Skip to main content
Top
Published in: Molecular and Cellular Pediatrics 1/2022

Open Access 01-12-2022 | Research

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

Author: Will W. Minuth

Published in: Molecular and Cellular Pediatrics | Issue 1/2022

Login to get access

Abstract

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.
Literature
2.
go back to reference Dyson A, Kent AL (2019) The effect of preterm birth on renal development and renal health outcome. NeoReviews 20(12):e725–e736PubMedCrossRef Dyson A, Kent AL (2019) The effect of preterm birth on renal development and renal health outcome. NeoReviews 20(12):e725–e736PubMedCrossRef
3.
go back to reference Luyckx VA, Brenner BM (2020) Clinical consequences of developmental programming of low nephron number. Anat Rec (Hoboken) 303(10):2613–2631CrossRef Luyckx VA, Brenner BM (2020) Clinical consequences of developmental programming of low nephron number. Anat Rec (Hoboken) 303(10):2613–2631CrossRef
4.
go back to reference Hoogenboom LA, Wolfs TGAM, Hütten MC, Peutz-Kootstra SMF (2020) Prematurity, perinatal inflammatory stress, and the predisposition to develop chronic kidney disease beyond oligonephropathy. Pediatr Nephrol 36(7):1673–1681PubMedPubMedCentralCrossRef Hoogenboom LA, Wolfs TGAM, Hütten MC, Peutz-Kootstra SMF (2020) Prematurity, perinatal inflammatory stress, and the predisposition to develop chronic kidney disease beyond oligonephropathy. Pediatr Nephrol 36(7):1673–1681PubMedPubMedCentralCrossRef
5.
go back to reference Sutherland MR, Gubhaju L, Moore L, Kent AL, Dahlstrom JE, Horne RSC, Hoy WE, Bertram JF, Black MJ (2011) Accelerated maturation and abnormal morphology in the preterm neonatal kidney. J Am Soc Nephrol 22:1365–1374PubMedPubMedCentralCrossRef Sutherland MR, Gubhaju L, Moore L, Kent AL, Dahlstrom JE, Horne RSC, Hoy WE, Bertram JF, Black MJ (2011) Accelerated maturation and abnormal morphology in the preterm neonatal kidney. J Am Soc Nephrol 22:1365–1374PubMedPubMedCentralCrossRef
6.
go back to reference Rodriguez MM, Gomez AH, Abitbol CL, Chandar JJ, Duara S, Zilleruelo GE (2004) Histomorphogenetic analysis of postnatal glomerulogenesis in extremely preterm infants. Pediatr Dev Pathol 7(1):17–25PubMedCrossRef Rodriguez MM, Gomez AH, Abitbol CL, Chandar JJ, Duara S, Zilleruelo GE (2004) Histomorphogenetic analysis of postnatal glomerulogenesis in extremely preterm infants. Pediatr Dev Pathol 7(1):17–25PubMedCrossRef
7.
go back to reference Black MJ, Sutherland MR, Gubhaju L, Kent AL, Dahlstrom JE, Moore L (2013) When birth comes early: effects on nephrogenesis. Nephrology (Carlton) 18(3):180–182CrossRef Black MJ, Sutherland MR, Gubhaju L, Kent AL, Dahlstrom JE, Moore L (2013) When birth comes early: effects on nephrogenesis. Nephrology (Carlton) 18(3):180–182CrossRef
8.
