1. Embryology of urogenital system

2. Learning outcomes
Define mesoderm and outline the formation of mesonephric and paramesonephric ducts.
Describe the embryogenesis of male reproductive organs & external genitalia.
Discuss the development of female reproductive organs & external genitalia.
List the congenital anomalies associated with urogenital development.

3. Basic embryology

4. Blastocyst formation
After fertilization the zygote undergoes rapid mitotic cell division called cleavage divisions.
Cleavage produces a solid sphere of cells, still surrounded by zona pellucida – morulla.
At 4 to 5 days, cells have developed into a hollow ball of cells – blastocyst.

5. Bilaminar germ disc
As early of 2 weeks, inner cell mass differentiate into two layers of cells called bilaminar germ disc:
- Epiblast (columnar cells) Hypoblast (cuboidal cells).
Epiblast gives rise to
- Primary ectoderm
- Amniotic membrane: amnioblast.
Hypoblast gives rise to
- Primary endoderm
- Extraembryonic endoderm→exocoelomic membrane→primary yolk sac.

6. Bilaminar germ disc

7. Trilaminar germ disc
In between the yolk sac and the amniotic cavity is the embryonic disc, which gives rise to the primary germ layers:
Endoderm
Mesoderm
Ectoderm
Ectoderm: Epiblast cells form the ectoderm.
Mesoderm: Intraembryonic mesoderm.
Endoderm: Hypoblast cells are replaced by epiblast cells
Trilaminar germ disc: endoderm + mesoderm + ectoderm.

8. Trilaminar germ disc

9. Trilaminar germ disc

10. Ectoderm -Derivatives
Differentiation of ectoderm: from 18th–19th days:
Neural plate: neuro-epithelium(neural ectoderm), neural fold, neural groove, neural tube: →CNS
Neural crest (mesoectoderm): two lines of cell cords→ganglion.

11. Mesoderm Differentiation of mesoderm: 17th day. Paraxial mesoderm:
-Somite:20thday, 3 pairs/per day, pairs by the end of 5th weeks.
-sclerotome:→bone, cartilage,
-myotome:→skeletal muscle,
-dermatome:dermis and hypodermis.

12. Mesoderm Intermediate mesoderm: - kidney and reproductive organs.
Lateral plate mesoderm:
- Intraembryonic coelom: →body cavity.
- Somatic or parietal mesoderm: →muscle, connective tissue, parietal layer of pleura, peritoneum and pericardium.
-Splanchnic or visceral mesoderm: →muscle, connective tissue of digestive tract, visceral layer of pleura, peritoneum and pericardium.
Mesenchyme: Cardiovascular and lymphatics.

13. Development of urogenital system

14. Development of urogenital system
Development of the urinary and reproductive systems are closely associated.
Both systems develop from two longitudinal ridges of mesoderm which run down the entire length of the dorsal body wall. These ridges are called urogenital ridges.
The medial region of this ridge differentiates into the genital ridge where the gonads develop.
The urogenital ridge consists of the mesonephros and the gonad.

15. Urinary system
The urinary system develops in the urogenital ridge as three successive sets of excretory organs - the pronephros, mesonephronos, and metanephros.
The pronephros forms first and quickly disappears.
The mesonephros develops and disappears with the exception of its duct, the mesonephric duct which form the male reproductive duct system.
A few mesonephric tubules remain as efferent ductules in the male and vestigial remnants in the female.

16. Urinary system
The metanephros is the third and final excretory organ. It becomes the permanent kidney.
The metanephros develops from two sources: the ureteric bud which is a diverticulum from the mesonephric duct and metanephrogenic mass of mesoderm,a mass of mesoderm that condenses around the ureteric bud during development.
The ureteric bud further differentiates into the ureter, urinary pelvis, major and minor calyces and collecting tubules.
The metanephrogenic mass of mesoderm differentiates into nephron units (proximal and distal convoluted tubules, loops of Henle, and Bowman's capsule).

