Placental Growth and Glycogen Metabolism in Streptozotocin Diabetic Rats

Gewolb, Ira H; Barrett, Cynthia T.; Warshaw, Joseph B.

doi:10.1203/00006450-198307000-00014

Cited by 33 publications

(13 citation statements)

References 30 publications

(37 reference statements)

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“…The differences in protein and DNA concentrations between (db/+) and control fetal mice varied from organ to organ. Gewolb et al found placental hypertrophy (in spite of small fetal body wt) in fetuses of the streptozotocin rat, and interpreted changes in protein and DNA concentrations as evidence of abnormally prolonged placental growth in late gestation (23). The (db/+) placentas in this study showed a decreased concentration of DNA (i.e.…”

Section: Discussionmentioning

confidence: 60%

“…The fetal mouse or rat begins to mobilize lung, liver, and placental glycogen 1 to 2 days before birth (18,(22)(23)(24). Gewolb and coworkers (18,23) found that this normal glycogen breakdown was delayed in fetuses of the streptozotocin rat model due to altered activity of enzymes in the gluconeogenesis and glycogenolysis pathways. Similarly, the liver of the (db/+) fetal mouse accumulated abnormally increased amounts of glycogen, and glycogen breakdown in the placenta was delayed.…”

Section: Discussionmentioning

confidence: 99%

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Delayed Lung Maturation in the Macrosomic Offspring of Genetically Determined Diabetic (db/+) Mice1

1989

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ABSTRACT. We studied a genetically determined diabetes in pregnancy, the heterozygous diabetes (db/+) mouse. We found that fetal mice from these pregnancies are macrosomic with increased body, lung, and placenta wt, have altered organ protein, DNA and phospholipid content, and exhibit abnormal carbohydrate metabolism with increased liver and glycogen content. We further studied the effect of increased substrate availability and utilization on lung growth and maturation in (db/+) fetal mice, by measuring lung phospholipid synthesis as represented by the incorporation of the radiolabeled precursors, [3H] The increased synthesis of lung disaturated phosphatidylcholine in diabetic fetal mice may reflect the enhancement of body and lung growth in these macrosomic fetuses. Lung maturation, as represented by phosphatidylglycerol synthesis, the phosphatidylglycerol/phosphatidylinositol ratio, and morphologic indices, was abnormal in diabetic fetuses. The diabetic mouse is a useful model for studying the mechanisms resulting in enhanced growth and concomitant alterations in lung maturation in the infant of a diabetic mother. (Pediatr Res 25:173-179, 1989) Abbreviations RDS, respiratory distress syndrome PC, phosphatidylcholine SPC, disaturated phosphatidylcholine S, sphingomyelin PI, phosphatidylinositol PE, phosphatidylethanolamine PS, phosphatidylserine PG, phosphatidylglycerol Human fetal development during maternal diabetes is abnormal, frequently resulting in obese, macrosomic newborns with delayed maturation of various organ systems. Infants of diabetic mothers whose hyperglycemia is inadequately controlled late in gestation appear to have an increased risk of lung immaturity, as manifested by RDS at birth (I). Animal models in which maternal glucose intolerance and consequent fetal hyperglycemia are artificially induced have been developed to study this phenomenon (2). However, important questions concerning maternal-fetal interactions in diabetes and the consequent effects on fetal organ growth and development might be more appropriately addressed by using a model in which the diabetes is genetically determined, therefore occuning spontaneously in the mother (2).The diabetic mouse (db/db) is a well-described model of genetic diabetes transferred as an autosomal recessive trait. Homozygous (db/db) animals exhibit visible obesity in infancy with marked hyperglycemia and insulin resistance, followed later by hypoinsulinemia and profound diabetes at 3-4 mo of age (3). As the adult (db/db) mouse is infertile, heterozygous animals must be bred to produce offspring. The heterozygous female (db/ +) exhibits normal glucose tolerance except during pregnancy, when abnormal glucose tolerance, postprandial hyperglycemia and elevated Hb A 1C levels are present (4,5).We have studied the fetus of the pregnant heterozygous (db/ +) female to learn more about growth and the development during pregnancy complicated by abnormal glucose metabolism. In this report, we describe our results in characterizing abnormal fetal growth duri...

