scholarly journals Quantitative analysis of the nephron during human fetal kidney development

2005 ◽  
Vol 62 (4) ◽  
pp. 281-286 ◽  
Author(s):  
Marija Dakovic-Bjelakovic ◽  
Slobodan Vlajkovic ◽  
Rade Cukuranovic ◽  
Svetlana Antic ◽  
Goran Bjelakovic ◽  
...  

Background. The development of human kidney is a complex process. The number, shape, size, and distribution of nephrons as functional units in a kidney, provide some important information about the organization of the kidney. The aim of this study was to extend the knowledge of the developing human kidney by studying nephrons in the kidney's cortex during gestation. Methods. Kidney tissue specimens of 32 human fetuses, the gestational age from IV lunar month (LM IV) to LM X, were analyzed. Specimens were divided in ten groups based on gestational age. Stereological methods were used at the light microscopic level to estimate the volume densities of the corpuscular and tubular components of the nephron in the cortex of the developing human kidney. Results. Nephron polymorphism was the main characteristic of the human fetal kidney during development. In younger fetuses, just below the renal capsule, there was a wide nephrogenic zone. It contained the condensed mesenchyme and terminal ends of the ureteric bud. Nephrons, in the different stages of development, were located around the ureteric bud which branched in the cortical nephrogenic zone and induced nephrogenesis. More mature nephrons were located in the deeper part of the cortex, close to the juxta-medullary junction. During gestation, nephrogenesis continually advanced, and the number of nephrons increased. Glomeruli changed their size and shape, while the tubules changed their length and convolution. Renal cortex became wider and contained the more mature glomeruli and the more convoluted tubules. The volume density of the tubular component of the nephron increased continually from 10.53% (LM IVa) to 27.7% (LM X). Renal corpuscles changed their volume density irregularly during gestation, increasing from 13% (LM IVa) to 15.5% (LM IVb). During the increase of gestational age, the volume density of corpuscular component of the nephron decreased to 11.7% (LM VIII), then went on increasing until the end of the intrauterine development (LM X) when corpuscles occupied 16.73% of the cortical volume. The volume density of the developing nephrons (corpuscular and tubular portion) showed the significant positive correlation (r = 0.85; p<0.01) with gestational age. Conclusion. The present study was one of few quantitative studies of the human developing nephron. Knowledge about the normal development of the human kidney should be important for the future medical practice.

PLoS Biology ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. e3000152 ◽  
Author(s):  
Mazène Hochane ◽  
Patrick R. van den Berg ◽  
Xueying Fan ◽  
Noémie Bérenger-Currias ◽  
Esmée Adegeest ◽  
...  

2019 ◽  
Vol 207 (2) ◽  
pp. 69-82 ◽  
Author(s):  
Will W. Minuth

Clinical aspects dealing with the impairment of nephrogenesis in preterm and low birth weight babies were intensely researched. In this context it was shown that quite different noxae can harm nephron formation, and that the morphological damage in the fetal kidney is rather complex. Some pathological findings show that the impairment leads to changes in developing glomeruli that are restricted to the maturation zone of the outer cortex in the fetal human kidney. Other data show also imprints on the stages of nephron anlage including the niche, the pretubular aggregate, the renal vesicle, and comma- and S-shaped bodies located in the overlying nephrogenic zone of the rodent and human kidneys. During our investigations it was noticed that the stages of nephron anlage in the fetal human kidney during the phase of late gestation have not been described in detail. To contribute, these stages were recorded along with corresponding images. The initial nephron formation in the rodent kidney served as a reference. Finally, the known imprints left by the impairment in both specimens were listed and discussed. In sum, the relatively paucity of data on nephron formation in the fetal human kidney during the late phase of gestation is a call to start with intense research so that concepts for a therapeutic prolongation of nephrogenesis can be designed.


2015 ◽  
Vol 30 (suppl_3) ◽  
pp. iii86-iii86
Author(s):  
Marija Bjelakovic ◽  
Slobodan Vlajkovic ◽  
Goran Bjelakovic

2004 ◽  
Vol 286 (4) ◽  
pp. F625-F633 ◽  
Author(s):  
P. Vrljicak ◽  
D. Myburgh ◽  
A. K. Ryan ◽  
M. A. van Rooijen ◽  
C. L. Mummery ◽  
...  

Signaling by the transforming growth factor (TGF)-β superfamily is important during kidney development. Here, we describe the spatial and temporal expression patterns of the Smads, the transcription factors that translate TGF-β signals into gene expression. RT-PCR data and in situ hybridization analysis showed that the receptor-regulated (R) Smads (Smad1, -2, -3, -5, and -8), the common partner Smad (Smad4), and the inhibitory (I) Smads (Smad6 and -7) were all expressed during mouse kidney development from embryonic day 12 until the end of nephrogenesis at postnatal day 15. Each Smad had a distinct spatial distribution. All were expressed by mesenchymal cells in the nephrogenic zone and were downregulated once these cells began to epithelialize. The common partner Smad, Smad4, was present in uninduced mesenchymal cells and at ureteric bud tips. The bone morphogenetic-responsive R-Smads, Smad1, -5, and -8, were mainly expressed in the nephrogenic zone, whereas the TGF-β- responsive R-Smads were predominantly noted in the medullary interstitium. Expression of the I-Smad Smad7 was also seen in mesenchymal cells in the interstitium. Based on the observed patterns of expression, we speculate that individual or combinations of Smads may play specific roles in cell-fate determination during kidney development.


