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Biomedical subjects

L S Baskin

Publications and source records attributed to L S Baskin.

At least 73 records · Page 4Linked to original sources
PubMed1997

Cellular signaling in the bladder.

Embryologically, the urinary bladder is formed from endodermally derived epithelial cells and mesenchymal cells from the urogenital sinus and allantois. Experimentally, we have shown that bladder mesenchyme differentiates into bladder smooth muscle via an unknown signaling mechanism that originates from the urothelium. It is hypothesized that this signaling between the cellular types, occurs via growth factors. Evidence supporting this hypothesis is that a number of known growth factors, such as TGF beta 2 and 3, KGF and TGF alpha, as well as their receptors are regulated as a function of bladder development and are also modulated during experimental bladder outlet obstruction. Furthermore, growth factors most likely affect extracellular matrix degradative proteins which play a role in bladder remodeling during development, as well as in partial outlet obstruction. There is certainly impressive cellular communication that occurs during development and also occurs postnatally; such as during bladder injury. We have recently shown that KGF is directly responsible for the proliferation of urothelium during bladder injury. This normally quiescent cell, which in humans turns over once every six months to a year when injured, has the incredible ability to immediately proliferate covering the exposed areas of bladder muscle and submucosa. This proliferation is due to the direct effects of KGF, a classic paracrine growth factor which is secreted by the stromal compartment of the bladder and acts directly on the urothelium which harbors the receptor. The bladder also has an uncanny ability to regenerate. In a model to study the basic science behind bladder regeneration, a partial cystectomy was performed and an acellular tissue matrix devoid of all cellular elements was sutured to the defect. Within four days, the urothelium completely covered the acellular matrix, and within two weeks native smooth muscle was seen streaming into the acellular matrix in association with a new epithelium. It is hypothesized that cellular interactions between the epithelium and the mesenchyme, as we have shown in bladder differentiation, are encouraging the new growth of smooth muscle. For the bladder to be a safe and effective storage chamber the ideal cellular lining should be urothelium. Cells from the gastrointestinal are not optimal for this purpose since they either secrete or absorb electrolytes. We believe that the cellular interactions that occur between the urothelium and the foreign intestinal stroma will in time change the phenotype of the urothelium. Newer strategies for bladder replacement which take into account cellular signaling are critical for our young patients with neurogenic bladder disorders.

Animals↗
PubMed1997

Surgical repair of urethral circumcision injuries.

PURPOSE: The 2 types of urethral injury that can occur during circumcision are urethrocutaneous fistula and urethral distortion secondary to partial glans amputation. We report the surgical repair of these rare injuries. MATERIALS AND METHODS: In 8 patients urethrocutaneous fistulas located on the distal penile shaft or at the coronal margin were managed by splitting the glans and using a Mathieu style skin flap in 4 or vascularized penile skin flap in 4 to bridge the urethral defect. Three patients underwent repair of a hypospadiac deviated urethra secondary to partial glans amputation by 1 cm. of urethral mobilization and repositioning the meatus into a terminal position within the remaining glans tissue. RESULTS: The 8 patients with urethrocutaneous fistulas voided via a terminal meatus without fistula recurrence at a mean followup of 3.2 years (range 1 to 6). The 3 patients with partial glans amputation and urethral deviation repaired by short urethral advancement had functionally acceptable results, defined as a normal urinary stream, although 1 required meatal dilation postoperatively. CONCLUSIONS: The 2 types of urethral injuries that can occur during circumcision are a subcoronal urethrocutaneous fistula and scarred abnormal urethra from partial glans amputation. The urethrocutaneous fistula can be successfully repaired by splitting the glans and forming a neourethra from a vascularized pedicle flap of penile skin. The abnormal urethra after partial glans amputation is more difficult to repair but repositioning the urethra in a more cosmetic location has restored function.

Child, Preschool↗
PubMed1997

Neuroanatomical ontogeny of the human fetal penis.