17. The Genital system (Reproductive organs)

18. Development of gonads (testis or ovary)
The gonads begin to develop during the fifth week in the genital ridge.
The gonads are first undifferentiated and have only a cortex and a medulla.
The type of gonad to be developed, female or male, is determined at fertilization.
- In embryos with an XX chromosome complex, the cortex normally differentiates into an ovary, and the medulla regresses.
- In embryos with an XY complex, the medulla differentiates into a testis and the cortex regresses.

19. Development of gonads
On either side of the root of the dorsal mesentery is the genital ridge which has the condensation of intermediate mesoderm covered by coelomic epithelium.
Coelomic epithelium becomes germinal epithelium.
By the 6th week primordial germ cells migrate from the wall of the yolk sac into the genital ridge.

20. Development of gonads

21. Development of gonads

22. Development of gonads
Sex cords develop from the germinal epithelium. Sex cords grow into the mesenchyme of the genital ridge in both sexes. Further development differs in two sexes.
Development of ovary
Absence of Y chromosome and presence of 2 X chromosome - lead to the development of ovary.
Sex cords break up into small clusters each of which surrounds a germ cell forming a primordial follicle.
Medulla & Cortex are differentiated. Follicles occupy the cortex.
Division of germ cell & formation of primordial follicle occur before birth.

23. Development of gonads

24. Development of gonads

25. Development of gonads

26. Development of testis
Directed by the testes development factor of Y chromosome.
Development of tunica albuginea separates the germinal epithelium from sex cords.
Primordial germ cells come to lie in the sex cords.
Sex cords canalize to form seminiferous tubules and the rete testis.
Some of the mesenchymal cells between the seminiferous tubules differentiate into Leydig cells, producing teststerone about the 8th week.
Some mesenchymal cells in the seminiferous tubules differetiate into Sertoli cells.
Testosterone promotes development of male genitalia.
Mullerian inhibitory hormone from the Sertoli cells suppress the development of paramesonephric duct.

27. Descent of testis
Testis descends from the lumbar region to the scrotum.
3rd month --from loin to pelvis.
4th –7th month lies at the deep inguinal ring.
7th month –traversing the inguinal canal.
8th month-- at the superficial inguinal ring.
9th month—to the upper part of the scrotum.
Reaches the bottom of the scrotum at or soon after birth.
Testis descends to cooler atmosphere for the normal functioning.

28. Descent of testis

29. Congenital anomalies of testis
Undescended testis may lie anywhere in the pelvis or abdomen, may become malignant if left.
Cryptorchidism is the absence of testis in the scrotum.
Ectopic testis- abnormal position of the testis.

30. Development of reproductive organs

31. Development of reproductive organs
Two pairs of genital ducts develop in both sexes:
- Mesonephric (Wolffian) duct.
- Paramesonephric (Mullerian) duct.

32. Development of female reproductive organs
Paramesonephric ducts develop next to mesonephric duct in the posterior body wall.
The caudal ends of paramesonephric ducts fuse to form a uterovaginal canal in both sexes. The cranial ends of the ducts open into the future peritoneal cavity.
In female embryos, mesonephric ducts regress and paramesonephric ducts develop into uterine tubes, uterus, and upper vagina.

33. Development of uterus & uterine tube
The paired paramesonephric ducts fuse in the midline forming the single body of the uterus.
The paramesonephric ducts remain separate laterally where they form the uterine tubes.

34. Development of vagina
Embryonic origin of the vagina has been a historically hotly debated issue with several different contributions. One view:
Vaginal cords proliferate from the lower end of uterovaginal canal [mesodermal].
Sinovaginal bulbs from Mullerian tubercle [endodermal].
Vaginal cords and the sinovaginal bulbs join to form the vaginal plate.
Vaginal plate canalises to form vagina.Near its lower end a thin partition remain for some time as hymen.
So upper part is mesodermal & lower part is endodermal in origin.
Current molecular studies show the whole vagina is derived from the Müllerian duct with bone morphogenic protein 4 (BMP4) reshaping the intermediate mesoderm-derived Müllerian duct into the vaginal primordium.

