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Home , Gonadal ridge, Nephrotome, Pronephric duct

Anhui Medical University

Development of the Urogenital System

Lyu Zhengmei Department of Histology and Anhui Medical University Anhui Medical University

 ORIGINS---- ---paraxial mesoderm: somite --- urinary and genital system ---lateral mesoderm

paraxial neural intermediate mesoderm groove mesoderm

notochord lateral mesoderm Anhui Medical University Part I Introduction

The 【】※ origins of origins of urogenital urogenital system system?? Anhui Medical University differentiation of intermediate mesoderm

•intermediate mesoderm Nephrotome urogenital ridge mesonephric ridge， Anhui Medical University

1.Formation of nephrotome

Nephrotome: The cephalic portion of intermediate mesoderm becomes segmented,

which forms pronephric system and degenerates early. 4 weeks Anhui Medical University  intermediate 2.Nephrogenic cord mesoderm Its caudal part gradually isolated from somites, forming two longitudinal elevation along the posterior wall of abdominal cavity

Nephrogenic cord

urogenital ridge Anhui Medical University 3. Urogenital ridge

Mesonephric ridge:

The outside part of the urogenital ridge giving rise to the urinary system

Gonadal ridge:

the innerside part giving rise to the genital system Anhui Medical University Part II Development of Urinary system Three sets of occur in developmnet ( 1) (2) (3) metanephros

Development of Bladder and urethra

Congenital anomalies of the urinary system Anhui Medical University Three sets of kidney systems 1 Pronephros

•development begins early in fourth week

•nonfunctional as a kidney

•pronephros attached to pronephric ducts, these ducts are utilized by next set of kidney •pronephric tubule Pronephros degenerate in the end of fourth week Anhui Medical University

2. Mesonephros: •Mesonephros begins development in mesonephric ridge late in the fourth week

•lie caudal to pronephros

•large and elongated, functional interim, during early embryonic life Anhui Medical University •mesonephros consists of glomeruli and which open laterally into , a continuation of the

•mesonephric duct opens into cloaca

Mesonephric •Most of the mesonephros tubule Mesonephric degenerates duct •But tubules and ducts have derivatives in adult male reproductive structures Anhui Medical University 3. Metanephros

•permanent kidneys •begin development early fifth week

•develop from the

and the metanephrogenic tissue •Function begins at 11th-12th week •urine produced and released into amniotic fluid Anhui Medical University (1)ureteric bud The ureteric bud is formed from an outgrowth of the mesonephric duct near the cloaca Developing into the ureter, renal pelvis, major and minor calyces and collecting tubules Anhui Medical University

Human E35-37, epithelia bud at end

of mesonephric duct -----ureteric bud Metanephrogenic ureteric bud induced by blastema metanephric to ureteric differentiate into collecting tubules, bud calyces, renal pelvis, ureter minor calyces

ureteric bud associated with Major calyces metanephric mesenchyme nephron Anhui Medical University (2)Metanephrogenic tissue The metanephrogenic tissue formed from the caudal portion of the intermediate mass of mesonephric ridge , and surrounds the end of the ureteric bud. Anhui Medical University Development of nephrons Metanephric vesicles formed in metanephrogenic tissue, which elongate to form S-shaped tubules  Capillaries grow into and form glomeruli

. Renal capsule and renal tubule

Connect with arched collecting tubules Anhui Medical University 4 Ascent of Kidneys The kidney, initially in the pelvic region, with their hila pointed anteriorly eventually come to lie in a retroperitoneal position at the level of lumbar 1(L1) by the ninth week Function of the permanent kidney begins at month 3rd. Anhui Medical University

Causes of ascent of kidney:

As the pelvis and abdomen grow, the kidneys slowly move upward. By the seventh week, the hilum points medially and the kidneys are located in the abdomen.

caused by diminution of body curvature and by growth of the body in the lumbar and sacral regions Anhui Medical University 4. Development of Bladder and urethra

Cloaca: Just superior to the cloaca membrane, the primitive gut forms an expansion

The urogenital sinus is formed by the division of the cloaca by the uro-rectal septum cloaca Anhui Medical University

The urogenital sinus is formed by the division of the cloaca by the uro-rectal septum

Mesonephric duct

Coronal plane view

Ureteric bud urogenital sinus

Uro-rectal septum Sagittal plane view hindgut Anhui Medical University urogenital sinus ( 1) the cranial portion, continuous with the allantois and forms the bladder proper. (2) the pelvic part of the sinus forms the prostatic urethra and part of the in females. (3)the caudal portion, forms the penile urethra in males and the vestibule in females.

