Nephron Number in the Offspring of Rats Fed a Low Protein Diet During Pregnancy

Zimanyi, Monika A.; Bertram, John F.; Black, Jane M.

doi:10.5566/ias.v19.p219-222

Cited by 20 publications

(4 citation statements)

References 17 publications

(20 reference statements)

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“…Human studies have identified a strong linear relationship between birth weight and nephron number [39], [40], [41]. Animal models of spontaneous [42], [43] and induced growth restriction [42], [44], [45] further support this association. In rodents, high glucose exposure is reported to alter kidney morphology and lead to a nephron deficit in growth restricted and normal birth weight offspring [16], [17].…”

Section: Discussionmentioning

confidence: 78%

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

et al. 2013

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There is strong evidence from human and animal models that exposure to maternal hyperglycemia during in utero development can detrimentally affect fetal kidney development. Notwithstanding this knowledge, the precise effects of diabetic pregnancy on the key processes of kidney development are unclear due to a paucity of studies and limitations in previously used methodologies. The purpose of the present study was to elucidate the effects of hyperglycemia on ureteric branching morphogenesis and nephrogenesis using unbiased techniques. Diabetes was induced in pregnant C57Bl/6J mice using multiple doses of streptozotocin (STZ) on embryonic days (E) 6.5-8.5. Branching morphogenesis was quantified ex vivo using Optical Projection Tomography, and nephrons were counted using unbiased stereology. Maternal hyperglycemia was recognised from E12.5. At E14.5, offspring of diabetic mice demonstrated fetal growth restriction and a marked deficit in ureteric tip number (control 283.7±23.3 vs. STZ 153.2±24.6, mean±SEM, p<0.01) and ureteric tree length (control 33.1±2.6 mm vs. STZ 17.6±2.7 mm, p = 0.001) vs. controls. At E18.5, fetal growth restriction was still present in offspring of STZ dams and a deficit in nephron endowment was observed (control 1246.2±64.9 vs. STZ 822.4±74.0, p<0.001). Kidney malformations in the form of duplex ureter and hydroureter were a common observation (26%) in embryos of diabetic pregnancy compared with controls (0%). Maternal insulin treatment from E13.5 normalised maternal glycaemia but did not normalise fetal weight nor prevent the nephron deficit. The detrimental effect of hyperglycemia on ureteric branching morphogenesis and, in turn, nephron endowment in the growth-restricted fetus highlights the importance of glycemic control in early gestation and during the initial stages of renal development.

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Section: Discussionmentioning

confidence: 78%

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

et al. 2013

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“…It is well known that a range of genetic factors and perturbations to the fetal-maternal environment 52,53 can influence nephron endowment at birth. Fetal-maternal factors include maternal nutrition, 54 –56 gestational diabetes, 57 exposure to alcohol, 58,59 natural and synthetic glucocorticoids, 60 and hypoxia. 61,62 Little is known about regulation of podocytogenesis and podocyte endowment at birth, although we recently reported that mild hypoxia in mice during gestation gives rise to male offspring with low podocyte endowment, although female offspring were not affected.…”

Section: Discussionmentioning

confidence: 99%

Podometrics in Japanese Living Donor Kidneys: Associations with Nephron Number, Age, and Hypertension

