Urinary Bladder Development

Embryology - 30 Oct 2020        Expand to Translate
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Introduction

Adult male and female urinary bladder

Interior of the urinary bladder

The paired adult kidneys filter blood, reabsorb water, have endocrine functions and excrete waste. The waste in the form of urine for excretion, collects initially in the renal pelvis and flows through the ureters to the urinary bladder. The wall of the urinary bladder is composed of layers of smooth muscle and in the male has close anatomical relationship with the prostate gland. (More? prostate)

Abnormalities in renal development can lead to ureter obstruction and interfere with flow of urine to the bladder during the fetal period.

The common name for the urinary bladder is simply the "bladder".

Historic Bladder: 1912 Cloaca, Bladder, Urethra, and Urogenital Sinus | 1921 Urinary Bladder

Some Recent Findings

Mouse cloacal septation

Foxa1 and Foxa2 orchestrate development of the urethral tube and division of the embryonic cloaca through an autoregulatory loop with Shh "Congenital anomalies of external genitalia affect approximately 1 in 125 live male births. Development of the genital tubercle, the precursor of the penis and clitoris, is regulated by the urethral plate epithelium, an endodermal signaling center. Signaling activity of the urethral plate is mediated by Sonic hedgehog (SHH), which coordinates outgrowth and patterning of the genital tubercle by controlling cell cycle kinetics and expression of downstream genes. The mechanisms that govern Shh transcription in urethral plate cells are largely unknown. Here we show that deletion of Foxa1 and Foxa2 results in persistent cloaca, an incomplete separation of urinary, genital, and anorectal tracts, and severe hypospadias, a failure of urethral tubulogenesis. Loss of Foxa2 and only one copy of Foxa1 results in urethral fistula, an additional opening of the penile urethra. Foxa1/a2 participate in an autoregulatory feedback loop with Shh, in which FOXA1 and FOXA2 positively regulate transcription of Shh in the urethra, and SHH feeds back to negatively regulate Foxa1 and Foxa2 expression. These findings reveal novel roles for Foxa genes in development of the urethral tube and in division of the embryonic cloaca." Morphology of the fetal bladder during the second trimester: Comparing genders "Forty bladders, which were obtained from 40 human fetuses (20 males and 20 females) ranging in age from 13 to 23 weeks post-conception (WPC), were studied. The fetuses weighed between 60 and 490 g, and had crown-rump lengths between 9.5 and 20.4 cm. No elastic system fibers were observed in any bladders. ...The histological analysis of the smooth muscle, collagen, nerves and connective tissue of the developing bladders revealed that there are no gender differences during weeks 13-23 of gestation." Spatio-temporal distribution of Smads and role of Smads/TGF-β/BMP-4 in the regulation of mouse bladder organogenesis "Although Shh, TGF-β and BMP-4 regulate radial patterning of the bladder mesenchyme and smooth muscle differentiation, it is not known what transcription factors, local environmental cues or signaling cascades mediate bladder smooth muscle differentiation. ...Based on the Smad expression patterns, we suggest that individual or combinations of Smads may be necessary during mouse bladder organogenesis and may be critical mediators for bladder smooth muscle differentiation." TGF-beta

More recent papers

This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on this list based upon the date of the actual page viewing. References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability. More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Bladder Embryology | Bladder Development | Ureter Development | Urethra Development | Trigone Development | Detrusor Development

Older papers

These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table. See also the Discussion Page for other references listed by year and References on this current page. Endodermal origin of bladder trigone inferred from mesenchymal-epithelial interaction "In the classic view of bladder development the trigone originates from the mesoderm derived wolffian ducts while the remainder of the bladder originates from the endoderm derived urogenital sinus. Recent molecular developmental studies have questioned the veracity of this received wisdom, suggesting an endodermal origin for the trigone. To shed further light on this issue we observed mesenchymal-epithelial interactions between trigone epithelium and fetal urogenital sinus mesenchyma to infer the trigonal germ layer of origin."

Textbook References

• The Developing Human: Clinically Oriented Embryology (8th Edition) by Keith L. Moore and T.V.N Persaud - Moore & Persaud Chapter 13 p303-346
• Larsen’s Human Embryology by GC. Schoenwolf, SB. Bleyl, PR. Brauer and PH. Francis-West - Chapter 10 p261-306

Movies

‎‎Renal Overview Page | Play

‎‎Nephron Page | Play

‎‎Urogenital Septum Page | Play

‎‎Trigone Page | Play

‎‎GIT Stage 13 Page | Play

‎‎Urogenital Page | Play

‎‎Renal Vascular Page | Play

Renal System Development | All Renal Cartoons

Cloaca

Animation - Endoderm forming the cloaca and the primitive urinary bladder continuous with the allantois.