Uro-rectal septum rectum Anhui Medical University allantois the cranial female portion

the pelvic urethra and vagina part

Uro-rectal septum

vestibule the caudal portion Anhui Medical University

the cranial portion allantois

male

urethra (prostatic and membranous) the pelvic part

penile urethra the caudal portion Anhui Medical University Part III Congenital anomalies of the urinary system 1. polycystic kidney A failure in the connection between the nephron and the collecting system Kidney contains many cysts, and failure in renal function Anhui Medical University

2. ectopic kidney ( pelvic kidney)

Ascent, arterial fork, fail to do so. Remaining in the pelvis. Anhui Medical University 3、horseshoe 4、double ureter

The horseshoe kidney is a form of ectopic kidney in which the poles of the two kidneys fuse in the pelvic cavity prior to ascending. This leads to a large U-shaped kidney which is unable to ascend to the level of loin(L1) because it is blocked by the inferior mesenteric artery Anhui Medical University

5、urachal fistula 6、extrophy of bladder

Lack of mesodermal migration into the region between the umbilicus and genital The lumen of the allantois persists tubercle Anhui Medical University

Three sets of kidney occur Summary in embryo developmnet (1)pronephros (2) mesonephros (3) metanephros

Two origins of metanephros: ureteric bud and metanephric tissue

Development of Bladder and urethra Cloaca Urogenital sinus Anhui Medical University

PartⅣ Development of 1. Development of gonads (1) sexual indifferentiation of gonad (2) development of testis (3) development of ovary (4) descent of testis and ovary

2. Development and of genital ducts (1) indifferent stage (2) differentiation of genital ducts in female (3) differentiation of genital ducts in male

3.Congenital anomalies of the genital system Anhui Medical University 1.Development of gonads (1) Gonadal ridge----- sexual indifferentiation of gonad

Although the sex of an infant is determind at fertilization, it is not until the seventh week that the gonads can be differentiated Anhui Medical University gonadal ridge •Gonadal ridge In the fifth week ,The urogenital ridge is divided into mesonephric ridge and gonadal ridge.

• Primary

By the sixth week, the epithelium of mesonephric gonadal ridge has developed primary ridge sex cord.

the fifth week Anhui Medical University • Primordial (PGC)：

.originate from the endoderm Gonadial around the . ridge .migrate along the dorsal mesentery of the gut, appear in the genital ridges in the sixth week. Mesoneph- ric ridge influence development of gonad

Primordial germ cell

in the fourth week of life in the sixth week of life Dissection of an embryo Anhui Medical University

Summary----- The gonad are derived from three sources: • The coelomic epithelium  The underlying mesenchyme • The primordial germ cells Anhui Medical University

(2) Development of testis

One of the critical events in sexual differentiation occurs in the sixth week.

SRY gene:

Embryos which contain the Y chromosome have a specific gene known as SRY(sex determining region of the Y). This gene code a testes determining factor (TDF) which determines the formation of testes.

TDF is expressed in the primordial germ cells . Anhui Medical University

TDF induces the testicular cord to condense and extend into the medulla of the indifferent gonad: branch and anastomose the seminiferous cords are separated by mesenchyme During further development, a layer of fibrous connective tissue which separates the sex cords (seminiferous cords) from the surface epithelium, tunica albuginea

This mesenchyme will go on to produce Leydig cells Anhui Medical University Leydig cells produce testosterone which maintains the presence of these mesonephric ducts and the tubules of the mesonephros  The seminiferous cords are made up of a large number of Sertoli cells which secretes anti-Müllerian hormone The seminiferous cords remain solid until puberty , at which time a lumen develops and they become the seminiferous tubule Anhui Medical University Summary in the sixth week primordial germ cells migrate into gonad ridge------indifferent stage of gonad

Induced by TDF, primary sex cords differentiate into Seminiferous cord in the seventh week only two type cells: Sertoli cells and spermatogonium, Seminiferous tubules did not start to grow until puberty

Sertoli cells which secretes anti-Müllerian hormone Leydig cells produce androgen

in the eighth week proliferating of mesenchymal cells under mesothelium form tunica albuginea Descent of testis into the scrotum. Anhui Medical University

(3) Development of Ovaries

In the absence of SRY, a female embryo will develop.

Ovaries are not identifiable until the tenth week. In a female embryo, the primitive sex cords (medullary cords) degenerate.

The secondary sex cords is formed that extend from the surface epithelium to the mesenchyme. Anhui Medical University

coelomic epithelium cortical sex cords

cell mass primordial germ cells cortical sex cords

Oogonia follicular cell

1st meiotic division primary oocytes

primordial follicles

Development of ovary Anhui Medical University

OUTLINE of gonadal development Urogenital ridge

gonadial ridge mesonephric ridge Anhui Medical University (4) descent of testis and ovary

Neither the testes nor the ovaries remain located in the body at their place of origin The testes descend into the scrotum, following the course of the  The ovaries descend into the pelvis Anhui Medical University Descent of testis

Gubernaculum derive from mesoderm Cranial end connected with caudal part of gonad Caudal end connected with labioscrotal  Embryo growth leads to a relatively shorter of gubernaculum Anhui Medical University Process of Testicular descent

 Dropped through the inguinal canals , testes enter the scrotum Peritonaeum form processus vaginalis the channel between processus vaginalis and abdominal cavity closed , tunica vaginalis is formed.

