Altered Ureteric Branching Morphogenesis and Nephron Endowment in Offspring of Diabetic and Insulin-Treated Pregnancy

Hokke, Stacey; Armitage, James A.; Puelles, Victor G.; Short, Kieran M.; Jones, Lynelle K.; Smyth, Ian; Bertram, John F.; Cullen‐McEwen, Luise A.

doi:10.1371/journal.pone.0058243

Cited by 56 publications

(57 citation statements)

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“…Stereological methods have been used to determine the glomerular number in kidneys affected by pneumoperitoneum, diabetes, and chronic stress 19,22,26 . Stereological glomeruli quantification has also been used to study renal damage after partial nephrectomy 14 or for comparing arteriovenous with arterial renal ischemia 13 .…”

Section: ■ Discussionmentioning

confidence: 99%

The relationship between renal warm ischemia time and glomerular loss. An experimental study in a pig model

et al. 2017

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The relationship between renal warm ischemia time and glomerular loss. An experimental study in a pig model 1 Acta Cir. Bras. 2017;32(5):334-341 Abstract Purpose: To investigate the glomerular number after different warm ischemia times. Methods: Thirty two pigs were assigned into four groups. Three groups (G10, G20, and G30) were treated with 10, 20, and 30 minutes of left renal warm ischemia. The sham group underwent the same surgery without renal ischemia. The animals were euthanized after 3 weeks, and the kidneys were collected. Right kidneys were used as controls. The kidney weight, volume, cortical-medullar ratio, glomerular volumetric density, volume-weighted mean glomerular volume, and the total number of glomeruli per kidney were obtained. Serum creatinine levels were assessed pre and postoperatively. Results: Serum creatinine levels did not differ among the groups. All parameters were similar for the sham, G10, and G20 groups upon comparison of the right and left organs. The G30 group pigs' left kidneys had lower weight, volume, and cortical-medullar ratio and 24.6% less glomeruli compared to the right kidney. A negative correlation was found between warm ischemia time and glomerular number. Conclusions: About one quarter of glomeruli was lost after 30 minutes of renal warm ischemia. No glomeruli loss was detected before 20 minutes of warm ischemia. However, progressive glomerular loss was associated with increasing warm ischemia time.

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Section: ■ Discussionmentioning

confidence: 99%

The relationship between renal warm ischemia time and glomerular loss. An experimental study in a pig model

et al. 2017

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confidence: 93%

“…The mechanism of reduced nephron endowment in dexamethasone or ethanol exposure has been suggested to be inhibited branching morphogenesis in an organ culture study (5,7). Reduced ureteric branching has recently been reported in a model of maternal hyperglycemia in vivo (8).Another possible mechanism of reduced nephron number is early cessation of nephrogenesis. In human premature infants, nephrogenesis is reported to continue only up to 40 d after birth (9).…”

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Maternal nutrient restriction inhibits ureteric bud branching but does not affect the duration of nephrogenesis in rats

