The Effect of Obstruction on the Developing Bladder

Peters, Craig A.; Vasavada, Sandip; Dator, Dante P.; Carr, Michael C.; Shapiro, Ellen; Lepor, Herbert; McConnell, John D.; Retik, Alan B.; Mandell, James

doi:10.1016/s0022-5347(17)36638-7

Cited by 117 publications

(52 citation statements)

References 19 publications

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“…Thirty days of BOO resulted in enhanced growth of the fetal bladder as assessed by whole bladder weight, protein, and DNA measurements, somewhat similar to the results of Peters and colleagues, 8 discussed above. Assessing PCNA protein expression, a surrogate marker of proliferation, we noted that experimental fetal BOO was associated with a significantly increased percentage of proliferating detrusor SMC versus sham controls, with no significant difference in the lamina propria or urothelial cells between the two groups.…”

Section: Boo Deregulates Proliferation and Apoptosis In The Developinsupporting

confidence: 83%

“…After BOO from 60 days through to term, bladder weight increased approximately fivefold versus sham controls. 8 As assessed by various morphometric analyses performed at term, detrusor muscle average cell volume was found to have increased, as had "total smooth muscle mass;" total bladder DNA increased approximately twofold but there was a significantly greater increase in protein. The authors concluded that the response to fetal BOO was mainly accounted for by hypertrophy, with a lesser contribution from hyperplasia; in a limited analysis after only 35 days obstruction, obstructed bladders were also heavier than controls.…”

Section: Known Effects Of Experimental Boo On the Fetal Bladdermentioning

confidence: 96%

“…However, probably because the urachus was not ligated, neither the bladder not the upper tracts were severely damaged. Peters and colleagues, 8,14,24 refined the model to include experimental urachal obstruction, a protocol which resulted in hydronephrosis and renal cystic changes. After BOO from 60 days through to term, bladder weight increased approximately fivefold versus sham controls.…”

Section: Known Effects Of Experimental Boo On the Fetal Bladdermentioning

confidence: 99%

“…5 Furthermore, this bladder dysfunction is implicated in postnatal loss of renal excretory function, a process which summates with congenital kidney damage. 2,6 Experimental models of fetal urinary tract obstruction have exploited the sheep as a model because ovine fetuses can be manipulated relatively early in gestation without major mortality [7][8][9][10] and by mid-gestation, ovine bladders receive 5 to 6 ml of urine each hour from the metanephroi. 11 Investigation of human fetal bladder development illustrates how the bladder thickens and has increased elastic fibers and decreased collagen deposition during maturation of the fetus.…”

mentioning

confidence: 99%

“…Therefore, investigators have combined fetal sheep urethral and urachal ligation to model bladder pathology which might reflect human diseases with congenital BOO. 8 -10 Peters et al 8 produced ovine BOO at 60 days gestation and sacrificed fetuses after 35 or 85 days; a marked growth response was found in obstructed bladders as assessed by increased bladder weight, DNA and protein content, and detrusor smooth muscle cell (SMC) size. Using a similar methodology, we reported that severe BOO 10 between 75 and 105 days gestation reduced bladder muscle contractility, compliance, and innervation; this model uses severe BOO to produce a experimental phenotype which resembles dysmorphic, massively dilated bladders reported in autopsy cases of severe human fetal PUV and PBS.…”

mentioning

confidence: 99%

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Urinary Outflow Obstruction Increases Apoptosis and Deregulates Bcl-2 and Bax Expression in the Fetal Ovine Bladder

Thiruchelvam

Nyírády

Peebles

et al. 2003

The American Journal of Pathology

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During organogenesis, net growth of tissues is determined by a balance between proliferation, hypertrophy, and apoptotic death. Human fetal bladder outflow obstruction is a major cause of end-stage renal failure in children and is associated with complex pathology in the kidney and lower urinary tract. Experimental manipulation of the fetal sheep urinary tract has proved informative in understanding the pathobiology of congenital obstructive uropathy. In this study we used an ovine model of fetal bladder outflow obstruction to examine effects on apoptotic cell death in the developing urinary bladder. While 30 days of obstruction in utero between 75 and 105 days gestation resulted in overall growth of the fetal bladder as assessed by weight, protein, and DNA measurements, we found that apoptosis, as assessed by in situ end-labeling, was up-regulated in fetal bladder detrusor muscle and lamina propria cells and that this was accompanied by a down-regulation of the anti-death protein Bcl-2 and an up-regulation of the pro-death protein Bax. Moreover, activated caspase-3, an effector of apoptotic death, was increased in obstructed bladders. This is the first study to define altered death in an experimental fetal model of bladder dysmorphogenesis. We speculate that enhanced apoptosis in detrusor smooth muscle cells is part of a remodeling response during compensatory hyperplasia and hypertrophy. Conversely, in the lamina propria, an imbalance between death and proliferation leads to a relative depletion of cells.

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Section: Boo Deregulates Proliferation and Apoptosis In The Developinsupporting

confidence: 83%

Section: Known Effects Of Experimental Boo On the Fetal Bladdermentioning

confidence: 96%

Section: Known Effects Of Experimental Boo On the Fetal Bladdermentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Urinary Outflow Obstruction Increases Apoptosis and Deregulates Bcl-2 and Bax Expression in the Fetal Ovine Bladder

Thiruchelvam

Nyírády

Peebles

et al. 2003

The American Journal of Pathology

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Compliance of the obstructed fetal rabbit bladder

et al. 1997

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Morphological, stereological, and biochemical analysis of the mini‐pig urinary bladder after chronic outflow obstruction and after recovery from obstruction

Nielsen

Andersen

Petersen

et al. 1995

Neurourology and Urodynamics

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Chronic partial bladder outlet obstruction was created in nine mini-pigs by implanting a 6-7 mm ring around the proximal urethra. After a median obstruction period of 63 days, the ring was removed and after a recovery period of median 60 days the animals were sacrificed. Changes in muscle and connective tissue were assessed by unbiased, modern morphometry and biochemical analysis. After obstruction the results were as follows: (1) a 6-fold increase in bladder weight, (2) a 2.5-fold increase in smooth muscle cell size, (3) a 3-fold increase in smooth muscle cell number, (4) unchanged proportions between muscle and connective tissue, (5) unchanged hydroxyproline concentrations, (6) an 8-fold increase in total collagen content, (7) an increase in the ratio of type I/III collagen, and (8) a 7-8-fold increase in total content of type I and III collagen. All changes were markedly, though incompletely, reversed after recovery, except smooth muscle cell number and the ratio of type I/III collagen.

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The Effect of Obstruction on the Developing Bladder

Cited by 117 publications

References 19 publications

Urinary Outflow Obstruction Increases Apoptosis and Deregulates Bcl-2 and Bax Expression in the Fetal Ovine Bladder

Urinary Outflow Obstruction Increases Apoptosis and Deregulates Bcl-2 and Bax Expression in the Fetal Ovine Bladder

Compliance of the obstructed fetal rabbit bladder

Morphological, stereological, and biochemical analysis of the mini‐pig urinary bladder after chronic outflow obstruction and after recovery from obstruction

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