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

Abstract

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...

Altered contribution of RhoA/Rho kinase signaling in contractile activity of myometrium in leptin receptor-deficient mice

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miR-410 enhanced hESC-derived pancreatic endoderm transplant to alleviate gestational diabetes mellitus

“…Although sharing the usual suspect of diabetic symptoms, such as hyperglycemia, hyperinsulinemia, overweight, elevated fat content, liver and plasma TG, FFA and leptin levels, GDM is distinct from type 2 diabetes in that GDM also affects reproductive outcome and fetal development (Lawrence et al 1989, Ishizuka et al 1999, Yamashita et al 2001, Siemelink et al 2002, Buckley et al 2005. Results from our study were consistent with reports on the same db/C GDM mouse model, with w10% increase in body weight from litters born by GDM dam, whereas miR-PE transplated GDM females gave birth to litters with body weight comparable to those from WT dam.…”

“…Particularly in db/C GDM mouse model, fetus weight at term was reported to increase by 5-8% (Lawrence et al 1989, Yamashita et al 2001. This has prompted us to investigate whether our miR-PE transplant was able to improve fetal development of GDM female mice.…”

“…Prior to pregnancy, they exhibited largely normal glucose tolerance until late gestation (Ishizuka et al 1999, Lambin et al 2007. Fetal development was also defective with fetus weight at term increased by 5-8% (Lawrence et al 1989, Yamashita et al 2001. Advances in stem cell technology have provided exciting development in diabetes treatment in animal models.…”

Is Low-Dose streptozotocin in Rats an Adequate Model for Gestational Diabetes Mellitus?

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