DEVELOPMENT OF THE UROGENITAL SYSTEMS II. Genital System Development The development of the genital system and sexual characteristics follows an orderly sequence of events including the determination of genetic sex, gonadal sex, ductal sex, genital sex, secondary sex characteristics, and phenotypic sex. 1. The genetic sex of the embryo is determined at fertilization is morphologically apparent in the gonads during the 1st month of embryonic development may be determined by the presence or absence of sex chromatin in the nuclei of cells obtained by amniocentesis A and C only A, B and C Right! No, the answer is D. Genetic sex is determined at fertilization by the type of sperm (X or Y) which fertilizes the ovum. There is no morphological indication of sex until approximately the 7th week although the chromosomal sex of embryos may be determined by the use of cresyl-echt violet to detect a second X chromosome or quinacrine mustard to stain the Y chromosome. 2. Which of the following is (are) true of gonadal development before the 7th week of embryonic life, the gonads of both sexes exist in an indifferent stage persistence of the cortex occurs under the influence of the Y chromosome and results in the development of a testis from the indifferent gonad the fetal testis will differentiate later than the fetal ovary A and C only A, B and C Right! No, the answer is A. Gonadal sex development results in the differentiation of the indifferent gonad into a testis or ovary. Primordial germ cells, which arise in the endoderm of the yolk sac, migrate to the genital ridge of the embryo and eventually enter the gonad directing gonadal differentiation. The indifferent gonad consists of 2 parts cortex and medulla. The presence of a Y chromosome results in the persistence of the medullary portion of the indifferent gonad and the development of a testis. The fetal testis will develop before the ovary. 3. Ductal sex is dependent on the presence or absence of androgens, produced by the fetal testis begins with an indifferent stage in which both paramesonephric (Mullerian) and mesonephric (Wolffian) ducts are present is dependent upon 2 fetal testicular hormones Mullerian duct inhibiting substance and Wolffian duct inducer substance. A and B only a, b and c Correct! No, the answer is E. In the fetus there is an indifferent stage of ductal development in which 2 pairs of genital or sex ducts are present mesonephric (Wolffian) and para-mesonephric (Mullerian) ducts. The fetal testis produces 3 hormones which are essential for development of the male duct system androgens, Mullerian duct inhibitor substance, and Wolffian duct inducer substance. Under the influence of these 3 hormones the mesonephric ducts persist and differentiate into the epididymis, ductus deferens, ejaculatory duct and seminal vesicles of the male. The paramesonephric ducts in the male degenerate except for a vestigial structure, the appendix of the testis. In the absence of the 3 testicular hormones the paramesonephric ducts contribute to the development of the uterine tubes and the uterus, while the mesonephric ducts degenerate except for several vestigial structures epoophoron, paroophoron, and the duct of Gartner. 4. Genital sex is independent of the presence or absence of testicular androgens is dependent on functional androgenic receptors in the target tissues undergoes an indifferent stage in which the external genitalia of both sexes is similar B and C only A, B and C Right! No, the answer is D. Genital sex is dependent upon the presence or absence of testicular androgens and the presence of functional androgenic receptors in the target tissues. Defects in the androgenic receptor mechanism in target tissues may lead to testicular feminization, cryptorchid testes, or hypospadias. The external genitalia of male and female embryos are similar during early genital sex development (indifferent stage). 5. Which of the following directly contribute (s) to the development of gonads the neural crest the somatopleuric mesenchyme the primordial germ cells B and C only none of the above Right! No, the answer is C. The gonads are derived from 3 sources the coelomic epithelium, the underlying mesenchyme, and the primordial germ cells. 6. Which of the following is (are) true of gonadal differentiation the gonadal ridge is produced by the proliferation of the cells of the germinal epithelium and the underlying mesenchyme the first indication of gonadal development is the presence of the primordial germ cells in the gonadal ridge the primary sex cords only form under the influence of a Y chromosome leading to the differentiation of a testis A and C only A, B and C Correct! No, the answer is A. Gonadal development is first indicated during when a thickened area of coelomic epithelium, the surface or germinal epithelium develops on the medial aspect of the urogenital ridge. Proliferation of cells of the germinal epithelium and the underlying mesenchyme produce a bulge on the medial side of each mesonephros known as the gonadal ridge. Whether the gonad develops into a testis or an ovary, the cells of the germinal epithelium grow into the underlying mesenchyme forming cord-like masses known as the primary sex cords (in which the primordial germ cells will eventually become embedded). The indifferent gonad consists of an outer cortex and an inner medulla. 