In shape the prostate resembles a Spanish chestnut. Todd’s Cycl. Anat., IV, 146/1, 1847–9 Very little is known as to the uses of the prostatic body. Todd’s Cycl. Anat. II, 459/1, 1836–9
Development of the prostate, seminal vesicles, and urethral sphincters
Prostate
The prostate is formed after differentiation of the urogenital sinus and the development of the wolffian structures (see Fig. 13-9 ).
The utricular cord; the müllerian and wolffian ducts
The müllerian (paramesonephric) ducts fuse in the midline to form the solid utricular cord between the wolffian ducts ( Fig. 14-1 ). The cord impinges on the wall of the urogenital sinus at the junction of the vesicourethral canal (the portion that will become the bladder) and the pelvic portion of the urogenital sinus (that will form the prostatic urethra).
Formation of the müllerian tubercle
The utricular cord becomes canalized ( Fig. 14-2 A).
Where the cord impinges on the dorsal wall of the urogenital sinus, forming the müllerian (sinus) tubercle, the endodermal lining of the sinus is stimulated and extrudes to form the sinoutricular cord with the mesoderm of the utricular cord ( Fig. 14-2 B, see also Fig. 13-9 ).
As the müllerian ducts atrophy, the fused residual, distal portion and the attached sinus portion of the sinoutricular cord become canalized ( Fig. 14-2 C). It has been shown that the utricle forms as an ingrowth of specialized cells from the dorsal wall of the urogenital sinus as the caudal müllerian ducts regress. The müllerian tubercle remains as the verumontanum or colliculus seminalis.
In the female, the sinus forms the introitus and the utricular cord forms the vagina, as described in Fig. 15-6 .
Preprostatic and posterior urethra
The primary or preprostatic urethra originates from the vesicourethral canal, which is that part of the urogenital sinus lying above the müllerian tubercle (verumontanum) ( Table 14-1 ). This section examines the entire urethra in the female.
| PREPROSTATIC URETHRA |
| From portions of urogenital sinus. Extends from above entrance of müllerian and wolffian ducts to junction with bladder. |
| POSTERIOR URETHRA |
| From the pelvic part of the urogenital sinus. Extends from above the level of the duct openings to urogenital membrane. |
| DISTAL URETHRA |
| From the phallic part of the urogenital sinus as a groove between the urethral folds, elongating with growth of genital tubercle. |
The posterior urethra proper is formed from the pelvic part of the urogenital sinus ( Fig. 14-3 A).
It begins immediately above the level of the openings of the wolffian and müllerian ducts and extends to the urogenital membrane. Epithelial extensions from the proximal portion will form the prostatic lobes. The phallic part of the urogenital sinus forms the bulbar and penile sections of the urethra (see Fig. 16-3 ).
In the adult, the prostatic utricle is a shallow depression on the verumontanum, which is flanked distally by the openings of the ejaculatory ducts ( Fig. 14-3 B). The collicular folds (seminal colliculi) lie on either side of the verumontanum, closely associated with the openings of the sets of prostatic ducts. The folds are derived from wolffian elements and appear as paired longitudinal striations in the lateral wall of the more proximal portion of the urogenital sinus (see Fig. 13-11 ). They extend distally from the müllerian tubercle to the site of origin of the bulbourethral glands, which in early development are situated anteriorly. Later, as the wolffian ducts regress and move more proximally, the folds move with them, fostered by regression of their most distal portions. They also move laterally by growth of the urethra.
The epithelium of the collicular folds differs from that of the rest of the urethra. It contains appreciably less prostatic acid phosphatase than the rest of the prostatic urethra.
Formation of the prostatic ducts
The primitive prostatic ducts develop under the influence of wolffian duct mesenchyme in close association with the wolffian duct in the prostatic urethra.
Fetal androgens produced by the testis beginning in the eighth week are a prerequisite to this mesenchymal activity. As Leydig cells differentiate, androgen levels in testicular tissue rise. The enzyme 5-alpha reductase is produced in the end-organ to convert testosterone into dihydrotestosterone.