9.
go back to reference Short KM, Smyth IM (2020) Branching morphogenesis as a driver of renal development. Anat Rec (Hoboken) 303(10):2578–2587CrossRef Short KM, Smyth IM (2020) Branching morphogenesis as a driver of renal development. Anat Rec (Hoboken) 303(10):2578–2587CrossRef
10.
go back to reference Oxburgh L, Muthukrishnan SD, Brown A (2017) Growth factor regulation in the nephrogenic zone of the developing kidney. Results Probl Cell Differ 60:137–164PubMedCrossRef Oxburgh L, Muthukrishnan SD, Brown A (2017) Growth factor regulation in the nephrogenic zone of the developing kidney. Results Probl Cell Differ 60:137–164PubMedCrossRef
11.
go back to reference Rad NK, Aghdami N, Moghadasali R (2020) Cellular and molecular mechanisms of kidney development: from the embryo to the kidney organoid. Front Cell Dev Biol 8:183CrossRef Rad NK, Aghdami N, Moghadasali R (2020) Cellular and molecular mechanisms of kidney development: from the embryo to the kidney organoid. Front Cell Dev Biol 8:183CrossRef
12.
go back to reference Minuth WW (2021) The mutual patterning between the developing nephron and its covering tissues - valid reasons to rethink the search for traces left by impaired nephrogenesis. Mol Cell Pediatr 8(1):9PubMedPubMedCentralCrossRef Minuth WW (2021) The mutual patterning between the developing nephron and its covering tissues - valid reasons to rethink the search for traces left by impaired nephrogenesis. Mol Cell Pediatr 8(1):9PubMedPubMedCentralCrossRef
13.
go back to reference Kobayashi A, Mugford JW, Krautzberger AM, Naimann N, Liao J, McMahon AP (2014) Identification of a multipotent self-renewing stromal progenitor population during mammalian kidney organogenesis. Stem Cell Report 3(4):650–662CrossRef Kobayashi A, Mugford JW, Krautzberger AM, Naimann N, Liao J, McMahon AP (2014) Identification of a multipotent self-renewing stromal progenitor population during mammalian kidney organogenesis. Stem Cell Report 3(4):650–662CrossRef
14.
go back to reference Rowan CJ, Sheybani-Deloui S, Rosenblum ND (2017) Origin and function of the renal stroma in health and disease. Results Probl Cell Difer 60:205–229CrossRef Rowan CJ, Sheybani-Deloui S, Rosenblum ND (2017) Origin and function of the renal stroma in health and disease. Results Probl Cell Difer 60:205–229CrossRef
15.
go back to reference Hum S, Rymer C, Schaefer C, Bushnell D, Sims-Lucas S (2014) Ablation of the renal stroma defines its critical role in nephron progenitor and vascular patterning. PLoS ONE 9(2):e8840CrossRef Hum S, Rymer C, Schaefer C, Bushnell D, Sims-Lucas S (2014) Ablation of the renal stroma defines its critical role in nephron progenitor and vascular patterning. PLoS ONE 9(2):e8840CrossRef
16.
go back to reference Rowan CJ, Li W, Martirosyan H, Erwood S, Hu D, Kim YK, Sheybani-Deloui S, Mulder J, Blake J, Chen L, Rosenblum ND (2018) Hedgehog-GLI signaling in Foxd1-positive stromal cells promotes murine mephrogenesis via TGFβ signaling. Development 154(13):dev159947CrossRef Rowan CJ, Li W, Martirosyan H, Erwood S, Hu D, Kim YK, Sheybani-Deloui S, Mulder J, Blake J, Chen L, Rosenblum ND (2018) Hedgehog-GLI signaling in Foxd1-positive stromal cells promotes murine mephrogenesis via TGFβ signaling. Development 154(13):dev159947CrossRef
17.
go back to reference Phua YL, Chu JYS, Marrone AK, Bodnar AJ, Sims-Lucas S (2015) Renal stromal miRNAs are required for normal nephrogenesis and glomerular mesangial survival. Physiol Rep 3(10):e12537PubMedPubMedCentralCrossRef Phua YL, Chu JYS, Marrone AK, Bodnar AJ, Sims-Lucas S (2015) Renal stromal miRNAs are required for normal nephrogenesis and glomerular mesangial survival. Physiol Rep 3(10):e12537PubMedPubMedCentralCrossRef
18.
