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

Minuth, Will W.

doi:10.1186/s40348-021-00120-0

Cited by 3 publications

(8 citation statements)

References 43 publications

(87 reference statements)

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“…4d). Recent investigations additionally demonstrated that each of the listed stages exhibits a different shape, is recognized within personal coordinates, and is facing individual parts of the structural neighbors [12,19,20]. This again shows that each stage of nephron anlage is exposed to a typical claim of the interjacent interstitium, which can exhibit existing, evolving, transient, degrading, or lasting properties (Fig.…”

Section: Translocation Between Interstitial Workbenchesmentioning

confidence: 88%

“…From the kidneys of preterm and low birth babies, it is known that noxae provoke the reduction in width of the nephrogenic zone [6]. Although it has not been closely investigated, one must assume that the loss of tissue concerns not only the stages of nephron anlage but also the structural neighbors such as the CD ampullae, the sprouting microvessels, the establishing interstitium, and probably also the renal capsule [12]. As a consequence, it is highly important to develop a deeper understanding of these details, when the interstitium is seen as an instance that masters the formation of a nephron or when this process is harmed by the noxae impairing nephrogenesis [4,14,21,24].…”

Section: Narrow Interstitial Cleft At the Medial Aspect Of The Develo...mentioning

confidence: 99%

“…However, it is of great importance to have a clear understanding of the intactness and the respective damage, since the development of a nephron is not an isolated and autonomously running process. In fact, it depends on intact tissue and cell-to-cell interactions [8,9] such as the spatial and temporal exchange of morphogenic proteins [10,11] and the mutual patterning with its structural neighbors [12].…”

Section: Introductionmentioning

confidence: 99%

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The interstitium at the developing nephron in the fetal kidney during advanced pregnancy — a microanatomical inventory

Minuth

2022

Mol Cell Pediatr

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Background A series of noxae can evoke the termination of nephron formation in preterm and low birth weight babies. This results in oligonephropathy with severe consequences for health in the later life. Although the clinical parameters have been extensively investigated, little is known about the initial damage. Previous pathological findings indicate the reduction in width of the nephrogenic zone and the lack of S-shaped bodies. Current morphological investigations suggest that due to the mutual patterning beside the forming nephron, also its structural neighbors, particularly the interjacent interstitium, must be affected. However, beside the findings on integrative and mastering functions, systematic microanatomical data explaining the configuration of the interstitium at the developing nephron in the fetal kidney during advanced pregnancy is not available. Therefore, this work explains the typical features. Results The generated data depicts that the progenitor cells, nephrogenic niche, pretubular aggregate, and mesenchymal-to-epithelial transition are restricted to the subcapsular interstitium. During the proceeding development, only the distal pole of the renal vesicles and comma- and S-shaped bodies stays in further contact with it. The respective proximal pole is positioned opposite the peritubular interstitium at the connecting tubule of an underlying but previously formed nephron. The related medial aspect faces the narrow peritubular interstitium of a collecting duct (CD) ampulla first only at its tip, then at its head, conus, and neck, and finally at the differentiating CD tubule. The lateral aspect starts at the subcapsular interstitium, but then it is positioned along the wide perivascular interstitium of the neighboring ascending perforating radiate artery. When the nephron matures, the interstitial configuration changes again. Conclusions The present investigation illustrates that the interstitium at the forming nephron in the fetal kidney consists of existing, transient, stage-specific, and differently far matured compartments. According to the developmental needs, it changes its shape by formation, degradation, fusion, and rebuilding.

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Section: Translocation Between Interstitial Workbenchesmentioning

confidence: 88%

Section: Narrow Interstitial Cleft At the Medial Aspect Of The Develo...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The interstitium at the developing nephron in the fetal kidney during advanced pregnancy — a microanatomical inventory

Minuth

2022

Mol Cell Pediatr

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“…Numerous studies have investigated the development of the tubular portion and the entire nephron from different perspectives [Osathanondh and Potter, 1966;Saxén and Sariola, 1987;Dakovic-Bjelakovic et al, 2005;Faa et al, 2012;Song et al, 2012;Minuth, 2021]. However, only one study quantified the development of renal tubules in the kidney cortex of human foetuses at different GAs and reported a gradual increase in their volume density [Dakovic-Bjelakovic et al, 2005].…”

Section: Discussionmentioning

confidence: 99%

“…The expressions of Ki-67, Bcl-2, and Bax have been investigated in developing nephrons allocated to the nephrogenic, maturation, and mature zones of the foetal kidney cortex [Minuth, 2020[Minuth, , 2021. The distribution and staining intensity of immunopositive cells were independently assessed by 2 pathologists in all cases.…”