Between the 11th and 12th weeks, the mesenchyme surrounding the prostatic urethra is stimulated by androgens to induce proliferation of the epithelium, evidenced first by the budding of the primary ducts, then by the formation of branches from the urethral epithelium. At this time, the ducts appear as solid epithelial outgrowths within an area of smooth muscle fibers and dense connective tissue both proximal to the entrance of the wolffian duct (in the preprostatic urethra) and distal to it (in the urogenital sinus) in an area that is demarcated from the surrounding mesenchyme. The ducts develop principally on the dorsal wall, less densely on the lateral wall, and rarely in a ventral position. Lowsley counted 63 branches in a 13-week-old fetus. The ducts are solid at first; after 30 weeks, they acquire lumens. At first, small collections of cellular buds develop, then acinar structures appear. Later, lobular clusters of acinotubular structures develop as the ducts invade the mesenchyme surrounding them.
Zonal distribution
The ducts arise from three areas in the epithelium and contiguous mesenchyme of that part of the urogenital sinus destined to become the floor of the prostatic urethra ( Fig. 14-4 ). Each of the three sets of ducts will drain one of the three zones of the prostate (see also Figs. 14-24 , 14-27 , 14-29 , 14-30 , 14-31 , and 14-32 ).
The earliest set buds distal to the verumontanum and becomes the peripheral zone of the prostate.
A second set branches from the urethra in two rows that lie beside and above the site of exit of the ejaculatory ducts in the verumontanum in an area populated by epithelium from the wolffian ducts. This set will become the central zone of the prostate in the male and will form the paraurethral glands in the female.
The ducts of the peripheral zone are thought to arise from the tissue of the urogenital sinus, whereas those of the central zone come from the intrusion of wolffian duct material into the tissue of the urogenital sinus.
A third set of buds, situated most proximally in the vesicourethral canal, will proliferate within an inner submucosal zone to form the ducts and glands of the transition zone in the male, homologues of the urethral glands in the female. These glands remain small in size and uncomplicated in structure and do not develop intrinsic musculature.
For the transition zone, well-differentiated acini develop; at first, periurethrally along the preprostatic urethra on the luminal side of the preprostatic sphincter proximal to the site of the future peripheral and central zones. The sphincter becomes thinner as it approaches the proximal end of the peripheral zone near the verumontanum. This allows a special group of larger and more complex periurethral glands to expand peripherally and centrally to form the transition zone. Their ducts at first run parallel to the urethra and then turn medially when they reach the distal end of the preprostatic sphincter.
In this zone, both sinus and wolffian tissues are probably involved in competition for the space between the urethral lining and the musculature of the urethral wall (preprostatic sphincter). The result of such interposition is a somewhat unstable embryologic development. With aging, this area reverts to a more elemental state in which the stroma proliferates and induces glandular formation, resulting in benign prostatic hyperplasia.
Histologic characteristics.
The three zones have different cellular characteristics and show different responses to hormonal stimulation (see Figs. 14-33 , 14-34 , and 14-35 ). The distal two zones might be considered analogous to the double set of prostate glands of subhuman primates. The central zone develops more rapidly than the peripheral zone during early puberty and atrophies later with aging, suggesting that it is less dependent on androgens. Perhaps the transition zone should not be considered part of the prostate proper because the glands are essentially periurethral, have a different mode of origin at a different site, and have a different response to aging and neoplasia. Benign prostatic hyperplasia develops only from this zone; carcinoma begins here less often than it does in the other zones.
Prostate-specific antigen, appearing at 28 weeks, shows a weaker reaction in all areas of the developing prostate than in the mature prostate. Prostatic acid phosphatase activity appears at the same time as prostate-specific antigen and is variable in its activity, being highest in the lateral areas of the peripheral zone.
The subcervical glands (Albarrán) develop about the 16th week from the urethral floor at and below the level of the internal sphincter. Hyperplasia of these glands may produce a distinctive exophytic nodule of prostatic tissue at the bladder neck, projecting into the vesical cavity, often referred to as median lobe hyperplasia ( Fig. 14-5 ). A few subtrigonal glands are found in the 20th week.
The bulbourethral glands (Cowper) form as epithelial buds from the pelvic part of the urogenital sinus and grow through the mesenchyme of the corpus spongiosum ( Figs. 14-6 and 14-7 ; see also Fig. 14-56 ). Once past this tissue, they branch and develop lumens. The greater vestibular glands (Bartholin) are the homologous structures in the female. The forerunners of the urethral glands (Littré) appear successively, starting anteriorly as endodermal buds around the walls of the phallic part of the urogenital sinus.
