1. Development of Urinary & Male Genital System
M. Mansyur Romi

2. Introduction Urinary and genital systems are closely associated
Both develop from intermediate mesoderm
7th- 28th somite level (3rd week)
Nephrogenic mass (cord)
Dorsal side of coelom, each cord produces a bulge into the coelom called the urogenital ridge
Urinogenital Ridge
Form the urinary and genital structures
Nephrogenic tissue from 7-14th somite breaks up into segments called nephrotomes

3. Fig. 1 - Transverse section and dorsal view of an embryo (trilaminar) (ca. 21 days)
Transverse section of the three-layered embryo towards the end of the 3rd week of development.
1.Paraxial mesoderm 2.Intermediate mesoderm 3.Lateral mesoderm 4.Notochord 5.Amnion 6.Intraembryonic coelom 7.Endoderm 8.Ectoderm 9.Somatopleural (mesoderm and ectoderm) 10Splanchnopleural (mesoderm and endoderm) 11.Neural groove 12.Neural ridge

4. Kidney Development: Formation of 3 kidney systems
Pronephros (simplest & most primitive)
7-10 solid or tubular arranged cell groups in the cervical region (head kidney)
It is seen in the late 3rd wk, gone by the end of the 4th wk
Mesonephros (intermediate-more advanced)
Appear during regression of pronephros, 10-26th somite
It is transient, but serves as an excretory organ while the metanephros begins its development
It is seen at 24th day, dissapear by the 4th month
Metanephros (permanent kidney)
Begins to develop early in 5th wk, functions by the 11th wk

5. Pronephros (forekidney): transitory structure
1.Nephrogenic cord 2.Mesonephric duct (Wolff) 1+2.Mesonephros 3.Intestinal tube 4.Cloaca 5.Atrophying nephrotomes 6.Yolk sac (umbilical vesicle) 7.Allantois 8.Outflow of the mesonephric duct into the cloaca

6. Mesonephros Tubules develop from nephrogenic cord (NC)
Opens into the excretory/mesonephric duct
Gone by week 10 in females, in males some tubules persist & become vas deferens
Approximately 38 pairs of closed tubules
S shaped bend
Surrounds internal glomerulus
Mesonephric duct develops laterally from NC & extends from 8th somite to urinogenital sinus

7. Mesonephros: transitory kidney
1.Nephrogenic cord 2.Mesonephric duct 1+2.Mesonephros 3.Intestine 4.Cloaca 5.Atrophied nephrotome 6.Yolk sac (umbilical vesicle) 7.Allantois 8.Outflow of the mesonephric duct into the cloaca 9.Ureter bud (anlage)

8. Mesonephros enlargement point A
1.Neural tube 2.Notochord 3.Aorta dorsalis 4.Dorsal mesentery 5.Intestinal tube 6.Ectoderm 7.Somite 8.Inferior cardinal vein 9.Mesonephric duct (Wolffian duct) 10.Mesonephric tubule 11.Urogenital ridge

9. Mesonephros enlargement point A
1.Neural tube 2.Notochord 3.Aorta dorsalis 4.Dorsal mesentery 5.Intestinal tube 6.Ectoderm 7.Somite 8.Inferior cardinal vein 9.Mesonephric duct (Wolffian duct) 10.Mesonephric tubule 11.Urogenital ridge

10. Metanephros
Nephrons/tubules develop from nephrogenic mass (26th-28th somite level)
Located lateral to mesonephric duct
Internal dense layer which forms tubules/nephrons
Outer loose layer forms connective tissue capsule
Duct system derived from ureteric bud
Ureter, renal pelvis, calyces, collecting ducts
Ureteric bud elongates and makes contact with nephrogenic mass which surrounds bud like a cap
Tubules are closed (internal glomerulus)
Migrate from pelvis to abdomen as fetus grows
Blood supply from aorta changes as ascent occurs
Becomes functional in second ½ of pregnancy

11. Metanephric outflow
1.Cloaca 2.Ureter anlage 3.Metanephric blastema 2+3.Metanephros 4.Mesonephric duct (Wolffian duct) 5.Nephrogenic cord 4+5.Mesonephros

12. Renal ascent
Between the 6th – 9th wks the kidney ascend to a lumbar site just below the adrenal glands
When the kidney falls to ascend properly, its location becomes ectopic

14. Male Genital Development
Development of gonads
Development of genital ducts
Development of external genital

15. Origin Gonads – intermedial mesoderm of mesonephros
Primordial germ cells – endoderm of yolk sac
External genitalia – ectoderm and mesoderm

