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1 Genital lsystem J. H. Lue Sexual differentiation is sequential process:.genetic (chromosomal) sex -- determined at fertilization.gonad sex -- is differentiated after 7th week.phenotypic sex -- under normal circumstances, chromosomal sex agrees with the phenotypic sex. 1

2 GONADS (i) mesothelium (mesodermal epithelium) (ii) mesenchyme (intermediate mesoderm);(i)+(ii) genital or gonad ridges (5 th week), (iii) primordial germ cells (PGC) endodermal cells of the yolk sac near the origin of allantois, migrate along the dorsal mesentery to the gonadal ridge at 6 th week 2

3 Primordial germ cells 3w primordial germ cells (PGC) endodermal cells of the yolk sac near the origin of allantois, migrate along the dorsal mesentery to the gonadal dlid ridge at 6 th week 3

4 Primordial germ cells 6w 6w primordial germ cells (PGC) endodermal cells of the yolk sac near the origin of allantois, migrate along the dorsal mesentery to the gonadal dlid ridge at 6 th week 4

5 INDIFFERENT GONADS.gonadal ridge (medial side of the mesonephros) proliferation of mesothelium and underlying mesenchyme.consists of : (i). Outer cortex + (ii). Inner medulla.in embryo with XY, medulla testis, with XX sex chromosome, cortex ovary 5

6 Development of testes.determines by the testis-determining factor (TDF) (SRY gene).in embryos with XY sex chromosome, PGC + medulla primitive sex cords testicular (seminiferous) or medullary cords.development of the tunica albuginea is a characteristic and diagnostic feature of testicular development.testicular cords seminiferous tubules, tubule recti, &rete testis 6

7 Development of testes.testicular cords seminiferous tubules, tubule recti,&rete testis mesenchyme surrounding the seminiferous interstitial cells (of Leydig), 8 th week begin to secret testosterone walls of seminiferous tubules, lumina begin to develop at puberty: (i). supporting or sustentacular cells of Sertoli ( germinal epithelium); (ii).spermatogonia ( PGC).rete testis persistent excretory mesonephric tubules (15-20) efferent ductules (ductuli efferentes).mesonephric or Wolffian duct epididymis, vas deferens, seminal vesicles and ejaculatory ducts 7

8 Development of ovaries in embryos with XX sex chromosome, primitive sex cords degenerate in 10th week, cortical cords formed; in 16th week, cortical cords primordial follicles:(i).oogonium ( PGC), (ii). Fl tt d ffollicular Flattened lli l cells ll ( mesothelium) ( th li ) germinal epithelium-- peritoneum no oogonia i form f postnatally t t ll in i full f ll term t humans h oogonium primary oocyte primary follicle mesenchyme mesenchyme surrounding the follicles ovarian stroma as the ovary separates from the regressing mesonephros, it becomes suspended by its own mesentery, mesovarium 8

9 Development of gonads TDF medullary cord No TDF cortical cord 9

10 Indifferent stage (6 th week) 7w 9w 7w 9w (a) Paramesonephric duct (Mullerian duct) funnel-like cranial portion coelomic cavity fused caudal portion uterine canal paramesonephric tubercle (b) Mesonephric duct (Wolffian duct) 10

11 Development of genital ducts 7w 8w *MIS ,000 daltons Testosterone a large dimeric glycoprotein external genitalia simulated formed by Sertoli cells of growth of penis, scrotum fetal and new born testis and prostate 11

12 Development of genital ducts 12

13 Development of male genital ducts.develops from the mesonephric ducts.mesonephric tubules efferent ductules.mesonephric ducts epididymis, ejaculatory ducts.mesonephric duct + surrounding mesenchyme ( muscular coat) ductus deferens. Out budding of tail of mesonephric duct seminal vesicle 6-week 6-week 13

14 Development of male genital ducts 4 th month.develops from the mesonephric ducts Testis descent.mesonephric tubules efferent ductules.mesonephric ducts epididymis, ejaculatory ducts.mesonephric duct + surrounding mesenchyme ( muscular coat) ductus deferens.out budding of tail of mesonephric duct seminal vesicle 14

15 Development of male genital glands Newborn out budding of tail of mesonephric duct seminal vesicle Primitive i i urogenital sinus (PUS) urethra prostate gland and bulbourethral gland 15

