The Genital Organs Differentiation

By: E. Suryadi Faculty of Medicine GMU

Introduction

At fertilization the genetic sex of an embryo is determined, there is no morphological indication of sex until the 7th week, when the gonads begin acquire sexual characteristics. This period of early genital development is referred to as indifferent stage organs.

How the genital organs differentiation process? And what are the influence factors?

Differentiation of early embryonic tissue s Blastomere

Embryoblast Trophoblast Endoderm Mesoderm Allantois Ectoderm Primordial Germinal Cells

Paraxialis Intermediate

Lateralis

Migration

Crista urogenitalis

Splachnicus

Somaticus
Spermatogonium Sertoli Cell Leydig Cell

Indifferent Gonad

Crista gonadalis Mesothelium mesenchym

TDF

Embryonic structure ?? -Male genital organs -Female genital organs

Embryonic structure
(Indifferent gonad) Mesonephric tubulus Mesonephric duct Paramesonephric duct Urogenital sinus Phallus Urogenital folds Labioscrotal swelling

Ovarium Tuba uteri Uterus Vagina Clitoris Labium minor Labium major

Female genital organ

Testis Epididymis Ductus deferens Seminal gland Prostate gland urethra penis scrotum

Male genital organ

Development of The Gonads

The gonad Cells are derived from three sources of cells: 1. mesothelium lining of the abdominal wall and 2. underlying mesenchyme 3. primordial germ cells

The Indifferent Gonads

Gonadal development is the first indicated during the fifth week when a thickened area of coelomic epithelium. It develops on the medial aspect of urogenital ridge and then becomes gonadal ridge Soon finger-like epithelium cords is formed, called primary sex cords, grow into the underlying mesenchyme. The indifferent gonad now consists of an outer as a cortex and an inner as a medulla

Origin of The Germ Cell

Primordial germ cell (PGC) during third week can be found on the posterior wall of the Yolk sac near the origin of the allantois They are large size and clear cytoplasm PGC reach the gonads by migration (amoeboid movement) around the wall of the posterior gut and then through the dorsal mesentery to the gonadal ridge. During migration is guided by laminin and fibronectin (Extra- Cellular Matrix) A chemotactic influence from the gonads guides the final stage of the migration

The Multiplication of The Germ Cell by Mitosis

The number of primary germ cell (PGC) increases during their migration from a few hundred to a few thousand - after they have settled down in the gonad, from a few thousand to about 7 million Mitotically active germ cell: - in female are called oogonia - in male are called spermatogonia The pattern of mitotic activity of oogonia and spermatogonia is different

Sex Determination

Genetic sex is established at fertilization Gonadal sex is determined by the sex chromosome ( X or Y ) At the short arm Y chromosome has SRY gene for TDF as a strong testis determining effect on the medulla of indifferent gonad. TDF induces the gonadal cords to condense and extend into medulla of indifferent gonad, where sex cord branch and anastomose to form the rete testis and gonadal cord become seminiferus cord. The gonads then determine the type of sexual differentiation that occurs in the genital ducts and external genitalia.

Development of testes
In embryos with a Y chromosome the primary sex cords condense and extend into medulla of gonad. Here they branch and their ends anastomose to form the rete testis. The prominent sex cords, called seminiferus cord Soon lose their connections with the germinal epithelium because of the development of a thick fibrous capsule called tunica albuginea

The seminiferus cords develop into the seminiferus tubules, the tubuli recti and the rete testis. The seminiferus tubules are separated by mesenchyme which give rise to the interstitial cells (Leydig cell) The walls of the seminiferus tubules are composed of two kinds of cells: sustentacular cells of Sertoli derived from germinal epithelium (mesothelium) and spermatogonia derived from the primordial germ cells.

Chromosome Y

In Chromosome Y laid the SRY gene ( for a testis determining factor (TDF)), which is located in the short arm region of the Y chromosome. At sixth week SRY protein is produced so that : 1. sertoli precursor (mesothelium cells) aggregate into cords become tubulus seminiferus sertoli cell produce Mullerian inhibitory factor (MIF) and 2. mesenchymal cells of the gonadal ridge begin to differentiate into Leydig cell Leydig cells produce testosteron Mullerian inhibitory factor and testosteron influence the development of the genital duct and the genital external to differentiate in the male direction.