OBJECTIVE: To determine the development of the human penis, and hence the cause of congenital anomalies, using an immunohistochemical analysis of fetal penile ontogeny. MATERIALS AND METHODS: In 25 human fetal penile specimens (gestational age 8 to 23 weeks) various tissues were localized immunohistochemically using stains for alpha-actin (smooth muscle), cytokeratin 8 and 14 (epithelium) and protein gene-product (PGP) 9.5 (neurons). RESULTS: Nerves were identified in the penis with anti-PGP in specimens of all ages, prominent dorsally at the 11 and 1 o'clock positions but also extending around the tunica to the junction of the corpus spongiosum and corpora cavernosa, suggesting that these structures may be injured in procedures which straighten the penis. The nerves continued into the glans on the dorsal aspect, suggesting that glans reduction in feminizing genitoplasties should be performed on the ventral aspect. Smooth muscle was first noted at 10 weeks' gestation, with epithelial differentiation occurring in the earliest specimens studied (8 weeks' gestation). With time, smooth muscle density was highest in the corpus spongiosum, especially between it and the corpora cavernosa. Smooth muscle also developed close to the urethral epithelium. The tunica albuginea showed consistent variations in thickness, with the mid-dorsal 12 o'clock position being the thickest, followed by the 5 and 7 o'clock periurethral positions. CONCLUSION: A better knowledge of penile development and of the relationship of the nerves to the corpora cavernosa is useful in the strategic design of penile straightening procedures and feminizing genitoplasties.

Actins↗
PubMed1997

Development and regenerative ability of bladder in the transgenic epidermal growth factor receptor gene knockout mouse.

PURPOSE: During embryogenesis we have previously shown that urothelium is essential for normal bladder growth and development. Urothelial growth may be mediated by peptides of the epidermal growth factor family, since the epidermal growth factor receptor is expressed in bladder urothelium and epidermal growth factor has been shown to induce deoxyribonucleic acid synthesis and migration of urothelial cells in vitro. Bladders from transgenic mice in which the epidermal growth factor receptor gene has been knocked out were used to examine the possible role of epidermal growth factor in bladder growth and development, detrusor neoformation and bladder regeneration. MATERIALS AND METHODS: Whole bladders from transgenic knockout mice 0 to 10 days old were surgically implanted into the "subdetrusor" space of adult athymic nude rat hosts. After 10 days the dome of the host rat bladder was resected with the distal half of the transplanted knockout mouse bladder. Augmentation cystoplasty was then performed on the host rat bladder using acellular tissue matrix with a portion of the acellular matrix sutured directly to the transplanted knockout mouse bladder. The animals were sacrificed 2 or 3 weeks postoperatively. To test the ability of knockout bladder tissue to regenerate into the transplanted matrix species specific Hoechst dye was used to determine whether the cells within the acellular matrix were of host (rat) or transplant (knockout mouse) origin. Immunocytochemical analysis was used to assess muscle neoformation. Controls consisted of wild-type mouse bladders from the same litter. Since epidermal growth factor receptor knockout mice usually die in the neonatal period, the role of the epidermal growth factor receptor signaling pathway in long-term muscle development was evaluated by transplanting knockout and wild-type control bladders under the renal capsule of athymic nude mouse hosts. These mice were sacrificed 30 days later and muscle development was assessed using immunocytochemical analysis. RESULTS: Histologically the transplanted acellular tissue matrix in the experimental and control animals appeared the same, containing well differentiated urothelial and smooth muscle cells that had migrated into the transplanted matrix. Staining with species specific Hoechst dye revealed that urothelial and smooth muscle cells transplanted from the knockout and wild-type mouse bladders invaded and regenerated in the transplanted matrix. There was no apparent difference in the amount of knockout or control mouse tissue in the transplanted matrix. Also, the long-term renal capsule transplants revealed no difference in the amount of smooth muscle in the epidermal growth factor receptor knockout and wild-type bladders. CONCLUSIONS: Signaling through the epidermal growth factor receptor pathway is not necessary for normal bladder development or bladder regeneration after injury.

Animals↗
PubMed1997

The effect of testosterone on androgen receptors and human penile growth.