• hindgut region ending at the cloacal membrane
• divided (ventro-dorsally) by the urogenital septum
  • ventral - common urogenital sinus
  • dorsal - rectum

Common Urogenital Sinus

• superior end continuous with allantois
• common urogenital sinus and mesonephric duct fuse (connect)
• differentiates to form the bladder
• inferior end forms urethra
  • this will be different in male and female development

Urogenital Septum

‎‎Urogenital Septum

Page | Play

Links: cloaca

Urinary Bladder Development

Adult bladder

• early origins of the bladder at the superior end of the common urogenital sinus
• open inferiorly to the cloaca and superiorly to the allantois
• Septation of the claoca - divides the anterior region to the primordial bladder component from the posterior rectal component.
• associated ureters and urethra

Dorsal view of developing bladder

‎‎Trigone

Page | Play

• Ultrasound measurement of the bladder size can be used as a diagnostic tool for developmental abnormalities.

Bladder Epithelium

The embryonic epithelium remains unaltered for a long time varying from columnar to low cubical. The mulitlayered epithelium first begins in the early fetus (week 10, 50 mm head-foot length) in the caudal portion. The transitional epithelium appears in the fetus of 60 mm head-foot-length.

• one-layered epithelium - at the apex.
• two-layered epithelium - dorsal and ventral surface (thicker on dorsal).
• many-layered epithelium - at the fundus.

Detrusor Muscle

• The adult detrusor muscle consists of three layers of smooth (involuntary) muscle fibres.
  • external layer - fibres arranged longitudinally
  • middle layer - fibres arranged circularly
  • internal layer - fibres arranged longitudinally

Links: smooth muscle

Trigone Development

‎‎Trigone

Page | Play

Week 8

The Carnegie stage 22 human male embryo is 27mm (CRL) in size and approximately equal to day 54 - 56 of development. These images have been selected to show some key features of late embryo development.

G5 urogenital	G6 urogenital	G7 urogenital	unlabeled	labeled

Links: Stage 13 - Renal | Stage 22 - Renal | Carnegie stage 13 | Carnegie stage 22

Fetal Urinary Bladder

Fetal Development - 10 Weeks - Early female fetal bladder development. Anatomically lying behind the pubic symphysis and in front of the developing uterus. Surrounded by the developing detrusor muscle and the superior end extending towards the ventral body wall herniation.

midline section	medial section

Links: Fetal Development - 10 Weeks

MRI appearance of normal fetal kidney. Sagittal T2- SSFSE of a fetal abdomen at GA 25 week. Adequate volume of the amniotic fluid and the developing lungs indicate good renal function. two arrowheads - note the size and the signal appearance of the normal kidney. white arrow - the fluid-filled urinary bladder black arrow - the developing lung. Note that the urinary bladder can occupy a considerable portion of the abdomen as a normal finding. Links: Magnetic Resonance Imaging

Ureter Development

Embryonic ureter at time of cloaca septation

• The adult ureter is a thick-walled muscular tube, 25 - 30 cm in length, running from the kidney to the urinary bladder.
• Anatomically can be described in two parts the abdominal part (pars abdominalis) and pelvic part (pars pelvina).
• The ureter is composed of three layers: outer fibrous layer (tunica adventitia), muscular layer (tunica muscularis) and mucous layer (tunica mucosa).
• The muscular layer can also be subdivided into 3 fibre layers: an external longitudinal, a middle circular, and an internal longitudinal.

