetic rats

Oestrogen and progestogen receptors in endometrium and myometrium at the time of blastocyst implantation in pregnant diabetic rats

D-glucose-induced dysmorphogenesis of embryonic kidney.

Diabetes in pregnancy 1985

Contact Info

Product

Resources

About