Key features of the nephrogenic zone in the fetal human kidney—hardly known but relevant for the detection of first traces impairing nephrogenesis

Minuth, Will W.

doi:10.1007/s00441-018-2937-4

Cited by 7 publications

(12 citation statements)

References 89 publications

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“…The activity of the nephrogenic zone is critical for nephrogenesis [30]. Since neonatal hyperoxia disrupted tubular development as observed above, it is important to evaluate the effect of hyperoxia on the nephrogenic zone.…”

Section: Resultsmentioning

confidence: 99%

Proximal Tubular Development Is Impaired with Downregulation of MAPK/ERK Signaling, HIF-1α, and Catalase by Hyperoxia Exposure in Neonatal Rats

You

2019

Oxidative Medicine and Cellular Longevity

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Supplemental oxygen therapy (hyperoxia) is a widely used treatment for alveolar hypoxia in preterm infants. Despite being closely monitored, hyperoxia exposure is believed to undermine neonatal nephrogenesis and renal function caused by elevated oxidative stress. Previous studies have mostly focused on the hyperoxia-induced impairment of glomerular development, while the long-term impact of neonatal hyperoxia on tubular development and the regulatory component involved in this process remain to be clarified. Here, we examined tubular histology and apoptosis, along with the expression profile of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling, hypoxia-inducible factor 1α (HIF-1α), and catalase, following hyperoxia exposure in neonatal rats. Hematoxylin and eosin (H&E) staining revealed the early disappearance of the nephrogenic zone, as well as dilated lumens and reduced epithelial cells, of mature proximal tubules following neonatal hyperoxia. A robust increase in tubular cell apoptosis caused by neonatal hyperoxia was found using a TUNEL assay. Moreover, neonatal hyperoxia altered renal MAPK/ERK signaling activity and downregulated the expression of HIF-1α and catalase in the proximal tubules throughout nephrogenesis from S-shaped bodies to mature proximal tubules. Cell apoptosis in the proximal tubules was positively correlated with HIF-1α expression on the 14th postnatal day. Our data indicates that proximal tubular development is impaired by neonatal hyperoxia, which is accompanied by altered MAPK/ERK signaling as well as downregulated HIF-1α and catalase. Therapeutic management that targets MAPK/ERK signaling, HIF-1α, or catalase may serve as a protective agent against hyperoxia-induced oxidative damage to neonatal proximal tubules.

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Section: Resultsmentioning

confidence: 99%

Proximal Tubular Development Is Impaired with Downregulation of MAPK/ERK Signaling, HIF-1α, and Catalase by Hyperoxia Exposure in Neonatal Rats

You

2019

Oxidative Medicine and Cellular Longevity

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“…Within the last years, a series of viable options have been proposed with regard to aiding regeneration of renal parenchyma [54]. In order to keep our goals realistic, the task for the next decade will be to transfer our current knowledge on the specific development of the nephrogenic zone and the here contained stages of nephron anlage from the rodent kidney to the fetal human kidney [36,55]. For these reasons, it is understandable that a concept for a reliable prolongation of nephrogenesis is not yet in sight.…”

Section: Discussionmentioning

confidence: 99%

“…The outer cortex of the fetal human kidney consists of the external nephrogenic zone and the underlying maturation zone (Table 1) [36,37]. Both extend along the entire surface of each kidney lobe [38,39].…”

Section: Structure Of the Nephrogenic Zonementioning

confidence: 99%

Shaping of the nephron – a complex, vulnerable, and poorly explored backdrop for noxae impairing nephrogenesis in the fetal human kidney