Historic

Robert Meyer (1864 – 1947)

The "Weigert-Meyer law" is a rule concerning the anatomical relationship of the two ureters, named after the pathologist Carl Weigert in conjunction with the embryologist Robert Meyer

PubMed: Ureter Development

Urethra Development

• Contrasting mechanisms of penile urethral formation in mouse and human "This paper addresses the developmental mechanisms of formation of the mouse and human penile urethra and the possibility that two disparate mechanisms are at play. It has been suggested that the entire penile urethra of the mouse forms via direct canalization of the endodermal urethral plate. While this mechanism surely accounts for development of the proximal portion of the mouse penile urethra, we suggest that the distal portion of the mouse penile urethra forms via a series of epithelial fusion events. Through review of the recent literature in combination with new data, it is unlikely that the entire mouse urethra is formed from the endodermal urethral plate due in part to the fact that from E14 onward the urethral plate is not present in the distal aspect of the genital tubercle. Formation of the distal portion of the mouse urethra receives substantial contribution from the preputial swellings that form the preputial-urethral groove and subsequently the preputial-urethral canal, the later of which is subdivided by a fusion event to form the distal portion of the mouse penile urethra. Examination of human penile development also reveals comparable dual morphogenetic mechanisms. However, in the case of human, direct canalization of the urethral plate occurs in the glans, while fusion events are involved in formation of the urethra within the penile shaft, a pattern exactly opposite to that of the mouse. The highest incidence of hypospadias in humans occurs at the junction of these two different developmental mechanisms. The relevance of the mouse as a model of human hypospadias is discussed."

Historic Urethra: 1912 Cloaca, Bladder, Urethra, and Urogenital Sinus

Search PubMed: Urethra Development

Newborn Urinary Bladder

The Newborn Male Bladder	The Newborn Female Bladder

Bladder Histology

Urinary bladder histology

Can be described anatomically by its 4 layers from outside inward:

• Serous - the superior or abdominal surfaces and the lateral" surfaces of the bladder are covered by visceral peritoneum, the serous membrane (serosa) of the abdominal cavity, consisting of mesthelium and elastic fibrous connective tissue.
• Muscular - the detrusor muscle is the muscle of the urinary bladder wall.
• Submucosa - connects the muscular layer with the mucous layer.
• Mucosa - (mucus layer) a transitional epithelium layer formed into folds (rugae).

Urinary bladder wall drawing

Animal Models

Mouse bladder development E12.5-E16.5

Abnormalities

Duplicated Bladder

Urinary bladder duplication is an extremely rare abnormality. This MRI of a male newborn infant shows the duplicated bladder and also duplicated external genitalia (phallus). red arrow - collapsed right bladder blue arrow - distended left bladder orange arrow - midline septum yellow arrow - right phallus green arrow - left phallus Links: Magnetic Resonance Imaging

Urorectal Septum Malformation

• thought to be a deficiency in caudal mesoderm which in turn leads to the malformation of the urorectal septum and other structures in the pelvic region.
• Recent research has also identified the potential presence of a persistent urachus prior to septation of the cloaca (common urogenital sinus).

Bladder Exstrophy

Bladder_Exstrophy

{{ICD-11} LB31.3 Exstrophy of urinary bladder - Bladder exstrophy (or classic bladder exstrophy) is a congenital genitourinary malformation belonging to the spectrum of the exstrophy-epispadias complex and is characterized by an evaginated bladder plate, epispadias and an anterior defect of the pelvis, pelvic floor and abdominal wall.

• developmental abnormality associated with bladder development.
• origins appear to occur not just by abnormal bladder development, but by a congenital malformation of the ventral wall of abdomen (between umbilicus and pubic symphysis).
• There may also be other anomalies associated with failure of closure of abdominal wall and bladder (epispadias, pubic bone anomalies).

Neonatal Bladder Exstrophy

Male	Female	=	alt=male bladder exstrophy|300px	alt=female bladder exstrophy|300px

Absent Bladder

Absent or small bladder can be associated with renal agenesis.

Ureter and Urethra

• Ureter - Duplex Ureter
• Urethra- Urethral Obstruction and Hypospadias

Prune Belly Syndrome

• 
• 
• 

  Prune_belly

• lower urinary tract obstruction
• mainly male
• fetal urinary system ruptures leading to collapse and "prune belly" appearance.

Horseshoe Kidney

Horseshoe kidney

• fusion of the lower poles of the kidney.
• During migration from the sacral region the two metanephric blastemas can come into contact, mainly at the lower pole.
• The ureters pass in front of the zone of fusion of the kidneys.
• The kidneys and ureters usually function adequately but there is an increased incidence of upper urinary tract obstruction or infection.
• Some horseshoe variations have been described as having associated ureter abnormalities including duplications.

References

Reviews

Shen J, Overland M, Sinclair A, Cao M, Yue X, Cunha G & Baskin L. (2016). Complex epithelial remodeling underlie the fusion event in early fetal development of the human penile urethra. Differentiation , 92, 169-182. PMID: 27397682 DOI.