7. The primordial germ cells are large primitive cells which are visible early in the 4th week among the endodermal cells of the yolk sac migrate via the dorsal mesentery to the gonadal ridge form from the germinal epithelium A and B only none of the above Right! No, the answer is D. The primordial germ cells are visible early in the 4th week among the endodermal cells of the yolk sac near the origin of the allantois. With the formation of the body folds, this part of the yolk sac is incorporated and form the hindgut. Later these cells migrate via the dorsal mesentery, and invade the underlying mesenchyme. They eventually become embedded in the primary sex cords. 8. The testis of the adult contains primary sex cords from the mesonephric tubules is surrounded by a dense fibrous tunica albuginea formed by the thickening of the mesenchyme underlying the coelomic epithelium contains Sertoli cells derived from the primordial germ cells contains seminiferous tubules derived from the primary sex cords Correct! No. The second and fourth foils are correct. In testicular development, the medulla persists and differentiates into the adult testis. The primary sex cords become separated from the coelomic epithelium by the condensation and proliferation of the mesenchyme to form a dense fibrous layer, the tunica albuginea. Subsequently, the sex cords form the seminiferous tubules the free ends of which anastomose to form the rete testis. The primordial germ cells in the seminiferous tubules form the spermatogonia while the Sertoli cells (which subserve a supportive function) are derived from the sex cord cells. 9. In the testis the connective tissue, fibrous septa and tunica albuginea form from the germinal epithelium the rete testis forms from the distal ends of the primary sex cords the Leydig (interstitial) cells form from the cells of the primary sex cords the seminiferous tubules become canalized at puberty under the influence of pituitary gonadotrophic hormones Correct! No. The second and fourth foils are correct. The connective tissue, fibrous septa, and tunica albuginea are derived from mesenchyme underlying the germinal epithelium. The rete testis forms from the distal (free) ends of the seminiferous tubules which are derived from the primary sex cords in the medulla.The Leydig (interstitial) cells produce testosterone in the adult and are derived from the mesenchyme. The seminiferous tubules remain as solid cords until puberty, when, as the result of stimulation by pituitary gonadotrophic hormones, the spermatogonia begin to proliferate, Sertoli cells increase in size, and the seminiferous tubules acquire a lumen. 10. In the developing ovary the primary sex cords degenerate secondary sex (cortical) cords form from the germinal epithelium and extend into the underlying mesenchyme primordial follicles consist of a central oogonium derived from primordial germ cells and surrounding follicular cells derived from the cortical cords no oogonia form postnatally Right! No. All foils are correct. During the development of the ovary, cortical differentiation is emphasized. The primary sex cords and a rete ovarii form, but soon degenerate. Secondary sex (cortical) cords form from the surface epithelium and extend into the underlying mesenchyme. Oogonia form from primordial germ cells, follicular cells from the cortical cords, and the ovarian strom from the mesenchyme. New oogonia are formed only prenatally. 11. The paramesonephric ducts form only in the female embryo form the appendix of the epididymis in the male contribute to the development of the urethra in the female commence as invaginations of the coelomic epithelium into the underlying mesenchyme on the lateral sides of the mesonephroi Right! No. Only the fourth foil is correct. The paramesonephric and mesonephric ducts form in both males and females. In the male, testicular hormones induce the degeneration of the paramesonephric ducts and the differentiation of the mesonephric ducts into the male duct system. The appendix of the epididymis is a remnant of aberrant mesonephric duct tissue which was not incorporated into the developing efferent ductules of the testis. The urethra in the female forms from the endoderm of the urogenital sinus. The paramesonephric ducts appear on the posterior abdominal wall of a 6 week embryo and commence as invaginations of the coelomic epithelium into the underlying mesenchyme on the lateral sides of the mesonephric kidneys. 