The ejaculatory ducts develop as the termination of the wolffian duct. The deferential branches from the vesicodeferential arteries pass through the posterior surface of the prostate between the central and peripheral zones on the way to supply part of the verumontanum.
Squamous metaplasia develops in regions derived from the müllerian ducts. It is uniformly present about the prostatic utricle, common in the ejaculatory ducts, and less common in the posterior urethra.
The prostatic ducts proliferate and show signs of secretion between 5 and 6 weeks’ postpartum. Alveoli are subsequently formed. The metaplasia of the alveolar epithelium and verumontanum that had been induced by maternal hormones is reversed and the prostate remains essentially unchanged until puberty. During the 6 or 7 years after puberty, the gland rapidly enlarges to reach its mature size. Later in life, the epithelial complexity decreases at the same time that the periurethral glands of the transition zone are induced by the stroma to differentiate and form benign hyperplasia.
Smooth muscle sphincters
Development of the preprostatic and urethral smooth muscle sphincters
The smooth muscle of the bladder outlet and that of the preprostatic urethra are formed independently but become continuous during subsequent development. Muscle fibers differentiate in layers from mesenchymal cells with the same orientation. Thus, very early in fetal life, three smooth muscle systems can be detected: (1) the musculature of the bladder base, (2) the smooth urethral musculature, and (3) the prostatic smooth musculature, which develops independently of the other two ( Fig. 14-8 ).
The bladder base segment is composed of the deep and superficial trigonal systems. The circular fibers forming the deep trigone develop first at 3 weeks to form the trigonal ring. A week later, the longitudinal fibers of the superficial trigone related to the ejaculatory ducts and the ureteral musculature appear and extend from the verumontanum to the ureteral orifices (see Figs. 13-11 and 13-12 ).
The urethral smooth muscle that will form the preprostatic sphincter appears around 5 weeks of gestation as two layers: (1) an inner longitudinal and (2) an outer more or less obliquely oriented circular layer. These layers arise separately from those of the bladder and are not connected to the detrusor at this stage. Only later and secondarily do they become continuous with the corresponding longitudinal and circular muscles of the bladder neck.
Ultimately, they form both the preprostatic sphincter and the passive prostatic sphincter. The preprostatic sphincter, as noted, is closely related to the formation of the adjacent transition zone.
The prostatic musculature develops in the outer stromal layer of the primitive prostate synchronously with that of the bladder neck. The slender fibers are distinguishable from the coarser smooth muscle of the trigone and the urethra as they surround the urethra except for the dorsomedial wall.
Striated sphincters
Early development of the striated sphincter
At 5 weeks, before the primitive prostatic ducts are formed, the primordium of the external striated urethral sphincter is in place over the transverse bundles of smooth muscle of the ventral wall of the prostatic urethra. Now clearly striated, the primordium develops dorsally and makes contact with the rectal musculature at the site where the rectourethralis will develop.
By 9 weeks, the striated sphincter , which will differentiate into the prostatic striated sphincter and the membranous urethral sphincter, covers the ventral side of the urethra all the way to the bladder neck ( Fig. 14-9 ). On the dorsal side, the muscle coat is incomplete because the entry of the müllerian and wolffian ducts limits its proximal distribution. Here, the muscle has the shape of a horseshoe, becoming doughnut-shaped distally as it encircles what will become the membranous urethra. Cranially, the bundles insert into the prostate and their free ends attach to the dorsal raphe.
Glandular development
The mucosal buds expand from the dorsum of the urethra on both sides and develop into lobes as they intrude against the striated musculature. The two lateral portions of the developing prostate fuse in the midline anteriorly, forming the anterior commissure, which is complete proximally but may be incomplete distally. The growth of the prostate thins the muscle surrounding the prostatic urethra ventrally and laterally.
The striated sphincter not only covers the smooth urethral musculature and immature prostate but also inserts into the prostatic substance in the capsule and is in contact with the circular muscle of the fundus ring.