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Delayed Lung Maturation in the Macrosomic Offspring of Genetically Determined Diabetic (db/+) Mice1

1989

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“…In these studies, the diabetic placenta at term was characterized by a placentomegaly, large numbers of glycogen-distended cells in the basal zone and degeneration of the trophoblast cells in the labyrinth zone. DNA synthesis continued for an additional 2 to 3 days after the control placenta had completed DNA synthesis, but placental content of DNA did not differ between diabetic placentas and healthy control placentas when the DNA content was normalized to placental weight [30,31,32,33].…”

Section: Discussionmentioning

confidence: 99%

Effect of high concentrations of glucose on differentiation of rat trophoblast cells in vitro

et al. 2003

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Aims/hypothesis. Previous studies have shown that diabetic placentas are characterized by structural and biochemical anomalies, including defects in the differentiation of trophoblasts. In this study, the Rcho-1 cell line was used to investigate the impact of high glucose concentrations on different markers of differentiation of rat trophoblast cells in giant cells (endoreduplication, invasive phenotype and endocrine phenotype). Materials. Rcho-1 cells were incubated for 12 days in medium supplemented with different concentrations of glucose and 10% horse serum to optimize differentiation. The cells were examined for the proportion of nuclei showing signs of apoptosis. The effect of high glucose was investigated on the endoreduplication process, on invasive phenotype (secretion of gelatinase B) and on endocrine phenotype (expression of placental lactogen I (PL-I) and II (PL-II) and progesterone secretion). Results. Apoptosis was not induced by high glucose in Rcho-1. The number of cells was higher in the cultures exposed to high glucose (p<0.05) and their nuclei contained more DNA compared with control cells (p<0.001), while their nuclear size was smaller (p<0.001). Gelatinase B secretion increased during differentiation but no difference was found when gelatinase B secretion from trophoblasts exposed to high glucose was compared with the control cells. Rcho-1 cell cultures showed an increase in PL-I and PL-II mRNA expressions during differentiation and which was not affected by high glucose. Progesterone secretion increased during differentiation in control cultures. However, this increase was abolished when trophoblasts were cultured in high glucose. Conclusions/interpretation. Our data suggest that high glucose influences the endoreduplication process and the steroidogenesis during differentiation of rat trophoblasts. [Diabetologia (2003) 46:276-283]

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“…Placentas from diabetic animals at term (22 d) were histologically similar to 18-d control placentas. The amount of DNA in these placentas increases until the 19th day ofgestation whereas maximum levels ofDNA occur by days 16-17 in placentas from control rats (4). It can be speculated that the decrease in EGF binding in the diabetic placenta is related to continued cell proliferation rather than maturation.…”

Section: Discussionmentioning

confidence: 96%

“…Infants of diabetic mothers also exhibit a delay in lung maturation and a greatly increased risk for the development of hyaline membrane disease (3). In previous studies utilizing fetuses of streptozotocin-diabetic rats (4,5), we reported that hyperglycemia per se was associated with increased placental growth and delayed maturation during late gestation. DNA levels reach a maximum on day 16 in placentas from control rats whereas placentas from diabetic rats continue to increase in DNA content until days [18][19] and are morphologically immature when compared with control tissues.…”

Section: Introductionmentioning

confidence: 99%

Decreased binding of epidermal growth factor in placentas from streptozotocin-diabetic rats.

Sissom¹,

Stenzel²,

Warshaw³

1987

J. Clin. Invest.

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Placentas from streptozotocin-diabetic rats have previously been shown to be morphologically and biochemically immature when compared with those of control rats. The binding of epidermal growth factor (EGF) to plasma membranes prepared from placentas of control and streptozotocin-diabetic fetuses has been characterized on days 17 and 21 of gestation. Results from competitive binding data analyzed by Scatchard analysis indicate the presence of a single class of receptors on day 17 (KD = 5.4 X 10-10) and the appearance of a second class of binding sites for`zI-EGF by day 21 (KD= 3.5 X 10'9) in membranes from control fetuses. Placental membranes from diabetic fetuses show decreased specific binding (-30%) on both days and the absence of a second class of binding sites on day 21 of gestation. Results from a radioreceptor assay indicate that the quantity of EGF in the serum of fetuses removed from control rats on day 21 is twofold greater than the quantity in sermm offetuses from diabetic rats. These data reveal a developmental increase in EGF-binding sites in the placenta of normal near-term fetal rats, largely because of the appearance of a second class of binding sites with a lower affinity for WGF. The failure (or delay) of this second class to develop in the diabetic may be important for the control of maturation and growth of this tissue.

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Placental Growth and Glycogen Metabolism in Streptozotocin Diabetic Rats

Cited by 33 publications

References 30 publications

Delayed Lung Maturation in the Macrosomic Offspring of Genetically Determined Diabetic (db/+) Mice1

Delayed Lung Maturation in the Macrosomic Offspring of Genetically Determined Diabetic (db/+) Mice1

Effect of high concentrations of glucose on differentiation of rat trophoblast cells in vitro

Decreased binding of epidermal growth factor in placentas from streptozotocin-diabetic rats.

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