In utero exposure to maternal diabetes impairs nephron progenitor
Authors Cerqueira DM, Hemker SL, Bodnar AJ, Ortiz DM, Oladipupo FO, Mukherjee E, Gong Z,
Appolonia C, Muzumdar RH, Sims-Lucas S, Ho J
Submitted By Sunder Sims-Lucas on 10/14/2019
Status Published
Journal American journal of physiology. Renal physiology
Year 2019
Date Published 9/1/2019
Volume : Pages Not Specified : Not Specified
PubMed Reference 31509011
Abstract The incidence of diabetes mellitus has significantly increased among women of
childbearing age and it has been shown that prenatal exposure to maternal
diabetes increases the risk of associated congenital anomalies of the kidney.
Congenital anomalies of the kidney are amongst the leading causes of chronic
kidney disease in children. To better understand the effect of maternal diabetes
on kidney development, we analyzed wildtype offspring (DM_Exp) of diabetic
Ins2+/C96Ymice (Akitamice). DM_Exp mice at postnatal day 34 (P34) have a
reduction of approximately 20% in the total nephron number compared to controls,
using the gold-standard physical dissector/fractionator method. At the molecular
level, the expression of the nephron progenitor markers Six2 and Cited1was
increased in DM_Exp kidneys at postnatal day 2 (P2). Conversely, the number of
early developing nephrons was diminished in DM_Exp kidneys. This was associated
with decreased expression of the intracellular domain of Notch1 (NICD1) and the
canonical Wnt target lymphoid enhancer binding factor 1 (Lef1). Together, these
data suggest that the diabetic intrauterine environmentimpairs the
differentiation of nephron progenitors into nephrons, possibly by perturbing the
Notch and Wnt/b-catenin signaling pathways.