12. In male embryos the prostate forms from the development of multiple endodermal outgrowths into the surrounding mesenchyme Cowper's glands form from endodermal outgrowths of the membranous portion of the urethra into the surrounding mesenchyme the prostatic utricle is homologous to the vagina the seminal colliculus is derived from the sinus tubercle and is homologous to the hymen in the female Correct! No. All foils are correct. The prostate and Cowper's (bulbourethral) glands form by a similar mechanism, the outpocketing of endoderm of the urethra into the surrounding mesenchyme. The stroma and smooth muscle of these glands is derived from the mesenchyme while the urethral endoderm is the source of the remainder of these glands. The prostatic utricle, a small diverticulum that opens on the seminal colliculus in the prostatic urethra, is probably homologous to the vagina. The seminal colliculus, a small elevation in the posterior wall of the prostatic urethra is the adult derivative of the sinus tubercle and is homologous to the hymen in the female. The sinus tubercle arises from the projection of the uterovaginal primordium (the fused portion of the paramesonephric ducts) into the dorsal wall of the urogenital sinus. 13. In the female embryo sexual development is dependent upon the presence of the ovaries the urethral and paraurethral glands (of Skene) are homologous to the prostate in the male and form from endodermal urethral buds which grow into the surrounding mesenchyme the vagina forms entirely from the uterovaginal primordium the greater vestibular glands (of Bartholin) are homologous with the bulbo-urethral glands of the male and form from outgrowths of the developing urethra (urogenital sinus) Right! No. The second and fourth foils are correct. In the female embryo, sexual development is dependent upon the absence of androgens and independent of ovarian development. The urethral and paraurethral glands are homologous to the male prostate gland and are formed in similar fashion. The vagina forms from 2 sources 1) the urogenital sinus is the source of the vaginal epithelium and 2) the uterovaginal primordium is the source for the fibromuscular wall of the vagina. The bulbourethral glands of the male and the greater vestibular glands of the female are homologous structures and develop in a similar method. 14. Which of the following is (are) true of the development of the female reproductive duct system in the development of the vagina, the contact of the uterovaginal primordium with the urogenital sinus induces the formation of sinovaginal bulbs which eventually fuse to form the vaginal plate the hymen forms from the uterovaginal primordium the broad ligament forms during the fusion of the paramesonephric ducts the uterus is primarily a pelvic organ in the newborn and the body of the uterus is large relative to the cervix Correct! No. The first and third foils are correct. Sinovaginal bulb formation is induced by the contact of the uterovaginal primordium with the urogenital sinus. The sinovaginal bulbs eventually fuse to form the vaginal plate which is canalized to form the vagina. The hymen forms from the sinus (Mullerian) tubercle and is homologous to the seminal colliculus. The fusion of the paramesonephric ducts brings together 2 peritoneal compartments of the pelvic cavity. 1) rectouterine pouch of Douglas and 2) the vesicouterine pouch. The uterus is primarily an abdominal organ in the newborn infant and its cervix is relatively large. 15. The uterus includes an epithelium and glands which are derived from the uterovaginal primordium is bounded on its lateral borders by the parametrium which forms between the layers of the broad ligament from adjacent mesenchyme includes an endometrial stroma and myometrium derived from adjacent mesenchyme is completely developed at birth Very good! No. The first three foils are correct. The uterine epithelium and glands are derived from the uterovaginal primordium while the endometrial stroma and the myometrium form from the adjacent mesenchyme. The parametrium forms on the sides of the uterus, between the layers of the broad ligament, and is derived from mesenchyme. During puberty the uterus undergoes a growth phase under the influence of the pituitary gonadotrophic hormones. 16. Which of the following statements is (are) true of the development of the external genitalia the phallus forms only in male embryos the labioscrotal swellings form the ventral aspect of the penis in the male and the labia minora in the female the urogenital folds form the scrotum in the male and the labia minora in the female under the influence of androgens, produced by the testes, the phallus elongates to form a penis, and the urogenital folds grow to the midline and fuse with each other to form the spongy urethra Right! No. Only the fourth foil is correct. The phallus forms in both male and female embryos during the indifferent stage of genital development. The urogenital folds fuse and form the ventral surface of the penis in the male and form the labia minora in the female. The labioscrotal folds fuse and form the scrotum in the male and the labia majora in the female. The development of the male external genitalia is dependent upon the presence of androgens secreted by the testes and on the presence of functional androgenic receptors in the target organs (for example, the labioscrotal swellings and the urogenital folds). 