16. Indiferent stage Both sexes has same first stage coelomic epithelium
primary germ cords
primordial germ cells
mesonephric duct (Wollfian) and tubules
paramesonephric duct

17. Genital Development Formation of genital ridges
During the 5th week: primordial germ cells migrate from yolk sac to populate the mesenchyme of the posterior body wall near the 10th thoracic level
The arrival serves as the signal to form a pair of genital ridges, medial to the mesonephros
During the 6th week: the cells of ridges invade the mesenchyme to form primitive sex cords
A new pair of paramesonephric (mullerian) ducts begins to form lateral to the mesonephric ducts in both sexes

18. Genital Development

19. Genital Development Development of male genital structures
Under the influence of SRY (sex-determining region of Y) cells in medulla of primit. sex cords differentiate into Sertoli cells; otherwise (no SRY) into ovarian follicles
During the 7th week: Sertoli cells organize to form testis cords.
Direct contact between developing sertoli cells & primordial germ cells plays a key role in the proper development of male gametes

20. Male gonads
Y – chromosome: SRY (sex determining regionY) TDF (testes determining factor)
if produced  development of testis
usually from 7th week
if not produced  development of ovarium
usually from 12th week
„waiting period“

21. Genital Development

22. Development of testis
TDF stimulates proliferation of primary germ cord  medullary cords
origin of seminiferous tubules and rete testis
origin of Sertoli cells
intermedial mesenchyme
origin of Leydig cells
rest of coelomic epithelium changed to tunica albuginea

23. Seminiferous tubules Spermatogonia – from primordial germ cells
Sertoli cells
– surrounds spermatogonia
secrete anti-müllerian hormone (AMH) / Müllerian inhibiting hormone/substance (MIH/MIS)
inhibition of paramesonephric duct (Müllerian)
interstitial Leydig cells
produce testosteron from 8th week
no lumen till puberty

24. Genital ducts Connected medullar cords Mesonephric tubules
rete testis
Mesonephric tubules
Efferent ducts
Mesonephric duct (Wollfian)
Epididymal duct, ductus deferens, vesicular glands, ductus ejaculatorius
(ureter, pelvis, calices, collecting duct and tubules)
Paramesonephric duct (Müllerian) disappear

25. Genital Development Development of male genital structures
The sertoli cells begin to secrete mullerian-inhibiting substance (MIS), which causes mullerian ducts to regress rapidly 8th – 10th wks
During 9th – 10th wks Leydig cells differentiate from mesenchyme of the genital ridge in response to SRY protein; these produce testosteron
Between 8th – 12th wks testosteron stimulates mesonephric ducts to transform  vas deferens

27. Development of female genital structures
The seminal vesicles sprout from the distal mesonephric ducts
The prostate and bulbourethral glands develop from the urethra
Development of female genital structures
In the absence of SRY protein and Sertoli cells: MIS synthesis, Leydig cells diff. & androgen production do not occur
The mesonephric (wolffian) ducts degenerate, paramesonephric (mullerian) ducts give rise to the fallopian tubes, the uterus, the upper 2/3rd of the vagina.

28. Genital Development

29. Genital Development Development of external genitalia
The early development is similar in both sexes
In the 4th mth, the effects of dihydrotestosteron (DHT) on the male external genital become readily apparent
In the absence of dihydrotestosteron  female: the primitive perineum does not lengthen, and the labioscrotal and urethal folds do not fuse across the midline
The penile urethra is enclosed by the 14th wk

30. Genital Development

31. External genitalia indiferent stage genital tubercle urogenital folds
labioscrotal folds
male genital
penis
spongious urethra
scrotum

33. Gonadal descent
In both sexes the initial descent depends on a ligamentous cord: gubernaculum
Testes descend through inguinal canal down to the scrotum; ovaries remain within abdom.cvt
Testicles descend to internal inguinal ring by the 3rd mth and complete their descent into the scrotum by the 7th – 9th mth

34. Descensus of the testis
from thoracolumbal area to scrotum
AMH, testicular growth, elongation of body
gubernaculum – connective cord between testis and scrotum
from 26th week
mark of fetal maturity
cryptorchism vs. ectopic testis