PURPOSE: Recent rat studies suggest that early exposure to exogenous testosterone accelerates the loss of androgen receptors and compromises eventual penile length. In humans we hypothesize that down regulation of the androgen receptor is not the mechanism that stops penile growth. To test this hypothesis we investigated the effects of androgen deprivation and supplementation on the developing human penis. MATERIALS AND METHODS: A total of 15 normal human fetal penises at 7 to 19 weeks of gestation (mean plus or minus standard deviation 12 +/- 4.5) was divided in half sagittally. Specimens were grafted beneath the renal capsule of male athymic nude mice or nude rats. Three groups of host animals were prepared, including 10 with no testosterone that were castrated at grafting, 15 with testosterone and 5 with super testosterone in which 50 mg. testosterone propionate pellets were implanted subcutaneously at grafting. Each fetal penile specimen was its own control, since half was implanted into an intact animal and the other into a castrated or super testosterone host. Six weeks after grafting the specimens were analyzed for gross size (length), histology and expression of androgen receptors. RESULTS: All human fetal penile specimens grew from the nadir size and appeared as white exophytic growths on the surface of the host kidneys. Normal grafts were larger than castrate specimens (mean 6.9 +/- 2.1 versus 3.9 +/- 2.1 mm., p = 0.014). Mean length of the super testosterone specimens (7.3 +/- 2.3 mm.) was not significantly greater than that of normal specimens (p = 0.797). Histological analysis revealed that all specimens were composed of viable penile tissue. Cellular density of the castrate penises was approximately 2 times greater than that of the normal and super testosterone specimens (40.6 +/- 5.9 versus 25.1 +/- 2.8 cells per cm.2, p > 0.001), as calculated on enlarged micrographs. Supraphysiological doses of testosterone did not change the histology compared to controls. Immunohistochemical localization revealed androgen receptors expressed throughout the corporeal bodies, surrounding stroma and penile skin with intracellular localization to nucleus. The mean proportion of cells expressing androgen receptors was higher in the castrate (29.4 +/- 5.2 cells per cm.2) than in the normal (24.0 +/- 3.7) and super testosterone (24.7 +/- 4.5) grafts (p = 0.005). However, in regard to growth there was no change in the proportion of androgen receptor positive cells among the groups. CONCLUSIONS: Testosterone influences penile growth, possibly as a result of extracellular stromal expansion. The number of androgen receptor positive cells in the human fetal penis did not change among the castrate, normal and super testosterone hosts. These experiments support the hypothesis that penile growth cessation is mediated by mechanisms other than down regulation of the androgen receptor. Furthermore, these data support the hypothesis that early administration of androgen to prepubertal male individuals does not result in a shorter phallus in adulthood.

Humans↗
PubMed1997

Smooth and striated muscle development in the intrinsic urethral sphincter.

PURPOSE: The intrinsic urethral sphincter is composed of adjacent striated and smooth muscle. We studied the sequential expression of smooth and striated muscle proteins to gain insight into the ontogeny of intrinsic sphincter development. MATERIALS AND METHODS: The intrinsic urethral sphincters of timed Fischer 344 rat embryos at 14, 16 and 18 days of gestation, neonates on postnatal day 1 and adult animals were examined. Serial sections of the urethra and adjacent levator ani muscles were studied histologically with hematoxylin and eosin, anti-alpha-smooth muscle actin, anti-alpha-sarcomeric actin and antistriated muscle myosin heavy chain antibodies. RESULTS: The intrinsic urethral sphincter was identified within the periurethral mesenchyma as early as day 14 of gestation. Although striated myotubules were identified within the urethra by hematoxylin and eosin staining starting on postnatal day 1, striated muscle myosin heavy chain protein was absent in the embryonic and neonatal development of the sphincter, and it was expressed only in the mature myotubule of adults. alpha-Smooth muscle actin was expressed throughout the urethral sphincter of embryonic and neonatal animals. In adults alpha-smooth muscle actin was confined to the smooth muscle component of the urethra. Co-expression of alpha-smooth and alpha-sarcomeric muscle actin by the striated sphincter myotubule was noted only in neonates. CONCLUSIONS: Development of the intrinsic urethral sphincter is characterized by sequential expression of well characterized muscle marker proteins. The co-expression of smooth and striated muscle markers by developing sphincter myotubule suggests the possibility that trans-differentiation of smooth to striated muscle occurs in the developing genitourinary tract.