Shapiro E. (2009). Clinical implications of genitourinary embryology. Curr Opin Urol , 19, 427-33. PMID: 19461520 DOI.

Brenner-Anantharam A, Cebrian C, Guillaume R, Hurtado R, Sun TT & Herzlinger D. (2007). Tailbud-derived mesenchyme promotes urinary tract segmentation via BMP4 signaling. Development , 134, 1967-75. PMID: 17442697 DOI.

Costantini F. (2006). Renal branching morphogenesis: concepts, questions, and recent advances. Differentiation , 74, 402-21. PMID: 16916378 DOI.

Search Bookshelf bladder development | trigone development ureter development

Articles

Viana R, Batourina E, Huang H, Dressler GR, Kobayashi A, Behringer RR, Shapiro E, Hensle T, Lambert S & Mendelsohn C. (2007). The development of the bladder trigone, the center of the anti-reflux mechanism. Development , 134, 3763-9. PMID: 17881488 DOI.

Search PubMed

Search Pubmed: urinary bladder development | bladder development

Images

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  Endoderm cartoon

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  Fetal urogenital region most lateral right

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  Fetal urogenital region lateral right

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  Fetal urogenital region medial

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  Fetal urogenital region midline

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  Fetal kidney (10 weeks)

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  Bladder histology

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  Prune belly

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  Renal outflow obstruction

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  Bladder Exstrophy

Historic Images

Historic Disclaimer - information about historic embryology pages

Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

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  Stage 11 historic Atwell (1930)

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  Stage 11 historic Heuser (1930)

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  retroperitoneal

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  Fig. 1139 Adult Female Bladder

Bailey FR. and Miller AM. Text-Book of Embryology (1921) New York: William Wood and Co.

Text-Book of Embryology. Bailey, F.R. and Miller, A.M. (1921). New York: William Wood and Co. The Urinary Bladder

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  Cloaca and surrounding structures human embryo of 6.5 mm

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  Cloacal region human embryo

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  Caudal end human embryo of 11.5 mm

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  Caudal end human embryo of 25 mm

Keith A. Human Embryology and Morphology. (1902) London: Edward Arnold. The Uro-genital System

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  Fig. 99. A section of the male bladder and urethra at birth

Terms

• bladder exstrophy - A congenital malformation with bladder open to ventral wall of abdomen (between umbilicus and pubic symphysis) and may have other anomolies associated with failure of closure of abdominal wall and bladder (epispadias, pubic bone anomolies).
• hydronephrosis - (congenital hydronephrosis, Greek, hydro = water) A kidney abnormality due to partial or complete obstruction at the pelvi-ureteric junction. This leads to a grossly dilated renal pelvis causing extensive renal damage before birth.
• mesonephric duct - (= Wollfian duct) An early developing urogenital duct running the length of the embryo that will differentiate and form the male reproductive duct system. In females this duct degenerates (some remnants may remain associated in broad ligament).
• proteinuria - The abnormal presence of protein in the urine and an indicator of diesease including diabetic kidney disease (DKD, diabetic nephropathy).
• renal - (Latin, renes = kidney) Term used in relation to the kidney and associated structures (renal pelvis, renal artery)
• ureter - The two ureters are hollow tubes that link and carries urine from kidney to the bladder. The tubes have a muscular wall lined with transitional epithelium.
• urethra - The single muscular tube that links and carries urine from the bladder to the exterior. In humans, the urethral length differs between the sexes (male longer, female shorter).
• urinary - Term used to describe all components of the kidney system including the bladder, ureters and urethra.
• urine - Term used to describe the liquid waste produced by the kidney, stored in the bladder and excreted from teh body through the urethra.
• urorectal septum - (URS) The structure which develops to separate the cloaca (common urogenital sinus) into an anterior urinary part and a posterior rectal part.
• Wolffian duct - (= mesonephric duct, preferred terminology), runs from the mesonephros to cloaca, differentiates to form the male vas deferens and in the female regresses. Named after Caspar Friedrich Wolff (1733-1794), a German scientist and early embryology researcher and is said to have established the doctrine of germ layers. (More? Caspar Friedrich Wolff)

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Cite this page: Hill, M.A. (2020, October 30) Embryology Urinary Bladder Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Urinary_Bladder_Development

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© Dr Mark Hill 2020, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G