16 Development of prostate 11-week 11-week 16-week Prostate gland -- arise from the prostatic (endodermal) portion of the urethra and grow into the surrounding mesenchyme.endodermal cells glandular epithelium.mesenchyme dense stroma and smooth muscle 16

17 Development of bulbourethral glands Newborn bulbourethral gland -- arise from the spongy (endodermal) portion of the urethra.endodermal d d lcells glandular l.mesenchyme h dense stroma and epithelium smooth muscle 17

18 Development of female genital ducts 6-week 8-week 2 nd month Ovary descent develops from the paramesonephric p ducts (a). cranial vertical portion uterine tubes coelomic cavity (b). horizontal portion -- crosses the mesonephric duct (c). caudal vertical portion uterovaginal primordium (i). corpus, (ii). cervix of uterus, (iii). part of vagina 18

19 Development of female genital ducts 8-week 8w.formation of the broad ligaments:(i) (i). due to the fusion of the paramesonephric ducts. (ii). 2 mesenchymal peritoneal folds extend between the lateral ends of the fused ducts and the walls of the pelvis.side products: rectouterine pouch of Douglas & vesicouterine pouch 19

20 Development of female genital ducts 8w 20

21 Formation of the vagina 3 rd month Newborn 9 weeks.dual origins ()f (a). fused paramesonephric hi duct uterovaginal primordium i uterine canal and upper part of the vagina (b). uterovaginal primordium contact with the primitive urogenital sinus evaginates to form sinovaginal bulbs vagina plate canalized to form lower part of the vagina 21

22 Formation of the vagina 9 weeks 3 rd month Newborn 9 weeks 3 rd month.dual origins Newborn ()f (a). fused paramesonephric hi duct uterovaginal primordium i uterine canal and upper part of the vagina (b). uterovaginal primordium contact with the primitive urogenital sinus evaginates to form sinovaginal bulbs vagina plate canalized to form lower part of the vagina 22

23 Auxiliary genital glands in the female 12-week.urethral glands, paraurethral glands.greater vestibular glands (of Bartholin -- outgrowth from the urogenital sinus Newborn -- homologous to the bulbourethral glands 23

24 Anomaly development of female genital ducts Normal Double uterus and vagina Double uterus with single vagina Bicornuate uterus Bicornuate uterus with a rudimentary left horn Septate uterus Unicornuate uterus 24

25 Anomaly development of female genital ducts 25

26 mesenchyme cells around the urethral folds genital swellings (GS) (labioscrotal swelling) in male, GS scrotal swellings in female, GS labia majora Indifferent stage in the 4th week, mesenchyme cells from the primitive streak migrate around the cloacal membrane cloacal folds, cranial portion of the folds genital tubercle (GT) in the 6 week, cloacal membrane urogenital membrane & anal membrane; cloacal folds urogenital (urethral) folds & anal folds 26

27 Development of male external genitalia under influence of fandrogens ( ftl fetal testes), GT phallus urethral folds urethral groove, urethral plate penile urethra; glandular portion of penile urethra invaginate from the ectodermal cells fusion of scrotal swellings scrotal septum 27

28 Development of male external genitalia 10-week Newborn under influence of androgens ( fetal testes), GT phallus urethral folds urethral groove, urethral plate penile urethra; glandular portion of penile urethra invaginate from the ectodermal cells fusion of scrotal swellings scrotal septum 28

29 Anomalies 29

30 Development of female external genitalia under influence of estrogens, GT clitoris urethra folds labia minora; GS labia majora urogenital groove vestibule 30

31 Development of female external genitalia 5 months Newborn under influence of estrogens, GT clitoris urethra folds labia minora; GS labia majora urogenital groove vestibule 31

32 Sex abnormalities as reflected in the duct system and external genitalia hermaphroditism (intersexuality) true hermaphrodite pseudohermaphrodites male pseudohermaphrodites female pseudohermaphrodites Congenital virilizing adrenal hyperplasia Fusion of the labia majora Enlargement of the clitoris female pseudohermaphrodites 32

33 Descent of testis.2nd -- 7th month development.development of inguinal canal & formation of the vaginal process.the site of the inguinal canal in the fetus is first indicated by the gubernaculum (mesonephros degenerate, from inferior poles of gonad to the internal surface of the labioscrotal swelling).the processus vaginalis develops on each side ventral the processus vaginalis develops on each side ventral to the gubernaculum 33