Molecular regulation of genital duct development

SRY ---> master gene for testes development. SRY also upregulates SF1 ---> acts through another transcription factor (SOX9) to induce defferentiation of sertoli and leydig cells. Sertoli cells produce MIS/AMH that cause regression which enters cells of target tissues where it may remain or be converted to dihydrotestoterone by a 5 reductase enzyme. Testosteron + dihydrotestoterone bind to a spesific high-affinity intraceluller receptor protein, and ultimately binds to DNA to regulate trancription of tissue-spesific genes and their protein product.

Tuberculum genitale Genital swelling

Penis Scrotum

Urethral endothelium
Y chromosome

Prostate
Dihydro-testosterone 5-alfa reductase Testosterone Androgen Binding Factor Germ cells

Indifferent gonad

Testis Determining Leydig cells factor Testis SOX9 Sertoli cells

Wolffian Duct

Mullerian Inhibiting Factor

Epididymis Vas deferens Seminal vesicle Spermatozoa

Mullerian Duct

Degenerates

The developing process of the male genital organs

Development of Gonads

Development of The Genital Ducts

The Indifferent Stage consist two pairs of genital ducts: 1.ductus mesonephridicus (Wolffian ducts)

2.ductus paramesonephridicus (Mullerian ducts)

Development of Genital Ducts

Mesonephric duct epididymis , defferen duct & ejaculatory duct, seminal gland The Paramesonephric duct develop lateral to the gonads and mesonephric ducts, pass caudally, parallel to the mesonephric ducts, until they reach the future pelvic region of the embryo, and to develop to the tuba uterina, and uterus.

Development of Genital Duct

Testis fetal menghasilkan hormon untuk maskulinisasi yi testosteron, dan substansi inhibiting mullerian (MIS). Sel sertoli mulai menghasilkan MIS pd minggu ke-6 s/d -7. Sel leydig mulai menghasilkan testosteron mulai minggu ke-8.

Development of Male Genital Ducts and Glands

Prostate The glandular epithelium of the prostate differentiates from the endodermal cells, and the associated mesenchyme differentiates into the dense stroma and smooth muscle of the prostate.
1.

Bulbourethral Glands

Develop from paired outgrowths from the spongy part of the urethra. The smooth muscle fibers and the stroma differentiate from the adjacent mesenchyme.

Development of Male External Genitalia

Induced by testosterone which produced by the interstitial cells of the fetal testes.

Cont male external genital

The phallus develop penis The urogenital folds forms the lateral wall of the urethral groove lined by a proliferation of endodermal cells, the urethral plate, The urogenital folds fuse each other and forms spongy urethra The surface ectoderm forms the penile raphe and enclosing the spongy urethra within the penis During the 12th week a circular ingrowth of ectoderm occurs at the periphery of the glans penis, and when its breakdown it forms the prepuce (foreskin), which covering fold of skin.

Development of Inguinal Canals

The inguinal canals form pathways for the testes to descend from their intra-abdominal position through the anterior abdominal wall into the scrotum

Descent of the Testes

This is association with - Enlargement of testes and - atrophy of mesonepros, - atrophy of paramesonepridicus duct, - enlargement of processus vaginalis, - enlargement of pelvis foetal, - increase in abdominal pressure resulting from the growth of abdominal viscera

Cont.
By 26 weeks, the testes have descended retroperitoneally (external to the peritoneum) from the posterior abdominal wall to the deep inguinal rings .This change in position occurs as the fetal pelvis enlarges and the trunk of the embryo elongates. Little is known about the cause of testicular descent through the inguinal canals into the scrotum, but the process is controlled by androgens (e.g., testosterone) produced by the fetal testes.

Male derivative
testis Spermatozoa

Indifferent structure gonad Primordial germ cells

Female derivative ovary Ova

Seminiferus tubulus (sertoli cells)

Efferent ductules Epididymal duct, ductus defferens Degenerates Bladder, protaste urethra Lower urethra, bulbo urethral gland Penis Floor of penile urethra

Sex cords
Mesonephric tubules Mesonephric (Wolffian) duct Paramesonephric (Mullerian) duct Early urogenital sinus Definitive urogenital sinus Genital tubercle = phallus Urogenital fold

Follicular cells
Epoophoron Degenerates (ovarian, round ligament ) Uterine tubes, uterus, part of vagina Bladder, paraurethral gland, urethra, vagina Vestibule, Major vestibular gland clitoris Labia minora