Development of the Urinary Tract in Fetal Rats: A Micro-CT Study

Stephanie Wille; Nicole Peukert; Rainer Haak; Jan Riedel; Steffi Mayer; Dietrich Kluth; Martin Lacher; Jan-Hendrik Gosemann; Moritz Markel

doi:10.1055/s-0042-1758681

European Journal of Pediatric Surgery, Table of Contents

Eur J Pediatr Surg 2023; 33(01): 053-060
DOI: 10.1055/s-0042-1758681

Original Article

Development of the Urinary Tract in Fetal Rats: A Micro-CT Study

Authors

Stephanie Wille

¹Department of Pediatric Surgery, University of Leipzig, Leipzig, Germany

²Department of Interdisciplinary Medical Intensive Care, University of Leipzig, Leipzig, Germany
Nicole Peukert

¹Department of Pediatric Surgery, University of Leipzig, Leipzig, Germany
Rainer Haak

³Department of Cariology, Endodontology, and Periodontology, University of Leipzig, Leipzig, Germany
Jan Riedel

¹Department of Pediatric Surgery, University of Leipzig, Leipzig, Germany
Steffi Mayer

¹Department of Pediatric Surgery, University of Leipzig, Leipzig, Germany
Dietrich Kluth

¹Department of Pediatric Surgery, University of Leipzig, Leipzig, Germany
Martin Lacher

¹Department of Pediatric Surgery, University of Leipzig, Leipzig, Germany
Jan-Hendrik Gosemann^*

¹Department of Pediatric Surgery, University of Leipzig, Leipzig, Germany
Moritz Markel^*

¹Department of Pediatric Surgery, University of Leipzig, Leipzig, Germany

Abstract

Introduction Micro-computed tomography (micro-CT) is an established tool to study fetal development in rodents. This study aimed to use micro-CT imaging to visualize the development of the urinary tract in fetal rats.

Materials and Methods Fetal rats from embryonic day (ED) 15, ED17, ED19, ED21, and N0 (newborn) (n = 6 per group; 3 males) were fixed and desiccated using the “critical point” technique. We utilized the micro-CT system (SkyScan) and analyzed the resulting scans with CTAn, DataViewer, and ImageJ to visualize the morphology and quantify the volumes of kidney, bladder, adrenal gland, as well as length of the ureter.

Results High-resolution micro-CT showed continuous growth of both kidneys from ED15 to N0, with the highest increase between ED19 and ED21. The length of the ureter increased from ED15 to ED21 and remained stable until birth. The volume of the bladder steadily increased from ED15 to N0.

In females, a statistically higher volume of the adrenal gland on ED21 was observed, whereas no sex-specific differences were seen for kidney, ureter, and bladder development.

Conclusion Micro-CT depicts an excellent tool to study urinary tract development in the fetal and neonatal rat. It enables the metric quantification of longitudinal anatomic changes in high definition without previous destructive tissue preparation. The present study revealed sex-specific differences of the adrenal gland development and provides comprehensive data for the understanding of fetal urinary tract development, inspiring future research on congenital urological malformations.

Keywords

micro-CT - kidney development - adrenal gland development - ureter development - bladder development

