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Updated: Jan 19, 2026
In Vivo Targeting of Neural Progenitor Cells in Ferret Neocortex by In Utero Electroporation
Published on: May 6, 2020
In utero exposure to maternal diabetes impairs nephron progenitor differentiation
Débora M Cerqueira1,2, Shelby L Hemker1,2, Andrew J Bodnar1,2
1Division of Nephrology, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Insights
Maternal diabetes during pregnancy reduces offspring
Area of Science:
- Developmental Biology
- Nephrology
- Endocrinology
Background:
- Diabetes mellitus incidence is rising in women of childbearing age.
- Prenatal exposure to maternal diabetes elevates congenital kidney anomaly risks in offspring.
- Congenital kidney anomalies are a primary cause of pediatric chronic kidney disease.
Purpose of the Study:
- To investigate the impact of maternal diabetes on kidney development in offspring.
- To analyze molecular and cellular changes in the kidneys of offspring exposed to maternal diabetes.
- To elucidate the mechanisms by which maternal diabetes affects nephrogenesis.
Main Methods:
- Utilized a mouse model (Akita mice) with diabetic mothers to study wild-type offspring (DM_Exp).
- Quantified total nephron number at postnatal day 34 using the physical dissector/fractionator method.
- Analyzed gene expression of nephron progenitor markers (SIX2, CITED1) and signaling pathway components (Notch1, LEF1) at postnatal day 2.
Main Results:
- DM_Exp mice exhibited a ~20% reduction in total nephron number compared to controls.
- Increased expression of nephron progenitor markers (SIX2, CITED1) was observed in DM_Exp kidneys.
- Diminished numbers of early developing nephrons were found in DM_Exp kidneys, linked to reduced Notch1 and Wnt/β-catenin signaling.
Conclusions:
- The diabetic intrauterine environment impairs nephron progenitor differentiation.
- Perturbation of Notch and Wnt/β-catenin signaling pathways may underlie developmental defects.
- Maternal diabetes adversely affects fetal kidney development, potentially increasing long-term kidney disease risk.
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 among the leading causes of chronic kidney disease in children. To better understand the effect of maternal diabetes on kidney development, we analyzed wild-type offspring (DM_Exp) of diabetic Ins2+/C96Y mice (Akita mice). DM_Exp mice at postnatal day 34 have a reduction of ~20% in the total nephron number compared with controls, using the gold standard physical dissector/fractionator method. At the molecular level, the expression of the nephron progenitor markers sine oculis homeobox homolog 2 and Cited1 was increased in DM_Exp kidneys at postnatal day 2. 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 and the canonical Wnt target lymphoid enhancer binding factor 1. Together, these data suggest that the diabetic intrauterine environment impairs the differentiation of nephron progenitors into nephrons, possibly by perturbing the Notch and Wnt/β-catenin signaling pathways.
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