Development of the striated sphincter after birth
At term, the prostatomembranous sphincter extends along the urethra from the bladder neck to the perineal membrane . The proximal portion of the sphincter, called the prostatic striated sphincter, is most developed over the central part of the prostate, where it extends three-quarters of the way around ( Fig. 14-10 ). At the caudal end, where the distal portion of the sphincter meets the pelvic floor, the membranous striated sphincter lies above the perineal membrane between it and the so-called superior layer of the urogenital diaphragm. Here, the muscle is distributed more uniformly around the urethra but is still relatively deficient dorsally. As the prostate develops bilaterally around the urethra to meet in a ventral commissure, the fibers of both prostatic sphincters are displaced and thinned. These changes account for the difficulties that have been encountered in describing them accurately. Moreover, the prostatic lobes may not join distally at the commissure, thus allowing direct contact between sphincter and urethra.
By 4 years of age, the striated sphincter has extended from the trigonal ring to a point slightly beyond the transverse perineal muscle. Evidence that a true urogenital diaphragm does not form is that the sphincters do not lie above it.
Development of the prostatic sheath and denonvilliers’ fascia
Prostatic sheath
The prostate and seminal vesicles are enclosed in a loose fascial coat developed from the middle stratum of the retroperitoneal connective tissue as part of the umbilicovesical fascia, the same fascia that forms the puboprostatic ligaments.
Denonvilliers’ fascia, anterior lamella
During early development, after the descent of the urorectal septum, the peritoneal cavity separates the urogenital sinus from the hindgut, so that the posterior surfaces of the bladder, seminal vesicles, and prostate are covered with a double layer of fusion-fascia derived from the two layers of peritoneum that lined the rectovesical pouch. The two apposed peritoneal coats have fused distally to proximally, and the mesothelium is subsequently resorbed, leaving as fusion-fascia the two underlying layers of the inner stratum of retroperitoneal connective tissue to constitute the anterior lamella of Denonvilliers’ fascia (see Fig. 14-25 ). The periprostatic tissue (prostatic sheath), derived from the intermediate stratum of the retroperitoneal connective tissue, is anterior to this fascia.
Denonvilliers’ fascia, posterior lamella
The loose mesenchymal tissue of the inner stratum of retroperitoneal tissue over the rectum becomes organized into a sheet covering the anterior and lateral surfaces of the rectum after the descent of the urorectal septum into the pelvis (migration fascia). This sheet, the rectal fascia, forms the posterior lamella of Denonvilliers’ fascia.
Thus, embryologically, four layers are formed between prostate and rectum: one from the intermediate stratum that forms the prostatic sheath, two layers associated with the peritoneal mesothelium that fuse to form the anterior lamella of Denonvilliers’ fascia, and one from the inner stratum, the posterior lamella of Denonvilliers’ fascia.
An alternative explanation that does not invoke peritoneal fusion and accounts for the smooth muscle fibers in Denonvilliers’ fascia is that the apparent upward migration of the rectovesical pouch occurs by condensation of the loose areolar tissue overlying the rectum. Other opinions exist for the origin of Denonvilliers’ fascia, for example, that it is a wolffian derivative.
Development of the seminal vesicles
In the sixth month, the seminal vesicles and ampullae become very large at the same time that the growth of the prostatic tubules is accelerated.
A mound rises at the juncture of the wolffian duct with the derivatives of the urogenital sinus at the end of the third month, at the time of degeneration of the müllerian ducts ( Fig. 14-11 A). This swelling will form the seminal vesicles and the ampulla of the vas. As the remains of the wolffian ducts, the vasa deferentia appear as two small tubular structures under the bladder between the ureters. They are contained in a thick muscular and connective tissue coat. The coats between the vasa merge beneath the vesical neck, where the vasa are very large. Lateral branches appear on each vas, signally the initial development of the seminal vesicles ( Fig. 14-11 B). After becoming demarcated from the ampullary portion, the seminal vesicle elongates, acquires a distinct duct, and develops sacculations in the wall ( Figs. 14-11 C-F). In time, as the first branches grow dorsolaterally, they become tortuous and each produces up to four similarly tortuous branches. The vesicular ducts are connected with the vasa deferentia within the substance of the prostate.