Animals↗
PubMed1997

The role of type IV collagenases in rat bladder development and obstruction.

The role of type IV collagenases during rat bladder development and in response to partial bladder outlet obstruction was evaluated. Gelatinase gel zymography was performed on developing rat bladders (gestation d 16 and 19, at birth, 5, 10, 15, 20, 30, and 75 d postnatally), after partial obstruction of the bladder outlet in young adults and after separation of the epithelium from the mesenchyme in young adults. Bladder function was assessed by cystometry in obstructed animals. During development, the 72-kD type-IV collagenase [matrix metalloproteinase (MMP)-2, both latent and activated] was maximally expressed in the fetal period and decreased with age; whereas the 92-kD gelatinase (MMP-9) was not expressed in developing or adult bladders. MMP-2 was localized to the bladder mesenchyme and was undetectable in isolated epithelium. In 46 obstructed rats, there was an 8-fold increase in bladder volume and weight along with smooth muscle hypertrophy (mean smooth muscle cell diameter 7.09 +/- 0.11 microns versus 4.65 +/- 0.05 microns in normal animals, p < 0.001). Obstructed rats had increased quantities of latent and activated MMP-2 and MMP-9 compared with sham-operated and normal controls. These findings suggest that expression and activation of type IV collagenases (MMP-2 and 9) are developmentally regulated and play a role in bladder remodeling during developmental morphogenesis and after partial outlet obstruction.

Animals↗
PubMed1997

Neurogenic bladder dysfunction due to myelomeningocele: neonatal versus childhood treatment.

PURPOSE: We sought to determine whether the neonatal institution of treatment of neurogenic bladder dysfunction in myelomeningocele patients at high risk for urinary tract deterioration improves renal and bladder outcome. MATERIALS AND METHODS: We reviewed the records of patients with bladder dysfunction believed to be at high risk for renal deterioration based on urodynamic studies. All patients were treated with clean intermittent catheterization. We compared rates of urinary infection, hydronephrosis, reflux, continence and surgical intervention in 46 patients in whom treatment was started in year 1 of life and 52 treated after age 4 years. RESULTS: Renal outcome was similar in both groups with persistent hydronephrosis in 6 of 46 patients (13%) and 7 of 52 (14%), respectively. However, significantly fewer bladder augmentation procedures were required in patients started on treatment during year 1 of life (5 of 46, 11% versus 14 of 52, 27%, p < 0.05). CONCLUSIONS: In addition to any psychological benefit, early intervention with clean intermittent catheterization in children with neurogenic bladder dysfunction may help to prevent irreversible bladder dysfunction and limit the need for bladder augmentation.

Age Factors↗
PubMed1997

Growth factors in bladder wound healing.

INTRODUCTION: Surgical and traumatic injuries to the bladder initiate a complex series of biological processes that result in wound healing. This process involves cellular proliferation, migration and differentiation; removal of damaged tissue; and production of extracellular matrix all of which may be controlled by growth factors. In skin, keratinocyte growth factor (KGF) is induced following incisional injury. We hypothesize that in bladder wound healing KGF and other growth factors are induced to modulate tissue repair. METHODS: We have created a model of surgical bladder injury in the rodent. At 12, 24 and 48 hrs and 5 and 7 days after injury, the bladder was bisected and total RNA extracted from the anterior or wounded half and posterior or non-wounded half. Histological analysis of the bladder wound was performed with Mason's Trichrome and immunohistochemistry against smooth muscle alpha actin. RNase protection assays were performed to examine the expression of KGF, transforming growth factor (TGF)alpha and TGF beta 2 and 3 as well as the receptors for KGF and epidermal growth factor (EGF). Lastly, the effects of the exogenous administration of KGF on the bladder was tested on neonatal mice by daily injections of 5 micrograms KGF per gram body weight for 5 days. RESULTS: At 12 hours after injury KGF mRNA expression in the anterior wounded bladder half and posterior non-wounded bladder half was 8 and 6 times higher respectively, compared to unoperated control bladders. A similar response was seen for TGF alpha, where the 12 hour mRNA expression was 4.5 times higher in the anterior wounded bladder half and 3.5 times higher in the posterior non-wounded bladder half compared to unoperated control bladders. The nadir mRNA expression for both KGF and TGF alpha occurred at 7 days after bladder injury and was the same as in unoperated control bladders. EGFR mRNA expression was approximately 2 times higher in both the anterior wounded and posterior non-wounded bladder halves compared to the nadir levels which occurred at 24 hours after injury. TGF beta 2 and beta 3 mRNA levels did not significantly change in either the anterior wounded or posterior non-wounded bladder halves. Exogenous KGF stimulation resulted in a marked urothelial proliferation when compared to age matched control animals. CONCLUSION: During the early phases of bladder wound healing (12-24 hours post injury), mRNA for KGF and TGF alpha increased, whereas TGF beta 2 and beta 3 and the KGFR and EGFR remain unchanged. Additionally, exogenous KGF has a direct effect on urothelial proliferation. KGF and TGF alpha warrant further study as potential mediators of bladder wound healing.