During the first 3 month after birth, most of them descend into the scrotum Anhui Medical University

• Statistics for Testes Descent Data from a recent study of male human fetal (between 10 and 35 weeks) gonad position:  10 to 23 weeks - (9.45%) had migrated from the abdomen and were situated in the inguinal canal  24 to 26 weeks - (57.9%) had migrated from the abdomen  27 to 29 weeks - (16.7%) had not descended to the scrotum  A second study showed that from 33 weeks fetal testes had descended to the scrotum and that between 33 to 40 weeks (term) both testes have normally descended to the scrotum. Failure of descent (cryptorchidism) either unilateral or bilateral testicular descent, occurring in up to 30% premature and 3-4% term males. Anhui Medical University

2. Development and sexual differentiation of genital ducts

indifferent stage

different stage Anhui Medical University (1)indifferent stage

(male) Degeneration of female Mesonephric tubules

Rete testis

Seminiferous tubules tunica albuginea

mesonephric ducts

Sixth week of human embryo Anhui Medical University (2)Differentiation of genital ducts in male Testosterone secreted by Leydig cells. This maintains the presence of these mesonephric ducts . The tubules of the mesonephros hook up to the rete testis. This results in formation of the ductuli efferents. These tubules are continuous with the mesonephric duct, which forms the epididymis.

antimüllerian hormone secreted by Sertoli cells which inhibits the paramesonephric ducts which then degenerate around the ninth week of development. Anhui Medical University

after descent of testis mesonephric tubules →efferent ductules ejaculatory Seminal vesicle mesonephric ducts →epididymis ductus deferens ejaculatory ductus deferens

Seminiferous tubules efferent ductules

Epididymis Anhui Medical University (3)Differentiation of genital ducts in female Paramesonephric duct(Müllerian)

--arises as a longitudinal invagination of the epithelium on the surface of the mesonephric ridge

-- the cranial end openings into the abdominal cavity, the caudal tip projects into the posterior wall of the urogenital sinus sinus tubercle cranial—run lateral to the mesonephric duct

median—cross ventral to the mesonephric duct, approach each other

lower—run inboard to the mesonephric duct Anhui Medical University Differentiation of Paramesonephric duct lack of testosterone no mullerian inhibiting substance Degeneration of mesonephric ducts Paramesonephric duct

The cranial parts uterine tubes

The caudal fuse portion Mesonephric uterus, upper vagina ducts sinus tubercle a solid vaginal plate Anhui Medical University 4.congenital anomalies of the genital system

①Cryptorchidism cryptorchid testes are usually in the inguinal canal. They fail to mature and sterility is common.

②Congenital inguinal hernia

Intestine loops decend into the scrotum ③Hermaphroditism discrepancy between gonad and external genitalia Anhui Medical University

④Abnormal development of the uterus Double uterus: the Paramesonephric duct’s caudal portion failure in fusion, may associated with a double vagina

Bicornuate uterus: the Paramesonephric duct’s upper caudal portion failure in fusion Anhui Medical University SUMMARY OF THE CHAPTER The male and female reproductive systems develop initially "indifferently", it is the product of the Y chromosome SRY gene that makes the "difference".

The primitive sex cords degenerate, and a secondary group of cortical sex cords is formed in ovaries development. Primary oocytes arrest their development at the 1st meiotic division. Sexual diffenrentiation of genital ducts are controlled by AMH and androgen. At indifferent stage, there are two sets of ducts: paranesonephric ducts , mesonephric ducts and tubules. Anhui Medical University

 Mesonephric duct (Wolffian Duct) majority of male internal genital tract paramesonephric duct(Müllerian Duct) majority of female internal genital tract

The changes of mesonephric/paramesonephric duct are one of the first male/female differences that occur in development, while external genitaila remain indeterminate in appearance for quite a while. Anhui Medical University

 There are many different issues to consider in  Importantly its sex chromosome dependence, the development of the genital system: late embryonic/fetal differential development, complex morphogenic changes, long time-course, hormonal sensitivity and hormonal influences

 So make it a system prone to many different abnormalities Anhui Medical University

Key points

1. The development of metanephros 2. Two sets of genital tract at indifferent stage Anhui Medical University Assignments • Describe the development of metanephros? • What are the two sets of genital tract at indifferent stage? Describe their development at a later stage.