34 Descent of testis.the processus vaginalis develops on each side ventral to the gubernaculum.the opening produced in the transversalis fascia by the processus vaginalis becomes the deep inguinal ring.the opening in the external oblique aponeurosis becomes the superficial inguinal ring.testis -- posterior abdominal wall -- deep inguinal rings -- inguinal canal -- superficial inguinal rings --scrotum 34

35 Possible factors that affect the descent of testis (a). the pelvis enlarges (b). the trunk of the embryo elongates (c). an increase in intrabdominal pressure (the growth of the abdominal viscera) (d). the hormone control, t l e.g. gonadotropins & androgens clinical evidence: by the administration of the gonadotropic hormones to treat the cryptorchidism (e). the exact role of gubernaculum is unknown (f). descent through h the inguinal i canal begins during week 28 and takes 2 to 3 days 35

36 Descent of ovary ovaries -- posterior abdominal wall -- inferior to the pelvic brim do not normally enter the inguinal canals, the processus vaginalis normally obliterates completely the gubernaculum attaches to the uterus ovarian ligament & round ligament of uterus 36

37 PGC TDF 37

38 GENITAL SYSTEM Dr. J.-H. Lue Embryology Sexual differentiation is sequential process:.genetic (chromosomal) sex -- determined at fertilization;.gonad sex -- is differentiated after 7th week;.phenotypic sex -- under normal circumstances, chromosomal sex agrees with the phenotypic sex. GONADS.derived from 3 sources (i) mesothelium (mesodermal epithelium) (ii) mesenchyme (intermediate mesoderm); (i)+(ii) genital or gonad ridges (5 th week), (iii) primordial germ cells (PGC) endodermal cells of the yolk sac near the origin of allantois, migrate along the dorsal mesentery to the gonadal ridge at 6 th week INDIFFERENT GONADS.gonadal ridge (medial side of the mesonephros) proliferation of mesothelium and underlying mesenchyme.consists of : (i). Outer cortex + (ii). Inner medulla.in embryo with XX sex chromosome, cortex ovary ; with XY, medulla testis TESTIS.determines by the testis-determining factor (TDF) (SRY gene).in embryos with XY sex chromosome, PGC + medulla primitive sex cords testicular (seminiferous) or medullary cords.testicular cords 1)seminiferous tubules; 2)tubule recti, &3)rete testis.mesenchyme surrounding the seminiferous interstitial cells (of Leidig), 8 th week begin to secret testosterone.walls of seminiferous tubules, lumina begin to develop at puberty: (i). supporting or sustentacular cells of Sertoli ( germinal epithelium) (mesothelium); (ii).spermatogonia ( PGC).rete testis persistent excretory (15-20) mesonephric tubules efferent ductules (ductuli efferentes).mesonephric ( Wolffian) duct 1)epididymis, 2)vas deferens, 3)seminal vesicles and 4)ejaculatory ducts 1

39 OVARY.in embryos with XX sex chromosome, primitive sex cords degenerate.in 10th week, cortical cords formed; in 16th week, cortical cords primordial follicles:(i).oogonium( PGC), (ii). flattened follicular cells ( mesothelium).germinal epithelium-- peritoneum.no oogonia form postnatally in full term humans.oogonium primary oocyte primary follicle.mesenchyme surrounding the follicles ovarian stroma.as the ovary separates from the regressing mesonephros, it becomes suspended by its own mesentery, mesovarium GENITAL DUCTS Indifferent stage (6 th week) (a). paramesonephric ducts (Mullerian duct): (i). funnel-like cranial portion coelomic cavity (ii). fused caudal portion uterine canal paramesonephric or Mullerian tubercle (b). mesonephric ducts (Wolffian duct) Differentiation of the duct system Influence of sex gland on further sex differentiation: Testis Mullerian inhibiting substance (MIS)* testosterone (Leydig s cells) (8 th week) paramesonephric ducts suppressed (7 th week) mesonephric ducts stimulated (efferent ductus ejaculatory duct) *MIS ,000 daltons a large dimeric glycoprotein formed by Sertoli cells of fetal and new born testis testosterone external genitalia simulated growth of penis, scrotum and prostate 2