35. Development of female reproductive organs

36. Development of male reproductive organs
In male, the mesonephric duct system remains to form efferent ductules, epididymis, vas deferens and ejaculatory duct.
The seminal vesicle develops as a diverticulum from the developing vas.
The paramesonephric system regresses except the prostatic utricle on the seminal colliculus and appendix of testis.
In female, most of the mesonephric duct disappear.It gives rise to –ureter, trigone of the bladder, collecting part of the kidney, epöhoron and paröphoron.

37. Congenital anomalies of uterus & uterine tube

38. Development of external genitalia

39. Development of external genitalia
Genital tubercle develops ventral to the cloacal membrane - 4th week.
Genital tubercle elongates to form a phallus with a urethral groove on its ventral surface.
Formation of bilateral urogenital folds & labio scrotal swellings.

40. Development of external genitalia

41. Development of external genitalia
In male:
Testosterone promotes elongation of phallus into penis.
Urethral or urogenital folds fuse to form penile urethra.
Labio scrotal swellings fuse to form scrotum.

42. Development of external genitalia
In female:
Genital tubercle is small,gives rise to – clitoris.
Urogenital folds & labio scrotal swellings do not fuse in the midline & develops into labia minora & majora.

43. Development of external genitalia

44. Congenital anomaly - Hypospadiasis
Failure of the fusion of Urethral or urogenital folds ventrally lead to hypospadias (urethra opening ventrally)

45. Congenital anomaly - Epispadiasis
Failure of the fusion of Urethral or urogenital folds dorsally lead to epispadiasis (urethra opening dorsally)

46. Ambiguous genitalia

47. Ambiguous genitalia
Ambiguous genitalia and Intersexuality: Birth defect where the outer genitals do not have the typical appearance of either a male or a female.
Ambiguous genitalia in genetic females (babies with XX chromosomes) has the following features:
An enlarged clitoris that has the appearance of a small penis.
The urethral opening can be anywhere along, above, or below the surface of the clitoris.
The labia may be fused, resembling a scrotum.
The infant may be thought to be a male with undescended testicles.
Sometimes a lump of tissue is felt within the fused labia, further making it look like a scrotum with testicles.

48. Ambiguous genitalia
Ambiguous genitalia in a genetic male ( XY chromosome), include the following features:
A small penis (less than 2-3 centimeters) that resemble an enlarged clitoris (the clitoris of a newborn female is normally enlarged at birth).
The urethral opening may be anywhere along, above, or below the penis; it can be placed as low as on the peritoneum, further making the infant appear to be female.
Small scrotum with some degree of separation, resembling labia.
Undescended testicles commonly accompany ambiguous genitalia.

49. Summary

50. Development of gonads
On either side of the root of the dorsal mesentery is the genital ridge which has the condensation of intermediate mesoderm covered by coelomic epithelium.
Coelomic epithelium becomes germinal epithelium.
By the 6th week primordial germ cells migrate from the wall of the yolk sac into the genital ridge.

52. Development of reproductive organs
Male - mesonephric duct (Wolffian) forms efferent ductules, epididymis, vas deferens and ejaculatory duct.
Female - paramesonephric duct (Mullerian) develops into uterine tubes, uterus, and upper vagina.

53. Development of external genitalia
During development, initially the external genitalia are identical in both sexes.
External genitalia develops from genital tubercle (phallus), urethral fold and labioscrotal fold.
Male:
- Genital tubercle becomes the penis.
- Urethral folds fuse to become urethra.
- Fused labioscrotal fold becomes scrotum.
Female:
- Genital tubercle becomes the clitoris.
- Urethral folds remain separated as the labia minora.
- Unfused labioscrotal fold becomes labia majora.

54. Any Questions ?

55. Thank you