Minuth

2020

Mol Cell Pediatr

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Background: The impairment of nephrogenesis is caused by noxae, all of which are significantly different in molecular composition. These can cause an early termination of nephron development in preterm and low birth weight babies resulting in oligonephropathy. For the fetal human kidney, there was no negative effect reported on the early stages of nephron anlage such as the niche, pretubular aggregate, renal vesicle, or comma-shaped body. In contrast, pathological alterations were identified on subsequently developing S-shaped bodies and glomeruli. While the atypical glomeruli were closely analyzed, the S-shaped bodies and the pre-stages received little attention even though passing the process of nephron shaping. Since micrographs and an explanation about this substantial developmental period were missing, the shaping of the nephron in the fetal human kidney during the phase of late gestation was recorded from a microanatomical point of view. Results: The nephron shaping starts with the primitive renal vesicle, which is still part of the pretubular aggregate at this point. Then, during extension of the renal vesicle, a complex separation is observed. The medial part of its distal pole is fixed on the collecting duct ampulla, while the lateral part remains connected with the pretubular aggregate via a progenitor cell strand. A final separation occurs, when the extended renal vesicle develops into the comma-shaped body. Henceforth, internal epithelial folding generates the tubule and glomerulus anlagen. Arising clefts at the medial and lateral aspect indicate an asymmetrical expansion of the S-shaped body. This leads to development of the glomerulus at the proximal pole, whereas in the center and at the distal pole, it results in elongation of the tubule segments. Conclusions: The present investigation deals with the shaping of the nephron in the fetal human kidney. In this important developmental phase, the positioning, orientation, and folding of the nephron occur. The demonstration of previously unknown morphological details supports the search for traces left by the impairment of nephrogenesis, enables to refine the assessment in molecular pathology, and provides input for the design of therapeutic concepts prolonging nephrogenesis.

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“…Covered by the renal capsule, it is built up by transverse layers of embryonic, maturing, and matured parenchyma and stroma. In the external nephrogenic zone, the process of nephron formation starts [ 9 ] and can be recognized by the transient stages of nephron anlage [ 10 , 11 ]. In the subjacent maturation zone, the conversion of the S-shaped body as the last stage of nephron anlage into the lasting nephron occurs.…”

Section: Introductionmentioning

confidence: 99%

The mutual patterning between the developing nephron and its covering tissues—valid reasons to rethink the search for traces left by impaired nephrogenesis

Minuth

2021

Mol Cell Pediatr

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Background The impairment of nephrogenesis can cause the termination of nephron formation in preterm and low birth weight babies. This leads to oligonephropathy with severe health consequences in later life. Although many clinical parameters are known, surprisingly little information is available regarding the initial damage on the developing nephron. Equally astounding, the first morphological data regarding the specifics of nephron formation in the nephrogenic zone of the fetal human kidney during late gestation has only been published within the past few years. In this context, it was observed that each stage of nephron anlage is surrounded by a specific set of tissues. Although highly relevant for the normal progress of nephron formation, the mutual patterning has not been systematically described. Results To contribute, the different stages of nephron anlage in the nephrogenic zone of the fetal human kidney during late gestation were screened by the optical microscope and documented by images. Following this, magnifications (28 × 18 cm) were produced to trace the contours of the developing nephron and its covering tissues. The resulting sketches, almost true to scale, were scanned, edited, and processed by a design program. As a base, first the individual position, size, and shape of the nephrogenic niche, pretubular aggregate, renal vesicles, comma- and S-shaped bodies are presented. Secondly, their structural relations to the renal capsule, collecting duct ampulla, perforating radiate artery, and expanding interstitium are shown. Third of all, the focus is on less considered configurations, such as site-specific approximation, local distancing, punctual adhesion, integration, separation, delamination, formation of congruent and divergent surfaces, and folding and opening of interstitial clefts. Conclusions The present contribution illuminates the mutual patterning between the developing nephron and its covering tissues. It is indispensable to know about the microanatomical relations, in order to identify whether the noxae impairing nephrogenesis targets only the developing nephron or also its covering tissues as interacting and controlling instances.

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Key features of the nephrogenic zone in the fetal human kidney—hardly known but relevant for the detection of first traces impairing nephrogenesis

Cited by 7 publications

References 89 publications

Proximal Tubular Development Is Impaired with Downregulation of MAPK/ERK Signaling, HIF-1α, and Catalase by Hyperoxia Exposure in Neonatal Rats

Proximal Tubular Development Is Impaired with Downregulation of MAPK/ERK Signaling, HIF-1α, and Catalase by Hyperoxia Exposure in Neonatal Rats

Shaping of the nephron – a complex, vulnerable, and poorly explored backdrop for noxae impairing nephrogenesis in the fetal human kidney

The mutual patterning between the developing nephron and its covering tissues—valid reasons to rethink the search for traces left by impaired nephrogenesis

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