Haruhara

Sasaki

Zoysa

et al. 2021

JASN

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BackgroundPodocyte depletion, low nephron number, aging, and hypertension are associated with glomerulosclerosis and CKD. However, the relationship between podometrics and nephron number has not previously been examined.MethodsTo investigate podometrics and nephron number in healthy Japanese individuals, a population characterized by a relatively low nephron number, we immunostained single paraffin sections from 30 Japanese living-kidney donors (median age, 57 years) with podocyte-specific markers and analyzed images obtained with confocal microscopy. We used model-based stereology to estimate podometrics, and a combined enhanced–computed tomography/biopsy-specimen stereology method to estimate nephron number.ResultsThe median number of nonsclerotic nephrons per kidney was 659,000 (interquartile range [IQR], 564,000–825,000). The median podocyte number and podocyte density were 518 (IQR, 428–601) per tuft and 219 (IQR, 180–253) per 106μm3, respectively; these values are similar to those previously reported for other races. Total podocyte number per kidney (obtained by multiplying the individual number of nonsclerotic glomeruli by podocyte number per glomerulus) was 376 million (IQR, 259–449 million) and ranged 7.4-fold between donors. On average, these healthy kidneys lost 5.63 million podocytes per kidney per year, with most of this loss associated with glomerular loss resulting from global glomerulosclerosis, rather than podocyte loss from healthy glomeruli. Hypertension was associated with lower podocyte density and larger podocyte volume, independent of age.ConclusionsEstimation of the number of nephrons, podocytes, and other podometric parameters in individual kidneys provides new insights into the relationships between these parameters, age, and hypertension in the kidney. This approach might be of considerable value in evaluating the kidney in health and disease.

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“…Observational studies in the USA have reported that body weight and WC were reduced when protein was consumed above the recommended daily allowance [0.8 g/kg body weight (BW)] [53]. It has been noted in animal models, that pregnant rats consuming a low protein diet were more prone to GDM and to having offspring with a low birthweight [54, 55]. In our study, we found a significant interaction between the metabolic-GRS and protein energy (%) on log WC, where individuals consuming a low protein diet, despite carrying 5 or more risk alleles, had a lower waist to hip ratio compared to individuals carrying 4 or less risk alleles.…”

Section: Discussionmentioning

confidence: 99%

A nutrigenetic approach for investigating the relationship between vitamin B12 status and metabolic traits in Indonesian women

Surendran

Aji

Ariyasra

et al. 2019

J Diabetes Metab Disord

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PurposeAdverse effects of maternal vitamin B12 deficiency have been linked to major clinical outcomes, including increased body mass index and gestational diabetes, however, less is known about vitamin B12 nutrition in non-pregnant women. Hence, the aim of the present study was to explore the relationships between metabolic traits and vitamin B12 status in a cohort of healthy Indonesian women and to investigate whether these relationships were modified by dietary intake using a genetic approach.MethodsA total of 117 Minangkabau women (aged 25–60 years), from the city of Padang, West Sumatra underwent anthropometric, biochemical, dietary intake analysis and genetic tests. Genetic risk scores (GRS) based on nine vitamin B12 associated single nucleotide polymorphisms (SNPs) (B12-GRS) and nine metabolic SNPs (metabolic-GRS) were constructed.ResultsThe B12-GRS and metabolic-GRS had no effect on vitamin B12 (P > 0.160) and metabolic traits (P > 0.085). However, an interaction was observed between the B12-GRS and dietary fibre intake (g) on glycated haemoglobin (HbA1C) levels (P interaction = 0.042), where among those who consumed a low fibre diet (4.90 ± 1.00 g/day), individuals carrying ≥9 risk alleles for vitamin B12 deficiency had significantly higher HbA1C levels (P = 0.025) compared to those carrying ≤8 risk alleles.ConclusionOur study showed a significant impact of the B12-GRS on HbA1C concentrations through the influence of a dietary factor, however, our study failed to provide evidence for an impact of metabolic-GRS on lowering B12 concentrations. Further replication studies utilizing larger sample sizes are needed to confirm our findings.Electronic supplementary materialThe online version of this article (10.1007/s40200-019-00424-z) contains supplementary material, which is available to authorized users.

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Nephron Number in the Offspring of Rats Fed a Low Protein Diet During Pregnancy

Cited by 20 publications

References 17 publications

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

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

Podometrics in Japanese Living Donor Kidneys: Associations with Nephron Number, Age, and Hypertension

A nutrigenetic approach for investigating the relationship between vitamin B12 status and metabolic traits in Indonesian women

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