go back to reference Minuth WW, Denk L (2014) Structural links between the renal stem/progenitor cell niche and the organ capsule. Histochem Cell Biol 141(5):459–471PubMedCrossRef Minuth WW, Denk L (2014) Structural links between the renal stem/progenitor cell niche and the organ capsule. Histochem Cell Biol 141(5):459–471PubMedCrossRef
19.
go back to reference Minuth WW (2020) Shaping of the nephron - a complex, vulnerable, and pooely explored backdrop for noxae impairing nephrogenesis in the fetal human kidney. Mol Cell Pediatr 7(1):2PubMedPubMedCentralCrossRef Minuth WW (2020) Shaping of the nephron - a complex, vulnerable, and pooely explored backdrop for noxae impairing nephrogenesis in the fetal human kidney. Mol Cell Pediatr 7(1):2PubMedPubMedCentralCrossRef
20.
go back to reference Minuth WW (2021) Microanatomy of the developing nephron in the fetal human kidney during late gestation. Ann Anat 236:151705PubMedCrossRef Minuth WW (2021) Microanatomy of the developing nephron in the fetal human kidney during late gestation. Ann Anat 236:151705PubMedCrossRef
21.
go back to reference Levinson RS, Batourina E, Choi C, Vorontchikhina M, Kitajewki J, Mendelsohn CL (2005) Foxd1 - dependent signals control cellularity in the renal capsule, a structure required for normal renal development. Development 132(3):529–539PubMedCrossRef Levinson RS, Batourina E, Choi C, Vorontchikhina M, Kitajewki J, Mendelsohn CL (2005) Foxd1 - dependent signals control cellularity in the renal capsule, a structure required for normal renal development. Development 132(3):529–539PubMedCrossRef
22.
go back to reference Fleischmajer R, Jacobs L, Perlish JS, Katchen B, Schwartz E, Timpl R (1992) Immunochemical analysis of human kidney reticulin. Am J Pathol 140(5):1225–1235PubMedPubMedCentral Fleischmajer R, Jacobs L, Perlish JS, Katchen B, Schwartz E, Timpl R (1992) Immunochemical analysis of human kidney reticulin. Am J Pathol 140(5):1225–1235PubMedPubMedCentral
23.
go back to reference Lipp SN, Jacobson KR, Hains DS, Schwarderer AL, Calve S (2021) 3D mapping reveals a complex and transient interstitial matrix during murine renal development. J Am Soc Nephrol 32(7):1649–1665PubMedCentralCrossRef Lipp SN, Jacobson KR, Hains DS, Schwarderer AL, Calve S (2021) 3D mapping reveals a complex and transient interstitial matrix during murine renal development. J Am Soc Nephrol 32(7):1649–1665PubMedCentralCrossRef
24.
go back to reference Weiss AC, Rivera-Reyes R, Englert C, Kispert A (2020) Expansion of the capsular stroma, ureteric branching defects and cryptorchism in mice with Wilms tumor 1 gene deletion in the stromal compartment of the developing kidney. J Pathol 252:290–303PubMedCrossRef Weiss AC, Rivera-Reyes R, Englert C, Kispert A (2020) Expansion of the capsular stroma, ureteric branching defects and cryptorchism in mice with Wilms tumor 1 gene deletion in the stromal compartment of the developing kidney. J Pathol 252:290–303PubMedCrossRef
26.
27.
go back to reference Gerosa C, Fanni D, Faa A, Van Eyken P, Ravarino A, Fanos V, Faa G (2017) Low vascularization of the fetal kidney suggests a mojor role for hypoxia in human nephrogenesis. Int Urol Nephrol 49(9):1621–1625PubMedCrossRef Gerosa C, Fanni D, Faa A, Van Eyken P, Ravarino A, Fanos V, Faa G (2017) Low vascularization of the fetal kidney suggests a mojor role for hypoxia in human nephrogenesis. Int Urol Nephrol 49(9):1621–1625PubMedCrossRef
29.