17. Which of the following statements is (are) true of the development of the external genitalia in the female the urogenital folds do not fuse except in the posterior region where they form the fourchette in the female the labioscrotal swellings fuse to form the anterior and posterior labial commissures and the mons pubis in the male the epithelium of the glans penis is derived from ectoderm in the female the vestibule of the vagina forms from ectoderm of the glandular plate Correct! No. The first three foils are correct. The frenulum of the labia minora (fourchette) forms posteriorly from the fusion of the urogenital folds. The labialscrotal folds fuse posteriorly to form the posterior labial commissure and anteriorly to form the anterior labial commissure and the mons pubis. The vestibule of the vagina, into which the urethra, the vagina and the ducts of the greater vestibular glands open is derived from the phallic portion of the urogenital sinus. In the male, an ectodermal ingrowth (glandular plate) forms at the tip of the glans. This ectodermal plate becomes continuous with the urethral groove and forms the epithelium of the glans penis (navicular fossa). 18. In the descent of the testes the gubernaculum demarcates the pathway of descent from the abdomen to the scrotum the processus vaginalis herniates through the abdominal wall carrying the layers of the wall with it the opening produced in the transversalis fascia by the processus vaginalis becomes the deep inguinal ring the opening in the internal oblique aponeurosis formed by the processus vaginalis becomes the superficial inguinal ring Very good! No. The first three foils are correct. The gubernaculum attaches the lower poles of the gonads to the labioscrotal folds and marks the line of descent of the processus vaginalis and the testis. The opening produced in the transversalis fascia by the processus vaginalis becomes the deep inguinal ring, and the opening in the external oblique aponeurosis forms the superficial inguinal ring. 19. The descent of the testes is complete by 28 weeks is entirely regulated by hormones (gonadotrophins and androgens) results in the ductus deferens crossing posterior to the ureter follows the gubernaculum and eventually passes posterior to the peritoneum and the processus vaginalis Very good! No. Only the fourth foil is correct. While the testes have descended from the posterior abdominal wall to the deep inguinal rings by 28 weeks, they require another month to traverse the inguinal canal and enter the scrotum. Descent from the posterior abdominal wall to the deep inguinal ring is caused by the differential growth of the gubernaculum compared to the body wall, while descent through the inguinal canal is regulated by hormones. The descent of the testes results in the ductus deferens crossing anterior to the ureter. The testes descend posterior to the peritoneum and processus vaginalis. 20. Which of the following statements is (are) true of the relationship of the fascial extensions of the abdominal wall and the coverings of the spermatic cord the extension of the transversalis fascia becomes the external spermatic fascia the external oblique aponeurosis forms the internal spermatic fascia the tunica vaginalis arises from the gubernaculum the internal oblique muscle gives rise to the cremasteric fascia and muscle Very good! No. Only the fourth foil is correct. The extension of the transversalis fascia becomes the internal spermatic fascia; the external oblique aponeurosis forms the external spermatic fascia; and the internal oblique muscle gives rise to the cremasteric fascia and muscle. The tunica vaginalis is the vestige of the processus vaginalis which remains after its stalk degenerates. 21. In the development of the ovary the gubernaculum attaches to the uterus near the attachment of the uterine tube the cranial part of the gubernaculum forms the ovarian ligament (round ligament of the ovary) the caudal part of the gubernaculum forms the round ligament of the uterus the round ligament of the uterus extends from the uterus through the inguinal canal Very good! No. All foils are correct. The ovary undergoes descent from the posterior abdominal wall to a point just inferior to the pelvic brim. The gubernaculum is divided into 2 parts, one cranial and one caudal which form the ovarian ligament (round ligament of the ovary) and the round ligament of the uterus. The processus vaginalis of the female may persist as the canal of Nuck. 22. Cryptorchidism is less frequent in premature infants than in full term infants results in a testis that is unable to produce mature sperms most frequently lies in the abdominal cavity may be caused by failure in normal hormonal production Very good! No. The second and fourth foils are correct. Cryptorchidism, or undescended testes occurs in 30% of premature males and in 3% of full term males. An undescended testis is unable to produce mature sperms. Although an undescended testis may be located in the abdomen or anywhere along the normal path of descent, it most frequently occurs in the inguinal canal. The cause is believed to be related to abnormal androgen production. 