Animals↗
PubMed1996

Mesenchymal-epithelial interactions in the bladder.

During bladder development, undifferentiated mesenchymal and epithelial cells undergo an orderly sequence of differentiation defined by the expression of smooth-muscle (alpha-actin, myosin, vinculin, desmin, vimentin, and laminin) and epithelial (cytokeratins 5, 7, 8, 14, 18 and 19) protein markers. This process requires mesenchymal-epithelial interactions with bladder epithelium (urothelium) necessary for the differentiation of bladder smooth muscle. Peptide growth factors such as keratinocyte growth factor (KGF) and transforming growth factors (TGF) alpha and beta are likely candidates as mediators of these mesenchymal-epithelial interactions. Transcripts for KGF, TGF alpha, and TGF beta are regulated during bladder development and during smooth-muscle hypertrophy secondary to bladder-outlet obstruction. Finally, two experimental bladder models--(1) partial outlet obstruction and (2) regeneration of bladder smooth muscle into an acellular tissue matrix--are described in the context of mesenchymal-epithelial interactions in the bladder.

Animals↗
PubMed1996

Lower urinary tract function in ambulatory children with spina bifida.

OBJECTIVE: To investigate lower urinary tract function in ambulatory children with myelomeningocele. PATIENTS AND METHODS: The urological course of 45 children with myelomeningocele who walked either independently (19 children) or with ankle-foot orthotics (26 children) was reviewed. Follow-up ranged from 9 months to 13.5 years (mean 4.75 years). RESULTS: A normal pattern of voiding was observed both clinically and during urodynamic evaluation in only three of the 45 children, with the remainder displaying neurogenic lower urinary tract dysfunction. The independent walkers and those with orthotics did not differ in the spectrum of lower urinary tract dysfunction or other variables. Those patients with persistent incontinence underwent an initial urodynamic evaluation when older (mean 3.7 years versus 6.4 weeks in those who were continent). CONCLUSION: Ambulatory children with myelomeningocele suffer the full spectrum of lower urinary tract dysfunction. Given the potential danger of untreated lower urinary tract dysfunction, ambulatory children with myelomeningocele should receive the same diagnostic and therapeutic attention as their peers with more overt neurological deficits.

Adolescent↗
PubMed1996

Regeneration of bladder urothelium, smooth muscle, blood vessels and nerves into an acellular tissue matrix.