Distal to the vesicular branches, the vas deferens, as the ejaculatory duct, has a smaller lumen surrounded by less abundant tissue as it fuses with the muscular coat of the urethral wall ( Fig. 14-11 F).
At the same time, above the site of vasal fusion, the fused müllerian ducts retain a small lumen within a delicate connective tissue cover. Distally, the lumen becomes greatly enlarged to form the prostatic utricle, but it subsequently contracts so that after the 22nd week, it can be found only as a pocket (the prostatic utricle ) just below the openings of the prostatic ducts ( Fig. 14-11 C).
Anomalies in the male
The anomalies associated with the abnormal development of the müllerian and wolffian ducts are listed in Table 14-2 . All of them are rare and, except for absence of wolffian derivatives, are of little clinical significance.
| Anomaly | Age (Weeks) | Time of Appearance |
|---|---|---|
Müllerian and mesonephric remnants in the male:
| Adolescence | |
| Testis or appendix | ||
| Epididymis | ||
Absence of wolffian derivatives in the male:
|
|
|
| Duplication of the ductus deferens | Late 4 | None |
| Absence of the seminal vesicle | Before 12 | Adulthood only if bilateral |
| Duplication of the seminal vesicle | 12 | Never |
Anomalies of the prostate gland:
| 12 | Adulthood |
Congenital urethral valves
Abnormalities of the collicular folds, the wolffian derivatives that arise as longitudinal striations in the posterolateral wall of the more proximal portion of the urogenital sinus below the verumontanum, are responsible for most urethral valves (see Fig. 14-3 B).
Three types of valves are recognized ( Fig. 14-12 ). Type I valves are sail-like exaggerations of the collicular folds that extend from the müllerian tubercle to the site of origin of the bulbourethral glands distal to the verumontanum ( Figs. 14-13 and 14-14 ). Because the folds are attached on the anterolateral walls of the urethra, when fully developed, they may effectively block the passage of urine as they are filled by the flow of urine. The rare Type II valves run from the verumontanum toward the bladder. Both Types I and II may be the result of abnormal insertion and failure of cephalad regression of the wolffian ducts, leaving the collicular folds to assume an abnormal shape. The Type III valve is actually a diaphragm with a small opening in the center that lies either above or below the verumontanum ( Figs. 14-15 and 14-16 ). It probably represents the residua of the urogenital membrane.
Enlarged prostatic utricle
The prostatic utricle forms as an ingrowth of specialized cells from the dorsal wall of the urogenital sinus as the caudal müllerian ducts regress. Its size usually diminishes in the ninth week, but in some cases of hypospadias and intersexuality a deep utricle is found; its size is generally inversely proportional to the degree of hypospadias. Cystic dilatation of the utricle may occur, and in some cases of this entity there is a direct connection between the cavity of the utricle and the urethra; absence of such a communication results in a prostatic utricular cyst.
Prostate, urinary sphincters, and seminal vesicles: structure and function
Prostate
Prostatic relationships
The prostate has a somewhat pyramidal shape, with a base against the bladder and an apex joining the membranous urethra. The posterior surface is flattened and slightly depressed in the midline, which is evidence of the bilobar character of the gland. This surface lies against the rectal ampulla, with the two lamellae of Denonvilliers’ fascia intervening. More laterally, the prostate rests on the anterior projections of the levator ani that form the pubococcygeus muscles, which, with the puborectalis and iliococcygeus, overlie the obturator internus ( Fig. 14-17 ).
Surgical exposure is not easy because the prostate lies deep in the pelvis behind the pubic symphysis, wedged between the levators.
Prostate and adjacent structures, sagittal section
The base of the prostate abuts the bladder base superiorly. Posteriorly, in company with the seminal vesicles and ampullae of the vasa, it rests on the surgically important anterior lamella of Denonvilliers’ fascia ( Figs. 14-18 and 14-19 ). Beneath this fusion-fascia is the posterior lamella of Denonvilliers’ fascia, a layer of rectal fascia.
The deepest extension of the rectovesical pouch in the adult lies about 6 cm above the anus; it always ends above the tip of the coccyx, opposite the fourth or fifth part of the sacrum and well above the base of the prostate gland.