40 Ovary estrogens (including maternal and placental sources) paramesonephric ducts stimulated (uterine tube, uterus, upper portion portion of vagina) external genitalia stimulated (labia, clitoris, lower of vagina) Genital ducts in the male.develops from the mesonephric ducts.mesonephric tubules efferent ductules.mesonephric ducts epididymis, vas deferens, ejaculatory ducts.outbudding of tail of mesonephric duct seminal vesicle.mesonephric duct + surrounding mesenchyme ( muscular coat) ductus deferens Auxiliary glands in the male prostate gland -- arise from the prostatic (endodermal) portion of the urethra and grow into the surrounding mesenchyme.endodermal cells glandular epithelium.mesenchyme dense stroma and smooth muscle bulbourethral gland -- outgrowths from the spongy part of the urethra.endodermal cells glandular epithelium.mesenchyme dense stroma and smooth muscle Genital ducts in the female.develops from the paramesonephric ducts: (a). cranial vertical portion uterine tubes coelomic cavity (b). horizontal portion -- crosses the mesonephric duct (c). caudal vertical portion uterovaginal primordium (i). corpus, (ii). cervix of uterus, (iii). part of vagina.two mesonephric (Wolffian) ducts regress Gartner s ducts.formation of the broad ligaments: (i). due to the fusion of the paramesonephric ducts.(ii). 2 mesenchymal peritoneal folds extend between the lateral ends of the fused ducts and the walls of the pelvis.side products: rectouterine pouch of Douglas & vesicouterine pouch 3

41 Formation of the vagina.dual origins: (a). fused paramesonephric duct uterovaginal primordium 1)uterine canal and 2)upper part of the vagina (b). uterovaginal primordium contact with the primitive urogenital sinus evaginates to form sinovaginal bulbs vagina plate canalized to form lower part of the vagina Auxiliary genital glands in the female.urethral glands paraurethral glands.greater vestibular glands (of Bartholin) -- outgrowth from the urogenital sinus -- homologous to the bulbourethral glands Anomalies.duplication and atresia of uterine canal (a). uterus didelphys, (b). bicornuate uterus, (c). bicornuate uterus with a rudimentary horn, (d). unicornuate uterus EXTERNAL GENITALIA Indifferent stage.in the 4th week, mesenchyme cells from the primitive streak migrate around the cloacal membrane cloacal folds, cranial portion of the folds genital tubercle (GT).in the 7 week, cloacal membrane 1)urogenital membrane &2)anal membrane cloacal folds 1)urogenital (urethral) folds &2)anal folds.mesenchyme cells around the urethral folds genital swellings (GS) (labioscrotal swelling) (i). in male, GS scrotal swellings (ii). in female, GS labia majora External genitalia in the male.under influence of androgens ( fetal testes), GT phallus.urethral folds urethral groove; urethral plate penile urethra glandular portion of penile urethra invaginate from the ectodermal cells.fusion of scrotal swellings scrotal septum Anormalies.hypospadias.epispadias.ectopia or exstrophy of the bladder 4

42 External genitalia in the female.under influence of estrogens.gt clitoris.urethra folds labia minora.gs labia majora.urogenital groove vestibule Sex abnormalities as reflected in the duct system and external genitalia.true hermaphrodite.pseudohermaphrodites (intersexuality).male pseudohermaphrodites.female pseudohermaphrodites Descent of testis (2nd -- 7th month development).development of inguinal canal & formation of the vaginal process.the site of the inguinal canal in the fetus is first indicated by the gubernaculum (mesonephros degenerate, from inferior poles of gonad to the internal surface of the labioscrotal swelling).the processus vaginalis develops on each side ventral to the gubernaculum.the opening produced in the transversalis fascia by the processus vaginalis becomes the deep inguinal ring.the opening in the external oblique aponeurosis becomes the superficial inguinal ring.testis posterior abdominal wall deep inguinal rings inguinal canal superficial inguinal rings scrotum possible factors that affect the descent of testis: (a). the pelvis enlarges (b). the trunk of the embryo elongates (c). an increase in intrabdominal pressure (the growth of the abdominal viscera) (d). the hormone control, e.g. gonadotropins & androgens clinical evidence: by the administration of the gonadotropic hormones to treat the cryptorchidism (e). the exact role of gubernaculum is unknown (f). descent through the inguinal canal begins during week 28 and takes 2 to 3 days Descent of ovary ovaries posterior abdominal wall inferior to the pelvic brim.do not normally enter the inguinal canals, the processus vaginalis normally obliterates completely.the gubernaculum attaches to the uterus ovarian ligament & round ligament of uterus 5

43 6

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