35. Descensus of the testis

36. Spermatogenesis
Early in embryonic development, primordial germ cells enter the testes and differentiate into spermatogonia
Spermatogonia are diploid cells, each with 46 chromosomes (23 pairs) located around the periphery of the seminiferous tubules.
At puberty, hormones stimulate these cells to begin dividing by mitosis. Some remain at the periphery as spermatogonia.
Others become primary spermatocytes. Because they are produced by mitosis, primary spermatocytes are diploid and have 46 chromosomes.
Early in embryonic development, primordial germ cells enter the testes and differentiate into spermatogonia, immature cells that remain dormant until puberty. Spermatogonia are diploid cells, each with 46 chromosomes (23 pairs) located around the periphery of the seminiferous tubules.
At puberty, hormones stimulate these cells to begin dividing by mitosis. Some of the daughter cells produced by mitosis remain at the periphery as spermatogonia. Others are pushed toward the lumen, undergo some changes, and become primary spermatocytes. Because they are produced by mitosis, primary spermatocytes, like spermatogonia, are diploid and have 46 chromosomes.

37. Spermatogenesis
Each primary spermatocytes goes through the first meiotic division, meiosis I, to produce two secondary spermatocytes, each with 23 chromosomes (haploid). Just prior to this division, the genetic material is replicated . During meiosis I, one chromosome, goes to each secondary spermatocyte.
In the second meiotic division, meiosis II, each secondary spermatocyte divides to produce two spermatids. There is no replication of genetic material in this division, but a single-stranded chromatid goes to each cell.
As a result of the two meiotic divisions, each primary spermatocyte produces four spermatids, each spermatid has 23 chromosomes (haploid), one from each pair in the original primary spermatocyte.
Each primary spermatocytes goes through the first meiotic division, meiosis I, to produce two secondary spermatocytes, each with 23 chromosomes (haploid). Just prior to this division, the genetic material is replicated so that each chromosome consists of two strands, called chromatids, that are joined by a centromere.
During meiosis I, one chromosome, consisting of two chromatids, goes to each secondary spermatocyte. In the second meiotic division, meiosis II, each secondary spermatocyte divides to produce two spermatids. There is no replication of genetic material in this division, but the centromere divides so that a single-stranded chromatid goes to each cell. As a result of the two meiotic divisions, each primary spermatocyte produces four spermatids.
During spermatogenesis there are two cellular divisions, but only one replication of DNA so that each spermatid has 23 chromosomes (haploid), one from each pair in the original primary spermatocyte. Each successive stage in spermatogenesis is pushed toward the center of the tubule so that the more immature cells are at the periphery and the more differentiated cells are nearer the center.

38. Spermatogenesis

39. Spermatogenesis
The final step in the development the spermatids formed from spermatogenesis become mature spermatozoa, or sperm.
The mature sperm cell has a head, midpiece, and tail.
The head, also called the nuclear region, contains the 23 chromosomes surrounded by a nuclear membrane. The tip of the head is covered by an acrosome, which contains enzymes that help the sperm penetrate the female gamete.
The midpiece, metabolic region, contains mitochondria that provide adenosine triphosphate (ATP).
The tail, locomotor region, uses a typical flagellum for locomotion.
The final step in the development of sperm is called spermiogenesis. In this process, the spermatids formed from spermatogenesis become mature spermatozoa, or sperm.
The mature sperm cell has a head, midpiece, and tail. The head, also called the nuclear region, contains the 23 chromosomes surrounded by a nuclear membrane. The tip of the head is covered by an acrosome, which contains enzymes that help the sperm penetrate the female gamete. The midpiece, metabolic region, contains mitochondria that provide adenosine triphosphate (ATP). The tail, locomotor region, uses a typical flagellum for locomotion.
The sperm are released into the lumen of the seminiferous tubule and leave the testes. They then enter the epididymis where they undergo their final maturation and become capable of fertilizing a female gamete.
Sperm production begins at puberty and continues throughout the life of a male. The entire process, beginning with a primary spermatocyte, takes about 74 days. After ejaculation, the sperm can live for about 48 hours in the female reproductive tract.

41. Spermatogenesis
The sperm are released into the lumen of the seminiferous tubule and leave the testes. They then enter the epididymis where they undergo their final maturation and become capable of fertilizing a female gamete.
Sperm production begins at puberty and continues throughout the life of a male.
The entire process, beginning with a primary spermatocyte, takes about 74 days. After ejaculation, the sperm can live for about 48 hours in the female reproductive tract.

42. Spermiogenesis: Spermatids to Sperm

43. Pembuahan / fertilisasi / konsepsi