The Genital Organs Differentiation

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    The Genital Organs

    DifferentiationBy: E. Suryadi

    Faculty of Medicine GMU

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    Introduction

    At fertilization the genetic sex of an embryo isdetermined, there is no morphological indicationof sex until the 7th week, when the gonads beginacquire sexual characteristics.

    This period of early genital development isreferred to as indifferent stage organs.

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

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    Differentiation of early embryonic

    tissuesBlastomere

    Endoderm Mesoderm

    Ectoderm

    ParaxialisIntermediate

    Lateralis

    Splachnicus SomaticusCrista urogenitalis

    Crista gonadalisMesothelium

    mesenchym

    Embryoblast

    Trophoblast Allantois

    Primordial

    GerminalCells

    Migration

    Spermatogonium

    Sertoli Cell

    Leydig CellTDFIndifferent

    Gonad

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    Embryonic structure

    ??-Male genital organs

    -Female genital organs

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    Ovarium

    Tuba uteri

    Uterus

    Vagina Clitoris

    Labium minor

    Labium major

    Testis Epididymis

    Ductus deferens

    Seminal gland

    Prostate gland

    urethra

    penis

    scrotum

    Embryonic structure

    (Indifferent gonad) Mesonephric tubulus

    Mesonephric duct

    Paramesonephricduct

    Urogenital sinus

    Phallus

    Urogenital folds

    Labioscrotal swelling

    Femalegenital

    organ

    Male

    genitalorgan

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    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

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    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 urogenitalridge 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

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    Origin of The Germ Cell

    Primordial germ cell (PGC) during third weekcan be found on the posterior wall of the Yolksac 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 theposterior 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

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    The Multiplication of The

    Germ Cell by Mitosis The number of primary germ cell (PGC)

    increases during their migration from a fewhundred 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 andspermatogonia is different

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    Sex Determination Genetic sex is established at fertilization

    Gonadal sex is determined by the sexchromosome ( X or Y )

    At the short arm Y chromosome has SRY genefor TDF as a strong testis determining effect onthe medulla of indifferent gonad.

    TDF induces the gonadal cords to condense andextend into medulla of indifferent gonad, wheresex cord branch and anastomose to form therete testis and gonadal cord become seminiferuscord.

    The gonads then determine the type of sexualdifferentiation that occurs in the genital ductsand external genitalia.

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    Development of testes

    In embryos with a Y chromosome theprimary sex cords condense and extendinto medulla of gonad.

    Here they branch and their endsanastomose to form the rete testis.

    The prominent sex cords, calledseminiferus cord

    Soon lose their connections with thegerminal epithelium because of thedevelopment of a thick fibrous capsule

    called tunica albuginea

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    Chromosome Y

    In Chromosome Y laid the SRY gene ( for a testisdetermining factor (TDF)), which is located in the shortarm region of the Y chromosome.

    At sixth week SRY protein is produced so that :

    1. sertoli precursor (mesothelium cells) aggregate intocords become tubulus seminiferus sertoli cellproduce Mullerian inhibitory factor(MIF) and

    2. mesenchymal cells of the gonadal ridge begin todifferentiate into Leydig cell Leydig cells producetestosteron

    Mullerian inhibitory factor and testosteron influence thedevelopment of the genital duct and the genital externalto differentiate in the male direction.

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    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.

    Penis

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    Indifferent

    gonadTestis

    Y chromosome

    Testis

    Determining

    factor Leydig cells

    Sertoli cells

    Testosterone

    Androgen

    Binding

    Factor

    Mullerian

    Inhibiting Factor

    Mullerian

    Duct Degenerates

    Germ cells Spermatozoa

    Wolffian

    Duct

    Epididymis

    Vas deferens

    Seminal vesicle

    5-alfa

    reductase

    Dihydro-testosterone

    Urethral endothelium Prostate

    Genital swelling Scrotum

    Tuberculum genitale Penis

    The developing process of the male genital organs

    SOX9

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    Development of Gonads

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    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 todevelop to the tuba uterina, and uterus.

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    Development of Genital Duct

    Testis fetal menghasilkan hormon untuk maskulinisasi yitestosteron, 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.

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    Development of Male Genital Ducts

    and Glands

    1. Prostate

    The glandular epithelium of

    the prostate

    differentiates from theendodermal cells, and

    the associated

    mesenchyme

    differentiates into thedense stroma and

    smooth muscle of the

    prostate.

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    Development of Male External Genitalia

    Inducedby testosterone which produced by the

    interstitial cells of the fetal testes.

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    Cont male external genital

    The phallusdevelop 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 itsbreakdown it forms the prepuce (foreskin), which

    covering fold of skin.

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    Development of Inguinal Canals

    The inguinal canals form pathways for the testes todescend from theirintra-abdominal position through the

    anterior abdominal wall into the scrotum

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    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 resultingfrom the growth of abdominal viscera

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    Cont.

    By 26 weeks, the testes have descendedretroperitoneally (external to the peritoneum)

    from the posterior abdominal wall to the deep

    inguinal rings

    .This change in position occurs as the fetalpelvis enlarges and the trunk of the embryo

    elongates.

    Little is known about the cause of testicular

    descent through the inguinal canals into thescrotum, but the process is controlled by

    androgens (e.g., testosterone) produced by the

    fetal testes.

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    Male derivative Indifferent structure Female derivative

    testis gonad ovary

    Spermatozoa Primordial germ cells Ova

    Seminiferus tubulus(sertoli cells)

    Sex cords Follicular cells

    Efferent ductules Mesonephric tubules Epoophoron

    Epididymal duct,

    ductus defferens

    Mesonephric (Wolffian)

    duct

    Degenerates (ovarian,

    round ligament )

    Degenerates Paramesonephric

    (Mullerian) duct

    Uterine tubes, uterus,

    part of vagina

    Bladder, protaste

    urethra

    Early urogenital sinus Bladder, paraurethral

    gland, urethra, vagina

    Lower urethra, bulbo

    urethral gland

    Definitive urogenital sinus Vestibule, Major

    vestibular gland

    Penis Genital tubercle = phallus clitoris

    Floor of penile urethra Urogenital fold Labia minora