1984 ◽  
Vol 10 (1-2) ◽  
pp. 13-22
Author(s):  
M.Linette Casey ◽  
John M. Johnston ◽  
Paul C. MacDonald

2005 ◽  
Vol 62 (2) ◽  
pp. 107-11 ◽  
Author(s):  
Slobodan Vlajkovic ◽  
Marija Dakovic-Bjelakovic ◽  
Rade Cukuranovic ◽  
Jasmina Popovic

Background. Human fetal kidney is quite different from the mature kidney, both macroscopically and hystologically. Lobulated surface of the human fetal kidney reflects its inner organization. Aim. To determine the fetal kidneys' volume according to the gestational age, to establish periods of their maximal and minimal growth and to compare these values for various gestational ages. Methods. Forty five human fetal kidneys aged from IV to X lunar months were analyzed. Kidneys were divided into nine groups according to their gestational age. The volumes of cortex and medulla were determined using stereological methods. The results were statistically analyzed and the periods of significant growth of these structures were marked. Results. Fetal kidney's cortex and medulla grew continually with a very high coefficient of linear correlation with crown-rump length. The cortex/medulla ratio was minimal in the first half of V lunar month, when medulla grew most rapidly and it was maximal immediately before birth, when cortex achieved its maximum. Conclusion. This study was an effort to provide some parameters which would help in the future investigations of the development of human fetal kidney.


2019 ◽  
Author(s):  
Yishay Wineberg ◽  
Itamar Kanter ◽  
Nissim Ben-Haim ◽  
Naomi Pode-Shakked ◽  
Efrat Bucris ◽  
...  

ABSTRACTNephrons are the functional units of the kidney. During kidney development, cells from the cap mesenchyme – a transient kidney-specific progenitor state – undergo a mesenchymal to epithelial transition (MET) and subsequently differentiate into the various epithelial cell types that create the tubular structures of the nephron. Faults in this transition can lead to a pediatric malignancy of the kidney called Wilms’ tumor that mimics normal kidney development. While kidney development has been characterized at the gene expression level, a comprehensive characterization of alternative splicing is lacking. We therefore performed RNA sequencing on cell populations representing early, intermediate, and late developmental stages of the human fetal kidney, as well as three blastemal-predominant Wilms’ tumor patient-derived xenografts. We identified a set of transcripts that are alternatively spliced between the different developmental stages. Moreover, we found that cells from the earliest developmental stage have a mesenchymal splice-isoform profile that is similar to that of blastemal-predominant Wilms’ tumors. RNA binding motif enrichment analysis suggests that the mRNA binding proteins ESRP1, ESRP2, RBFOX2, and QKI regulate mRNA splice isoform switching during human kidney development. These findings illuminate new molecular mechanisms involved in kidney development and pediatric kidney tumors.HIGHLIGHTSDuring fetal kidney development, kidney progenitor cells undergo a mesenchymal to epithelial transition (MET) and subsequently differentiate into the various epithelial cell types that create the tubular structures of the nephron.RNA sequencing identifies a set of transcripts that undergo splice isoform switching during the mesenchymal to epithelial transition (MET) that occurs in the course of human fetal kidney development.Cells in the early stages of kidney development have a mesenchymal splice-isoform profile that is similar to that observed in blastemal-predominant Wilms’ tumor patient-derived xenografts (WT-PDX) that represent an aggressive subtype of Wilms’ tumors.RNA binding motif enrichment analysis indicates that the mRNA binding proteins ESRP1, ESRP2, RBFOX2, and QKI regulate splice isoform switching during human kidney development.


Cell Reports ◽  
2018 ◽  
Vol 24 (13) ◽  
pp. 3554-3567.e3 ◽  
Author(s):  
Ping Wang ◽  
Yidong Chen ◽  
Jun Yong ◽  
Yueli Cui ◽  
Rui Wang ◽  
...  

2017 ◽  
Author(s):  
Aneta Przepiorski ◽  
Veronika Sander ◽  
Tracy Tran ◽  
Jennifer A. Hollywood ◽  
Brie Sorrenson ◽  
...  

SummaryKidney organoids generated from human pluripotent stem cells have the potential to revolutionize how kidney development and injury are studied. Current protocols are technically complex and suffer from poor reproducibility and high reagent costs restricting scalability. To overcome these issues, we have established a simple, inexpensive and robust method to grow kidney organoids in bulk from human induced pluripotent stem cells. Our organoids develop tubular structures by day (d) 8 and show optimal tissue morphology at d14. A comparison with fetal human kidney suggests that d14 organoid renal structures most closely resemble ‘capillary loop’ stage nephrons. We show that deletion of HNF1B, a transcription factor linked to congenital kidney defects, interferes with tubulogenesis, validating our experimental system for studying renal developmental biology. Taken together, our protocol provides a fast, efficient and cost-effective method for generating large quantities of human fetal kidney tissue, enabling the study of normal and aberrant human renal development.


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