Full Text

References

References
1 Becker A, Baum M. Obstructive uropathy. Early Hum Dev 2006; 82 (01) 15-22
2 Woolf AS, Thiruchelvam N. Congenital obstructive uropathy: its origin and contribution to end-stage renal disease in children. Adv Ren Replace Ther 2001; 8 (03) 157-163
3 Farrugia MK, Woolf AS. Congenital urinary bladder outlet obstruction. Fetal Matern Med Rev 2010; 21 (01) 55-73
4 Podevin G, Mandelbrot L, Vuillard E, Oury JF, Aigrain Y. Outcome of urological abnormalities prenatally diagnosed by ultrasound. Fetal Diagn Ther 1996; 11 (03) 181-190
5 Hinchliffe SA, Sargent PH, Howard CV, Chan YF, van Velzen D. Human intrauterine renal growth expressed in absolute number of glomeruli assessed by the disector method and Cavalieri principle. Lab Invest 1991; 64 (06) 777-784
6 Kreidberg JA. Podocyte differentiation and glomerulogenesis. J Am Soc Nephrol 2003; 14 (03) 806-814
7 Erb C. Embryology and teratology. The Laboratory Rat 2006; 817-846
8 Hristić M, Kalafatić D, Plećas B, Manojlović M. The influence of prolonged dexamethasone treatment of pregnant rats on the perinatal development of the adrenal gland of their offspring. J Exp Zool 1997; 279 (01) 54-61
9 Josimovich JB, Ladman AJ, Deane HW. A histophysiological study of the developing adrenal cortex of the rat during fetal and early postnatal stages. Endocrinology 1954; 54 (06) 627-639
10 Hebel R, Stromberg MW. Anatomy of the Laboratory Rat. Vol. VIII. Baltimore, MD: The Williams and Wilkins Company; 1976
11 Bertram JF, Young RJ, Spencer K, Gordon I. Quantitative analysis of the developing rat kidney: absolute and relative volumes and growth curves. Anat Rec 2000; 258: 128-135
12 Mirhish SM, Khalaf NH. Histomorphological Study of Mesonephric Kidney Development in Prenatal Stages of Rats (Rattus Norvegicus Albinus). Diyala Agricultural Sciences Journal 2016; 8 (01) 1-12
13 Magalhães MM, Breda JR, Magalhães MC. Ultrastructural Studies On the Prenatal Development of the Rat Adrenal Cortex. Journal of Ultrastructure Research 1978; 64 (02) 115-123
14 Ezuruike U, Blenkinsop A, Pansari A, Abduljalil K. Quantification of fetal renal function using fetal urine production rate and its reflection on the amniotic and fetal creatinine levels during pregnancy. Front Pediatr 2022; 10: 841495
15 van Vuuren SH, Damen-Elias HAM, Stigter RH. et al. Size and volume charts of fetal kidney, renal pelvis and adrenal gland. Ultrasound Obstet Gynecol 2012; 40 (06) 659-664
16 Chitty LS, Altman DG. Charts of fetal size: kidney and renal pelvis measurements. Prenat Diagn 2003; 23 (11) 891-897
17 Blake J, Rosenblum ND. Renal branching morphogenesis: morphogenetic and signaling mechanisms. Semin Cell Dev Biol 2014; 36: 2-12
18 Costantini F. Genetic controls and cellular behaviors in branching morphogenesis of the renal collecting system. Wiley Interdiscip Rev Dev Biol 2012; 1 (05) 693-713
19 Shanmugam S, Llorens-Cortes C, Clauser E, Corvol P, Gasc JM. Expression of angiotensin II AT2 receptor mRNA during development of rat kidney and adrenal gland. Am J Physiol 1995; 268 (5 Pt 2): F922-F930
20 Rasouly HM, Lu W. Lower urinary tract development and disease. Wiley Interdiscip Rev Syst Biol Med 2013; 5 (03) 307-342
21 Ginzel M, Martynov I, Haak R, Lacher M, Kluth D. Midgut development in rat embryos using microcomputed tomography. Commun Biol 2021; 4 (01) 190
22 Metscher BD. MicroCT for comparative morphology: simple staining methods allow high-contrast 3D imaging of diverse non-mineralized animal tissues. BMC Physiol 2009; 9 (01) 11
23 Brosig S, Peukert N, Metzger R. et al. X-ray micro-computed-tomography in pediatric surgery: a new tool for studying embryos. Pediatr Surg Int 2018; 34 (03) 297-305
24 Markel M, Ginzel M, Peukert N. et al. High resolution three-dimensional imaging and measurement of lung, heart, liver, and diaphragmatic development in the fetal rat based on micro-computed tomography (micro-CT). J Anat 2020; 238 (04) 1042-1054
25 Alcaraz A, Vinaixa F, Tejedo-Mateu A. et al. Obstruction and recanalization of the ureter during embryonic development. J Urol 1991; 145 (02) 410-416
26 Yu OH, Murawski IJ, Myburgh DB, Gupta IR. Overexpression of RET leads to vesicoureteric reflux in mice. Am J Physiol Renal Physiol 2004; 287 (06) F1123-F1130
27 Radmayr C, Schwentner C, Lunacek A, Karatzas A, Oswald J. Embryology and anatomy of the vesicoureteric junction with special reference to the etiology of vesicoureteral reflux. Ther Adv Urol 2009; 1 (05) 243-250
28 Cullen-McEwen LA, Fricout G, Harper IS, Jeulin D, Bertram JF. Quantitation of 3D ureteric branching morphogenesis in cultured embryonic mouse kidney. Int J Dev Biol 2002; 46 (08) 1049-1055
29 Baskin LS, Hayward SW, Sutherland RA. et al. Mesenchymal-epithelial interactions in the bladder. World J Urol 1996; 14: 301-309
30 Baker LA, Gomez RA. Embryonic development of the ureter and bladder: acquisition of smooth muscle. J Urol 1998; 160 (02) 545-550
31 Padbury JF, Hobel CJ, Lam RW, Fisher DA. Sex differences in lung and adrenal neurosympathetic development in rabbits. Am J Obstet Gynecol 1981; 141 (02) 199-204

Supplementary Material

Supplementary Material (PDF)