Denonvilliers’ fascia covers the posterior wall of the prostate as a loose layer of connective tissue dispersed about areolar spaces filled with fat, vessels, and nerves. This description is contrary to that in most reports, which present a dense two-layered system. When exposed perineally, Denonvilliers’ fascia appears as a white surface, but on microscopic inspection, it is seen to be composed mainly of areolar tissue. However, it is an identifiable surgical layer and does form a barrier between prostate and rectum, because rarely do neoplasms extend from one organ to the other.
The apical portion of the prostate and the first part of the membranous urethra are firmly attached by the rectourethralis muscle to the lower anterior rectal wall.
The prostatic striated sphincter partially covers the anterior surface of the prostate; it is continuous distally with the membranous urethral sphincter. The prostate is separated from the posterior surface of the pubis by the rather deep retropubic space (Retzius), containing the prostatic venous plexus (Santorini). The plexus is in continuity with the deep dorsal vein of the penis.
The preprostatic urethra and the prostatic urethra traverse the prostate in succession from the vesical neck to the apex. The urethra then passes through the membranous urethral sphincter and the two poorly characterized layers of the so-called urogenital diaphragm to join the bulbous urethra.
Structures related to the prostate, coronal-sagittal view
The prostatic venous plexus is embedded in the periprostatic fascia, a layer derived from the intermediate stratum, shown here reflected from the anterior surface of the prostate ( Fig. 14-20 ). The plexus lies over the anterior fibromuscular stroma and some of the lateral surface of the prostate. The prostate is separated laterally by a few millimeters of connective tissue sheath from the pelvic portion of the outer stratum of the retroperitoneal connective tissue, called the endopelvic (lateral pelvic) fascia. This fascia, overlying the pubococcygeus, is continuous with the obturator fascia covering the obturator internus . Superiorly, the base of the prostate joins the vesical neck. The bulbourethral glands (Cowper) lie above the perineal membrane (inferior layer of the urogenital diaphragm). The pudendal vessels and nerve pass through the pudendal canal (Alcock) inferolateral to the prostatic striated sphincters.
Puboprostatic ligaments and dorsal vein complex
Viewed from above, the anterior surface of the prostate is held behind the pubic symphysis by the paired puboprostatic ligaments (median puboprostatic ligaments) ( Fig. 14-21 ). Each ligament is 4.5 mm wide and is attached to the perichondrium near the inferior border of the symphysis pubis lateral to the synchondrosis, and each deviates slightly medially before becoming continuous with the fascial sheath overlying the prostatovesical junction. In prostates enlarged by benign hyperplasia, the ligaments become thin and less well-defined, and are attached more distally to the prostatic sheath and capsule. Branches of the deep dorsal vein that drains the penis run beneath and between the puboprostatic ligaments, forming the dorsal vein complex, the distal part of the prostatic venous plexus. The deep dorsal vein also provides connections with the lateral part of the prostatic venous plexus, which, in turn, empties into the vesical plexus to terminate in the middle hemorrhoidal and inferior vesical veins.
The dorsal vein complex and the veins of the prostatic plexus cushion the prostate against the symphysis. The puboprostatic ligaments contain smooth muscle that provides a flexible attachment for the prostate so that it, with its sphincters, is free to descend during relaxation of the pelvic floor before micturition.
Posteriorly, the rectourethralis forms a connection between the rectum and the prostatic apex.
Prostatic urethra
The urethra traversing the prostate is between 3 and 4 cm long, extending from the vesical neck to the membranous urethra . It is not straight because the urethra above the verumontanum is tilted anteriorly at a 45-degree angle from the vertical plane. The most proximal part of the urethra lies in the anterior portion of the prostate, its course running deeper into the prostatic substance as it descends to the verumontanum (see Fig. 13-57 ).
Although the prostate is thought of as a single organ, it is actually dual, perhaps homologous with the two distinct prostates found in nonhuman primates. Because of differences in development and function, the prostate has been divided into two regions ( Fig. 14-22 ). One is the preprostatic region, involved with the transition zone of the prostate. This region extends from the vesical neck to the entrance of the ducts that drain this zone lying immediately above the openings of the ejaculatory ducts. The other is the prostatic region that extends to the apex at the membranous urethra. This region involves the majority of the prostatic tissue with its ducts emptying lateral to the ejaculatory ducts.