PURPOSE: To study the cellular events occurring during bladder development and regeneration we developed an in vivo model of bladder augmentation with an acellular tissue graft. We propose that the extracellular matrix orchestrates the regenerative capacity of host bladder cells (urothelium, smooth muscle, blood vessels and nerve cells) after bladder augmentation with acellular tissue matrix. MATERIALS AND METHODS: A total of 40 adult rats underwent partial cystectomy and augmentation with a patch of extracellular matrix representing the full thickness of rat gastric or bladder tissue. Sections were examined histologically to assess urothelial, smooth muscle and neuronal invasion of the graft. RESULTS: A total of 32 rats was evaluated 1 day to 26 weeks after grafting. Epithelialization occurred by day 4, accompanied by granulocytic infiltration. Smooth muscle regenerated 2 weeks after grafting in juxtaposition to epithelial surfaces and it matured into normal sized bundles by 26 weeks. Neovascularity was noted 2 weeks postoperatively. Neural elements formed around developing smooth muscle bundles as early as 4 weeks after grafting. CONCLUSIONS: We demonstrated the regeneration of urothelium, smooth muscle, blood vessels and nerves within a full thickness grafted acellular tissue matrix scaffold in the rat. The spatial orientation of these elements suggests that mesenchymal-epithelial interactions occur during phenotypic regeneration of the bladder. Urothelium appears to regulate the early forming smooth muscle. This in vivo model provides a suitable method to study cellular events during regeneration.

Animals↗
PubMed1996

The effect of prepubertal androgen exposure on adult penile length.

PURPOSE: Recent studies in the rat suggest that early exposure to exogenous testosterone accelerates the loss of androgen receptors and compromises eventual penile length. To determine whether this is true in men we measured adult penile length of patients treated in childhood for sexual precocity. MATERIALS AND METHODS: We examined 21 men with sexual precocity due to true precocious puberty (12) or congenital adrenal hyperplasia (9) who had been followed at our institution since childhood. Penile lengths were compared with data from normal men. RESULTS: Mean stretched penile length plus or minus standard deviation was 12.7 +/- 2.6 cm. in all patients, 12.1 +/- 2.6 cm. in those with true precocious puberty and 13.6 +/- 1.6 cm. in those with congenital adrenal hyperplasia. These lengths were not significantly different from those of normal men (12.4 +/- 2.7 cm.). CONCLUSIONS: In contrast to findings in rats, exposure to endogenous testosterone during gestation and/or childhood does not reduce adult penile length in men. Thus, the use of testosterone to treat childhood genitourinary anomalies would likely not compromise mature penile size.

Adrenal Hyperplasia, Congenital↗
PubMed1996

Epithelial development in the rat ventral prostate, anterior prostate and seminal vesicle.

The prostate and seminal vesicle (SV) are androgen-dependent secretory glands of the male genital tract. The epithelial cells of these glands produce the bulk of the seminal secretions. The objective of the present study was to examine the ontogeny of cytokeratin and androgen receptor (AR) expression in the rat SV, anterior prostate (AP) and ventral prostate (VP). The study utilized organ culture to examine the effects of androgens on the development of these markers and castration of adult rats to examine androgenic effects on their maintenance. Tissues were examined from 14 days of gestation to adulthood. The SV was a tubular organ from its inception while the prostate formed from solid epithelial cords. These prostatic buds canalized in a proximal to distal manner starting at day 1 postnatal in the VP and day 5 in the AP. The expression of cytokeratins and AR was visualized by immunocytochemistry. In all three glands keratins 5, 7, 8, 14, 18 and 19 were initially uniformly expressed in all epithelial cells. In the SV, segregation of cytokeratins between the luminal and basal cell types started at 4 days postnatally with keratin 7 localizing to basal cells. Five days after birth, keratins 5 and 14 were also localized to the basal epithelium, while keratins 8 and 18 were only expressed by luminal cells, Keratin 19 was expressed in all epithelial cells throughout development and into adulthood. In the VP and AP the same pattern of cytokeratin segregation occurred as in the SV. Epithelial differentiation occurred in a proximal to distal fashion in the prostate. In the proximal VP ducts keratins 7 and 14 were basally localized by 2 days postnatally, while keratin 5 did not clearly segregate to basal cells until day 9 after birth. In the AP keratin 14 was basally localized by 1 day postnatal but keratin 5 and 7 did not colocalize to the basal cells until days 9 and 12, respectively. AR were expressed in the epithelium of the urogenital sinus from 19 days of gestation. At 19 and 20 days of embryonic development AR-negative prostatic buds were seen emerging from the AR-positive urogenital sinus epithelium. By birth AR were detectable in the epithelium of both prostatic lobes and the SV. The role of androgens in the development of the prostatic and SV epithelium was investigated in a serum-free organ culture system. These experiments showed that differentiation of prostatic and SV luminal and basal epithelial cell types was accelerated as compared to the in vivo situation in the presence of androgens, and did not occur in their absence. Following castration of adult animals the prostate and SV regressed with preferential loss of luminal epithelium. The relative numbers of basal cells was increased, though some flattened cells expressing a luminal cell pattern of cytokeratins were still observed. AR were detected in the prostatic and SV epithelium of long-term castrated animals. In summary, the rat prostate was found to be derived from undifferentiated solid epithelial cords. Canalization occurred concurrent with the differentiation of clear epithelial subtypes. Epithelial AR were expressed from around the time of birth and expression levels increased with age. The SV was canalized from its inception but likewise was derived from an undifferentiated epithelial precursor.