Section: Immunohistochemical Methodsmentioning

confidence: 99%

Developmental Characteristics of the Glomerular and Tubular Portion of the Nephron in the Human Foetal Kidney Cortex: Morphometrical and Immunohistochemical Analysis

Antic¹,

Bjelaković²,

Petrović³

et al. 2022

Cells Tissues Organs

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This study aimed to morphometrically examine the development of glomeruli and tubules in the kidney cortex of human foetuses at different gestational ages (GAs). We also investigated the expression of the proliferation marker Ki-67 and apoptosis-related markers Bcl-2 and Bax during nephrogenesis using immunohistochemistry. Kidney samples from 38 human foetuses of both sexes with GA ranging from 13 to 40 weeks were analysed. The average area, perimeter, and Feret's diameter of the glomeruli gradually decreased up to a period of 29–32 weeks of gestation and subsequently increased until a period of 37–40 weeks. There was a weak negative correlation with GA. In contrast, the areal density of glomeruli increased up to a period of 21–24 weeks and then gradually decreased until a period of 37–40 weeks, showing a moderate negative correlation with GA. The average area of renal tubules slightly decreased until a period of 21–24 weeks of gestation and then gradually increased until a period of 36–40 weeks, showing a moderate positive correlation with GA. The average areal density of renal tubules increased significantly until a period of 21–24 weeks of gestation, remained relatively constant until a period of 33–36 weeks, and then increased significantly at 36–40 weeks. There was a strong positive correlation with GA. Our results showed that Ki-67 was expressed in numerous cells of the metanephric mesenchyme, pretubular aggregates, renal vesicles, comma-shaped bodies, and early S-shaped bodies. During subsequent development the expression of Ki-67 was markedly reduced. Similarly, Bcl-2 was strongly expressed in induced nephrogenic progenitor cells, pretubular aggregates, renal vesicles, and comma-shaped bodies. As vascularisation and maturation of the nephron proceeded, Bcl-2 staining became less intense and limited. Weak Bax expression was observed in individual scattered cells within segments of the nephrons at all developmental stages.

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Installation of the developing nephron in the fetal human kidney during advanced pregnancy

Minuth

2023

Mol Cell Pediatr

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Background The kidneys of preterm and low birth weight babies reflect vulnerability, since several noxae can evoke the termination of nephron formation. This again leads to oligonephropathy with severe consequences for health in the later life. While the clinical parameters have been intensely investigated, only little is known about the initial traces left by the noxae. For the fetal human kidney, solely the lack of basophilic S-shaped bodies and the reduction in width of the nephrogenic zone were registered. It is not known in how far also the involved progenitor cells, the earlier nephron stages, the collecting duct (CD) ampullae, and the local interstitium are collaterally harmed. Aim The interstitium at the forming nephron is heterogeneously structured. Thereby, it fulfills quite different mastering and integrative tasks. Since data dealing with the installation of a nephron is not available, the microanatomical features were recorded. Results The microscopic specimens show that the installation of the transient stages of nephron anlage is not synchronized. Instead, it is controlled within a nephrogenic compartment of the nephrogenic zone. It starts near the renal capsule by positioning the nephrogenic niche so that the nephrogenic progenitor cells face the epithelial progenitor cell at the tip of a CD ampulla. Then, the induced nephrogenic progenitor cells assimilate in the pretubular aggregate. While its medial part remains opposite the head of the CD ampulla, at its proximal end, the primitive renal vesicle is formed. Only a part of it separates to stick to the section border between the head and conus of the CD ampulla. This marks the link with the future connecting tubule at the distal pole of the extending renal vesicle. Meanwhile, the proximal pole is mounted next to the connecting tubule of an earlier developed nephron. The resulting two-point mounting serves a common elongation of the conus at the CD ampulla and the medial aspect of the comma-shaped body. In the S-shaped body, it supports to defoliate the arising glomerulus and to link it with the perforating radiate artery at its deep lateral aspect. Conclusions The investigation depicts that the installation is an interactive process between the stages of nephron anlage and its structural neighbors. A special meaning has the interjacent interstitium. It is vital for the positioning, shaping, and physiological integration. Due to its special location, this is mainly exposed to noxae.

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

Cited by 3 publications

References 43 publications

The interstitium at the developing nephron in the fetal kidney during advanced pregnancy — a microanatomical inventory

The interstitium at the developing nephron in the fetal kidney during advanced pregnancy — a microanatomical inventory

Developmental Characteristics of the Glomerular and Tubular Portion of the Nephron in the Human Foetal Kidney Cortex: Morphometrical and Immunohistochemical Analysis

Installation of the developing nephron in the fetal human kidney during advanced pregnancy

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