Hyperglycemia: its imminent effects on mammalian nephrogenesis.
A sustained exposure of the mammalian embryo to very high glucose ambience is associated with a multitude of congenital birth defects, including those of the cardiovascular, CNS, skeletal and urogenital systems during the first 6-8 weeks of gestation in humans. These urogenital abnormalities may be associated with "caudal regression syndrome" or may occur alone in the form of partial or total renal agenesis. Similarly, an increase in the incidence of morphogenetic defects is observed in the offspring of streptozotocin-induced diabetic rats and mice, and also in non-obese diabetic mice. In certain cases, failure during the growth of the lower parts of embryos or newborn mice involving the genitourinary system has been observed in animals with severe diabetes. Investigators have utilized whole organ culture systems to delineate the mechanisms relevant to dysmorphogenesis of the embryonic metanephros. A marked dysmorphogenesis of the metanephros is observed upon treatment with a high concentration of D: -glucose. Associated with it are changes that include branching dysmorphogenesis of the ureteric bud iterations, reduced population of nascent nephrons, decreased expression of basement membrane proteoglycans, depletion of ATP stores, and fulminant apoptosis of the cells at the interface of mesenchyme and ureteric bud epithelium. The latter findings suggest that disruption of epithelial:mesenchymal interactions may be the major event responsible for the metanephric dysmorphogenesis induced by high glucose ambience.
Kanwar
Yashpal S
YS
Department of Pathology, Northwestern University Medical School, Chicago, IL, USA. y-kanwar@northwestern.edu
Nayak
Baibaswata
B
Lin
Sun
S
Akagi
Shigeru
S
Xie
Ping
P
Wada
Jun
J
Chugh
Sumant S
SS
Danesh
Farhad R
FR
D000818:Animals; D048909:Diabetes Complications; D047108:Embryonic Development; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007668:Kidney / Q000196:embryology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D011254:Pregnancy in Diabetics / Q000503:physiopathology