go back to reference Kobayashi K (1978) Fine structure of the mammalian renal capsule: the atypical smooth muscle cell and its functional meaning. Cell Tissue Res 195(3):381–394PubMedCrossRef Kobayashi K (1978) Fine structure of the mammalian renal capsule: the atypical smooth muscle cell and its functional meaning. Cell Tissue Res 195(3):381–394PubMedCrossRef
31.
go back to reference England A, Chaney CP, Das A, Patel M, Malewska A, Armendariz D, Hon GC, Strand DW, Drake KA, Carroll TJ (2020) Identification and characterization of cellular heterogeneity within the developing renal interstitium. Development 147(15):dev90108 England A, Chaney CP, Das A, Patel M, Malewska A, Armendariz D, Hon GC, Strand DW, Drake KA, Carroll TJ (2020) Identification and characterization of cellular heterogeneity within the developing renal interstitium. Development 147(15):dev90108
32.
go back to reference Barwinska D, El-Achkar TM, Ferreira RM, Syed F, Cheng YH, Winfree S, Ferkowicz MJ, Hato T, Collins KS, Dunn KW, Kelly KJ, Sutton TA, Rovin BH, Parikh SV, Philipps CL, Dagher PC, Eadon MT (2012) Molecular characterization of the human kidney interstitium in health and disease. Sci Adv 7(7):eabd3359CrossRef Barwinska D, El-Achkar TM, Ferreira RM, Syed F, Cheng YH, Winfree S, Ferkowicz MJ, Hato T, Collins KS, Dunn KW, Kelly KJ, Sutton TA, Rovin BH, Parikh SV, Philipps CL, Dagher PC, Eadon MT (2012) Molecular characterization of the human kidney interstitium in health and disease. Sci Adv 7(7):eabd3359CrossRef
33.
go back to reference Minuth WW (2018) Reading first coordinates from the nephrogenic zone in human fetal kidney. Nephron 138(2):137–146PubMedCrossRef Minuth WW (2018) Reading first coordinates from the nephrogenic zone in human fetal kidney. Nephron 138(2):137–146PubMedCrossRef
34.
go back to reference O’Brien LL, Combes AN, Short KM, Lindström NO, Whitney PH, Cullen-McEven LA, Ju A, Abdelhalim A, Michos O, Bertram JF, Smyth IA, Little MH, McMahon AP (2018) Wnt11 directs nephron progenitor polarity and motile behavior ultimately determining nephron endowment. Elife 7:e40392PubMedPubMedCentralCrossRef O’Brien LL, Combes AN, Short KM, Lindström NO, Whitney PH, Cullen-McEven LA, Ju A, Abdelhalim A, Michos O, Bertram JF, Smyth IA, Little MH, McMahon AP (2018) Wnt11 directs nephron progenitor polarity and motile behavior ultimately determining nephron endowment. Elife 7:e40392PubMedPubMedCentralCrossRef
35.
go back to reference Fetting JL, Guay JA, Karolak MJ, Iozzo RV, Adams C, Maridas DE, Brown AC, Oxburgh L (2014) FOXD1 promotes nephron progenitor differentiation by repressing decorin in the embryonic kidney. Development 141(1):17–27PubMedPubMedCentralCrossRef Fetting JL, Guay JA, Karolak MJ, Iozzo RV, Adams C, Maridas DE, Brown AC, Oxburgh L (2014) FOXD1 promotes nephron progenitor differentiation by repressing decorin in the embryonic kidney. Development 141(1):17–27PubMedPubMedCentralCrossRef
36.
go back to reference Schumacher K, Strehl R, De Vries U, Groene HJ, Minuth WW (2002) SBA-positive fibers between the CD ampulla, mesenchyme and renal capsule. J Am Soc Nephrol 13:2446–2453PubMedCrossRef Schumacher K, Strehl R, De Vries U, Groene HJ, Minuth WW (2002) SBA-positive fibers between the CD ampulla, mesenchyme and renal capsule. J Am Soc Nephrol 13:2446–2453PubMedCrossRef
37.