23. Which of the following statements is (are) true of congenital malformations concerning the descent of the testes ectopic testes are rare and may result from structural deviations in the gubernaculum congenital inguinal hernia may result from persistence of the processus vaginalis a hydrocele occurs when the abdominal end of the processus vaginalis remains open, but is too small to permit herniation of intestine cryptorchid testes discovered at birth require immediate surgical intervention Correct! No. The first three foils are correct. While cryptorchid testes are believed to be caused by hormonal alterations ectopic testes are probably caused by structural deviations in the gubernaculum. Ectopic testes occur rarely. Congenital inguinal hernia and hydrocele occur because of persistence of the processus vaginalis. In the case of the hernia, intestinal loops push into the opening while in the hydrocele the opening is only of sufficient diameter to permit peritoneal fluid to enter. 24. Which of the following is (are) true of penile malformations epispadias are more frequent than hypospadias hypospadias may be related to the production of androgens hypospadias are often associated with exstrophy of the bladder in epispadias the urethra opens on the dorsal surface of the penis Correct! No. The second and fourth foils are correct. Hypospadias occur in about 1/300 male births while epispadias occur in about 1/30,000 infants. In a hypospadia the urethra opens on the ventral surface of the penis instead of at the tip of the glans. Hypospadias may result from a failure in androgen production or the absence of androgens in the target organ resulting in failure of fusion of the urogenital folds and incomplete formation of the penile urethra. Epispadias often occur in association with exstrophy of the bladder. In an epispadia the urethra opens on the dorsal surface of the penis. 25. Which of the following is (are) true of uterovaginal malformations uterus didelphys results from failure of fusion of the inferior parts of the paramesonephric ducts bicornuate uterus results from doubling of only the superior portion of the body of the uterus a rudimentary uterine horn may develop if the growth of one paramesonephric duct is retarded absence of the sinovaginal bulbs may lead to absence of the vagina Very good! No, the answer is E. Uterovaginal malformations usually involve improper fusion of the paramesonephric ducts, incomplete development of the paramesonephric ducts, or doubling of part of the primordium. Absence of the vagina occurs in about 1/4,000 female births and results from the failure of the sinovaginal bulbs to form. Vaginal atresia and imperforate hypen are 2 other congenital malformations. They result from failure in the normal canalization of the vaginal plate. 26. Congenital virilizing hyperplasia is a form of female pseudohermaphroditism in which individuals are chromatin positive results from a block in the normal biosynthesis of cortisol is inherited as an autosomal recessive trait is characterized by the excessive production of androgens Very good! No. All foils are correct. Congenital virilizing hyperplasia is inherited as an autosomal recessive trait and results from a block in the normal biosynthesis of cortisol by the adrenal cortex. The result is an excessive production of ACTH (adrenocortico trophin) by the anterior pituitary. The high levels of ACTH stimulate the fetal adrenal cortex to produce excessive androgens which masculinize the female genitalia. These individuals have a 46,XX chromosomal constitution and are considered female pseudohermaphrodites. Administration of cortisol is the usual treatment. 27. Testicular feminization occurs in persons with an XY,46 chromosomal constitution occurs despite normal androgenic production occurs because of the insensitivity of the developing male duct system and genitalia to androgens occurs despite normal production of Mullerian duct inhibiting substance and Wolffian duct inducer substance Very good! No. All foils are correct. Persons with testicular feminization are phenotypically female despite the presence of a XY chromosomal constitution. The external genitalia are female but the vagina ends blindly, and the uterus and oviducts are rudimentary.The testes are usually ectopic, but produce normal levels of androgens. However, androgenic receptors in the target tissues are not sensitive to the presence of androgens. This results in the development of female ducts and genitalia. The presence of Mullerian duct inhibiting substance and Wolffian duct inducer substance results in the development of the male ducts (for example the ductus epididymis is usually present) and the rudimentary condition of the uterus and vagina. This condition is genetically determined and occurs in about 1/50,000 female births. The condition is usually diagnosed at the time of puberty when these "females" experience amenorrhea.