Awazu

Hida

2015

Pediatr Res

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Background: Maternal nutrient restriction produces offspring with fewer nephrons. We studied whether the reduced nephron number is due to the inhibition of ureteric branching or early cessation of nephrogenesis in rats. Signaling pathways involved in kidney development were also examined. Methods: The offspring of dams given food ad libitum (control (CON)) and those subjected to 50% food restriction (nutrient restriceted (NR)) were examined. results: At embryonic day 13 (E13), there was no difference between NR and CON in body weight or kidney size. Ureteric buds branched once in both NR and CON. At E14 and E15, body and kidney size were significantly reduced in NR. Ureteric bud tip numbers were also reduced to 50% of CON. On the other hand, the disappearance of nephrogenic zone and a nephron progenitor marker Cited1 was not different between CON and NR. The final glomerular number of NR was 80% of CON. Activated extracellular signal-regulated kinase (ERK), p38, PI3K, Akt, and mammallian target of rapamycin (mTOR), and protein expression of β-catenin were downregulated at E15. conclusion: Ureteric branching is inhibited and developmentally regulated signaling pathways are downregulated at an early stage by maternal nutrient restriction. These changes, not early cessation of nephrogenesis, may be a mechanism for the inhibited kidney growth and nephrogenesis. t he concept that disturbed intrauterine organogenesis affects the health and disease in the adulthood, termed developmental origins of health and disease, has been increasingly recognized. With respect to the kidney, low birth weight is associated with a risk for hypertension and renal disease, and reduced nephron number is considered to be the cause. In animals, maternal protein or global nutrient restriction, uterine artery ligation, hyperglycemia, and exposure to various agents such as glucocorticoids or alcohol produce offspring with fewer nephrons (1-6). Depletion of stem cells by increased apoptosis has been suggested to be responsible for the decreased nephron formation (1,3). On the other hand, ureteric bud branching is a fundamental step in determining nephron number. The mechanism of reduced nephron endowment in dexamethasone or ethanol exposure has been suggested to be inhibited branching morphogenesis in an organ culture study (5,7). Reduced ureteric branching has recently been reported in a model of maternal hyperglycemia in vivo (8).Another possible mechanism of reduced nephron number is early cessation of nephrogenesis. In human premature infants, nephrogenesis is reported to continue only up to 40 d after birth (9). These infants are under various stresses including hypoxia, infection, and medications adversely affecting nephrogenesis. It has been postulated that adverse conditions during development promote differentiation aiming at early maturation and survival at the expense of reduced organ growth. Newborn rats resemble human premature neonates in that nephrogenesis continues after birth. Early cessation of nephrogenesis, therefore, may b...

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“…Reading those case-specific coordinates according to the schema introduced here (Table 1; Fig. 5b, c), in combination with modern computer-assisted techniques such as laser scanning immunohistochemistry or optical projection tomography could help to more precisely separate an inactive from active status of the nephrogenic zone and integrated niches [65-67]. …”

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confidence: 99%

Reading First Coordinates from the Nephrogenic Zone in Human Fetal Kidney

Minuth¹

2017

Nephron

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While substantial information is available on organ anlage and the primary formation of nephrons, molecular mechanisms acting during the late development of the human kidney have received an astonishing lack of attention. In healthy newborn babies, nephrogenesis takes place unnoticed until birth. Upon delivery, morphogenetic activity in the nephrogenic zone decreases, and the stem cell niches aligned beyond the organ capsule vanish by an unknown signal. However, this signal also plays a key role in preterm and low birth weight babies. Although they are born in a phase of active nephrogenesis, pathological findings illustrate that they evolve to a high incidence oligonephropathy and prematurity of renal parenchyma. Different extra- and intrauterine influences seem to be responsible, but independent from chemical nature, all of them culminate in the nephrogenic zone. One assumes that the marred development is caused either by an overshoot of metabolites, misleading signaling of morphogens, unbalanced synthesis of extracellular matrix or restricted contact between mesenchymal and epithelial stem cells. Even more surprising is that there is only a few vague morphological information of the nephrogenic zone in the human fetal kidney available and ultrastructural data is severely lacking. On this account, the first coordinates were determined by optical microscopy and morphometry. Without claiming to be complete, generated results made it possible to create schematic illustrations true to scale for orientation. It will help graduating students, young pediatricians, pathologists, and scientists working in the field of biomedicine to interpret professionally the nephrogenic zone and contained niches.

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Altered Ureteric Branching Morphogenesis and Nephron Endowment in Offspring of Diabetic and Insulin-Treated Pregnancy

Cited by 56 publications

References 54 publications

The relationship between renal warm ischemia time and glomerular loss. An experimental study in a pig model

The relationship between renal warm ischemia time and glomerular loss. An experimental study in a pig model

Maternal nutrient restriction inhibits ureteric bud branching but does not affect the duration of nephrogenesis in rats

Reading First Coordinates from the Nephrogenic Zone in Human Fetal Kidney

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