go back to reference Schumacher K, Klar J, Wagner C, Minuth WW (2005) Temporal-spatial co-localisation of tissue transglutaminase (Tgase 2) and matrix metalloproteinase-9 (MMP-9) with SBA-positive microfibers in the embryonic kidney cortex. Cell Tissue Res 319:491–500PubMedCrossRef Schumacher K, Klar J, Wagner C, Minuth WW (2005) Temporal-spatial co-localisation of tissue transglutaminase (Tgase 2) and matrix metalloproteinase-9 (MMP-9) with SBA-positive microfibers in the embryonic kidney cortex. Cell Tissue Res 319:491–500PubMedCrossRef
38.
go back to reference Strehl R, Kloth S, Aigner J, Steiner P, Minuth WW (1997) PCDAmp1, a new antigen at the interface of the embryonic collecting duct epithelium and the nephrogenic mesenchyme. Kidney Int 52(6):1469–1477PubMedCrossRef Strehl R, Kloth S, Aigner J, Steiner P, Minuth WW (1997) PCDAmp1, a new antigen at the interface of the embryonic collecting duct epithelium and the nephrogenic mesenchyme. Kidney Int 52(6):1469–1477PubMedCrossRef
39.
go back to reference Strehl R, Trautner V, Kloth S, Minuth WW (1999) Existence of a dense reticular meshwork surrounding the nephron inducer in neonatal rabbit kidney. Cell Tissue Res 298(3):539–548PubMedCrossRef Strehl R, Trautner V, Kloth S, Minuth WW (1999) Existence of a dense reticular meshwork surrounding the nephron inducer in neonatal rabbit kidney. Cell Tissue Res 298(3):539–548PubMedCrossRef
40.
go back to reference Strehl R, Minuth WW (2001) Partial identification of the mab (CD) Amp1 antigen at the epithelial-mesenchymal interface in the developing kidney. Histochem Cell Biol 116(5):389–396PubMedCrossRef Strehl R, Minuth WW (2001) Partial identification of the mab (CD) Amp1 antigen at the epithelial-mesenchymal interface in the developing kidney. Histochem Cell Biol 116(5):389–396PubMedCrossRef
41.
go back to reference Mounier F, Foidart JM, Gubler MC (1986) Distribution of extracellular matrix glycoproteins during normal development of human kidney An immunohistochemical study. Lab Invest 54(4):394–401PubMed Mounier F, Foidart JM, Gubler MC (1986) Distribution of extracellular matrix glycoproteins during normal development of human kidney An immunohistochemical study. Lab Invest 54(4):394–401PubMed
42.
go back to reference Minuth WW, Denk L (2012) Cell projections and extracellular matrix cross the interstitial interface within the renal stem/progenitor cell niche: accidental, structural or functional cues? Nephron Exp Nephrol 122(3):131–140PubMed Minuth WW, Denk L (2012) Cell projections and extracellular matrix cross the interstitial interface within the renal stem/progenitor cell niche: accidental, structural or functional cues? Nephron Exp Nephrol 122(3):131–140PubMed
43.
go back to reference Minuth WW, Denk L (2013) The interstital interface within the renal stem/progenitor cell niche exhibits an unique microheterogeneous composition. Int J Mol Sci 14(7):13657–13669PubMedPubMedCentralCrossRef Minuth WW, Denk L (2013) The interstital interface within the renal stem/progenitor cell niche exhibits an unique microheterogeneous composition. Int J Mol Sci 14(7):13657–13669PubMedPubMedCentralCrossRef
44.