Age Factors↗
PubMed1996

Stromal development in the ventral prostate, anterior prostate and seminal vesicle of the rat.

The prostate and seminal vesicle (SV) are androgen-dependent secretory glands of the male genital tract. They produce the bulk of the seminal secretions. The object of the present study was to examine and document the ontogeny of stromal maturation in the rat anterior and ventral prostate and SV. These organs have a loosely organized cellular mesenchyme during fetal development. During prostatic development the mesenchyme condensed to form smooth muscle sheaths immediately surrounding the epithelium, with looser connective tissue between individual ducts. In the SV, a loose connective tissue layer called the lamina propria lies between the epithelium and developing muscle. Smooth muscle alpha-actin, myosin, desmin, laminin, vinculin, vimentin and androgen receptor (AR) expression were examined by immunocytochemical methods during the pre- and postnatal developmental periods. The first marker to be detected was vimentin, which was initially found throughout the mesenchyme. During development vimentin became mostly restricted to the interductal tissue of the prostate and the lamina propria of the SV. Smooth muscle markers were expressed in an orderly sequence in a proximal to distal manner along prostatic ducts, from the urethra towards the tips. Expression of alpha-actin was followed by vinculin, myosin, desmin, and laminin. These markers became localized to the developing smooth muscle sheaths and were not expressed in the interductal tissue of the prostate or the lamina propria of the SV. Organ culture experiments demonstrated that androgens were required for the differentiation of smooth muscle sheaths. Castration of adult rats demonstrated that androgens were required to maintain smooth muscle differentiation. In castrates, the stroma was relatively thicker but less dense than in intact animals. Following castration, expression of the smooth muscle markers was lost sequentially in the reverse order of their expression during development. In long-term castrates alpha-actin, vimentin and a small amount of vinculin were detected. AR were first detected in the urogenital sinus mesenchyme immediately surrounding the epithelium at 16 days of gestation. As development progressed expression of AR became more widespread, and postnatally was found throughout the mesenchyme. As maturation of smooth muscle occurred, stromal expression of AR became localized to the muscular sheath immediately surrounding the epithelium. In the prostate the interductal connective tissue displayed very low levels of AR expression. In the SV, AR were also observed in the lamina propria. In summary, stromal differentiation and dedifferentiation in the rat prostate and SV were found to be androgen-dependent processes with ordered sequential ontogenic expression of specific markers.

Actins↗
PubMed1996

Ontogeny of the rat bladder: smooth muscle and epithelial differentiation.

The sequential expression of smooth muscle and epithelial markers in the rat bladder has been defined. Smooth muscle differentiation, based on cell morphology and immunohistochemical localization of smooth muscle alpha-actin, myosin, vinculin, desmin, vimentin and laminin, begins at 16 days of gestation (birth = 22 days) in the rat bladder. Smooth muscle cell differentiation begins in the periphery of the bladder mesenchyme immediately subadjacent to the serosa and continues toward the urothelium. The cytokeratins 5, 7, 8, 14, 18, and 19 are expressed in the bladder epithelium as a function of developmental age with cytokeratin 7, 8, 18, and 19 being coexpressed at 15 days' gestation followed by cytokeratin 5 at 17 days' gestation and cytokeratin 14 in the newborn bladder. An understanding of the ontogeny of both smooth muscle and epithelial differentiation markers in the normal bladder will allow us to study events that occur in the diseased bladder.

Animals↗