go back to reference Lindström NO, De Sena BG, Tran T, Ransick A, Suh G, Guo J, Kim AD, Parvez RK, Ruffins SW, Rutledge EA, Thornton ME, Grubbs B, McMahon JA, Smith AD, McMahon AP (2018) Progressive recruitment of mesenchymal progenitor cells reveals a time-dependent process of cell fate acquisition in mouse and human nephrogenesis. Dev Cell 45(5):651–660PubMedPubMedCentralCrossRef Lindström NO, De Sena BG, Tran T, Ransick A, Suh G, Guo J, Kim AD, Parvez RK, Ruffins SW, Rutledge EA, Thornton ME, Grubbs B, McMahon JA, Smith AD, McMahon AP (2018) Progressive recruitment of mesenchymal progenitor cells reveals a time-dependent process of cell fate acquisition in mouse and human nephrogenesis. Dev Cell 45(5):651–660PubMedPubMedCentralCrossRef
45.
go back to reference Kao RM, Vasilyev A, Miyawaki A, Drummond IA, McMahon AP (2012) Invasion of distal nephron precursors associates with tubular interconnection during nephrogenesis. J Am Soc Nephrol 23(10):1682–1690PubMedPubMedCentralCrossRef Kao RM, Vasilyev A, Miyawaki A, Drummond IA, McMahon AP (2012) Invasion of distal nephron precursors associates with tubular interconnection during nephrogenesis. J Am Soc Nephrol 23(10):1682–1690PubMedPubMedCentralCrossRef
46.
go back to reference Zhang P, Gu L, Cong J, Zhang J, Thomsen JS, Andreasen A, Chang SJ, Deng SQ, Xing J, Zhai XY (2019) Morphology of the initial nephron-collecting duct connection in mice using computerized 3D tracing and electron microscopy. Biochem Biophys Res Commun 509(1):114–118PubMedCrossRef Zhang P, Gu L, Cong J, Zhang J, Thomsen JS, Andreasen A, Chang SJ, Deng SQ, Xing J, Zhai XY (2019) Morphology of the initial nephron-collecting duct connection in mice using computerized 3D tracing and electron microscopy. Biochem Biophys Res Commun 509(1):114–118PubMedCrossRef
47.
go back to reference Sarkany B, Kovacs G (2021) Connecting tubules develop from the tip of the ureteric bud in the human kidney. Histochem Cell Biol 156(6):555–560PubMed Sarkany B, Kovacs G (2021) Connecting tubules develop from the tip of the ureteric bud in the human kidney. Histochem Cell Biol 156(6):555–560PubMed
48.
go back to reference Miess C, Glashauser A, Denk L, deVries U, Minuth WW (2010) The interface between generating renal tubules and a polyester fleece in comparison to the interstitium of the developing kidney. Ann Biomed Eng 38(6):2197–2209PubMedCrossRef Miess C, Glashauser A, Denk L, deVries U, Minuth WW (2010) The interface between generating renal tubules and a polyester fleece in comparison to the interstitium of the developing kidney. Ann Biomed Eng 38(6):2197–2209PubMedCrossRef
49.
go back to reference Schumacher A, Rookmaaker MB, Joles JA, Kramann R, Nguyen TQ, van Griensven M, LaPointe VLS (2021) Defining the variety of cell types in developing and adult human kidneys by single-cell RNA sequencing. Regen Med 6:45 Schumacher A, Rookmaaker MB, Joles JA, Kramann R, Nguyen TQ, van Griensven M, LaPointe VLS (2021) Defining the variety of cell types in developing and adult human kidneys by single-cell RNA sequencing. Regen Med 6:45
50.
go back to reference Wilson SB, Little MH (2021) The origin and role of the renal stroma. Development 148(19):dev99886CrossRef Wilson SB, Little MH (2021) The origin and role of the renal stroma. Development 148(19):dev99886CrossRef
Metadata
Title
The interstitium at the developing nephron in the fetal kidney during advanced pregnancy — a microanatomical inventory
Author
Will W. Minuth
Publication date
01-12-2022
Publisher
Springer International Publishing
Published in
Molecular and Cellular Pediatrics / Issue 1/2022
Electronic ISSN: 2194-7791
DOI
https://doi.org/10.1186/s40348-022-00149-9

Other articles of this Issue 1/2022

Molecular and Cellular Pediatrics 1/2022 Go to the issue