Difference between revisions of "Sexual Differentiation - Anatomy & Physiology"

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* At this stage it is not possible to discriminate between male and female gonads.
 
* At this stage it is not possible to discriminate between male and female gonads.
 
* Y chromosomal determination of gonadal sex is only visible when primordial germ cell colonisation is complete.
 
* Y chromosomal determination of gonadal sex is only visible when primordial germ cell colonisation is complete.
 
 
[[Image:Sexual Differentiation primordial germ cell migration a.jpg|right|thumb|250px|<small><center> Schematic showing Early Sexual Differentiation. (Courtesy of Pathways to Pregnancy and Parturition, Senger)</center></small>]]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
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* '''Between cords''', the loose mesenchyme undergoes '''vascularisation''' and develops as '''stromal tissue'''.
 
* '''Between cords''', the loose mesenchyme undergoes '''vascularisation''' and develops as '''stromal tissue'''.
 
* Within the stromal tissue, cells condense into clusters to form specialized endocrine units - the interstitial '''Leydig Cells'''
 
* Within the stromal tissue, cells condense into clusters to form specialized endocrine units - the interstitial '''Leydig Cells'''
 
 
[[Image:Sexual Differentiation early male a.jpg|right|thumb|250px|<small><center> Schematic showing Early Sexual Differentiation in the Male. (Courtesy of Pathways to Pregnancy and Parturition, Senger)</center></small>]]
 
 
[[Image:Sexual Differentiation early male b.jpg|right|thumb|250px|<small><center> Schematic showing Early Sexual Differentiation in the Male. (Courtesy of Pathways to Pregnancy and Parturition, Senger)</center></small>]]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
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** '''Mesenchymal cells''' give rise to '''Granulosa cells'''
 
** '''Mesenchymal cells''' give rise to '''Granulosa cells'''
 
** '''Germ cells''' give rise to '''Oocytes'''
 
** '''Germ cells''' give rise to '''Oocytes'''
 
 
 
 
[[Image:Sexual Differentiation early female.jpg|right|thumb|250px|<small><center> Schematic showing Early Sexual Differentiation in the Female. (Courtesy of Pathways to Pregnancy and Parturition, Senger)</center></small>]]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
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** Cranial Vagina
 
** Cranial Vagina
 
* Normal Ovarian activity is NOT essential for the development of normal female internal genetalia.
 
* Normal Ovarian activity is NOT essential for the development of normal female internal genetalia.
 
 
[[Image:Sexual Differentiation internal genitalia.jpg|right|thumb|250px|<small><center> Schematic showing Development of Internal Genitalia. Copyright RVC 2008 (Courtesy of Proff.R.Abayesekara (RVC))</center></small>]]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
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* Failure of proper endocrine communication between the gonads, internal and external genitalia can lead to '''dissociation''' of gonadal and genital sex.
 
* Failure of proper endocrine communication between the gonads, internal and external genitalia can lead to '''dissociation''' of gonadal and genital sex.
  
 
+
----
 
 
[[Image:Sexual Differentiation external genitalia.jpg|right|thumb|250px|<small><center> Schematic showing Development of External Genitalia. Copyright RVC 2008 (Courtesy of Proff.R.Abayesekara (RVC))</center></small>]]
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
== Sexual Differentiation of the Brain ==
 
== Sexual Differentiation of the Brain ==

Revision as of 08:38, 8 July 2008

Genetic Sex

  • Established at the time of fertilisation.
  • The foetus receives its genetic endowment in two equal portions from the male gamete (Spermatozoon) and female gamete (Oocyte).
  • The X sex chromosome is larger than the Y sex chromosome.
  • Females have XX chromosomes. All oocytes contain one X chromosome, they are the homogametic sex.
  • Males have XY chromosomes. Spermatozoa form two distinct populations, one containing X chromosomes and one containing Y chromosomes. They are the heterogametic sex.


  • The Y chromosome is required to initiate male development.
  • In absence of the Y chromosome, female gonads (Ovaries) will develop.
  • The prime male determining gene is SRY (sex determining region of the Y chromosome).
  • SRY is a very small piece of DNA that acts as a molecular switch to regulate structural genes and autosomal chromosomes, determining if and when they are to be activated.
  • SRY encodes the protein Testes Determining Factor (TDF)
  • The presence of SRY alone is sufficient to ensure development of male gonads (Testes).
  • Female is the default sex, in absence of SRY female gonads (Ovaries) will develop.


  • Subsequent gonadal development is dependent on a normal population of germ cells.
  • Normal Oocyte growth requires the activity of both X chromosomes.
  • Normal Spermatogenesis requires the activity of no more than one X chromosome.


  • Early development of gonads proceeds similarly in both sexes. The gonads are derived from two distinct tissues:
    • Somatic mesenchymal tissue forms the matrix of the gonad
    • Primordial germ cells form the gametes


  • Genital ridge forms from somatic mesenchyme.
  • Primordial germ cells migrate to the genital ridge.
  • At this stage it is not possible to discriminate between male and female gonads.
  • Y chromosomal determination of gonadal sex is only visible when primordial germ cell colonisation is complete.


MALE

  • Sex cord cells proliferate to form the testes cord. During this period SRY is expressed for the first time within Sertoli cells (SRY is NOT expressed in primordial germ cells).
  • Sex cords with a basement membrane become Semniferous Cords which give rise to Semniferous Tubules.
  • Within the semniferous cords are two cell populations:
    • Primordial germ cells - Prospermatogonia which give rise to Spermatozoa
    • Mesodermal cord cells which give rise to Sertoli cells
  • Between cords, the loose mesenchyme undergoes vascularisation and develops as stromal tissue.
  • Within the stromal tissue, cells condense into clusters to form specialized endocrine units - the interstitial Leydig Cells


FEMALE

  • At the time the male gonad is undergoing marked changes under the direction of SRY, the female gonad continues to appear indifferent and does not express SRY.
  • Small clusters of mesenchyme surround the germ cells to initiate formation of Primary Follicles, characteristic of the Ovary.
  • In follicles:
    • Mesenchymal cells give rise to Granulosa cells
    • Germ cells give rise to Oocytes


Foetal sex differentiation

  • Endocrine activity of the Ovaries is NOT essential for sex differentiation during foetal life, abnormal ovarian development will have no effect until puberty.
  • Testes secrete two essential hormones:
    • Steroidal hormones (mainly C19 androgens) from Leydig cells
    • Mullarian Inhibiting Hormone (MIH) also known as Anti-Mullarian Hormone (AMH) from Sertoli Cells
  • In absence of these testicular hormones, female differentiation occurs.
  • Thus, sexual differentiation must be actively diverted down the male route, the female route requires no active intervention.



Internal Genetalia

  • Male: Wolffian Duct developes from the Mesonephric Duct
  • Female: Mullarian Ducts develop from the Paramesonephric Duct
  • This is dependent on appropriate hormonal influence.


MALE

  • MIH from Sertoli cells and Androgens from Leydig cells prevent spontaneous development of female internal genetalia.
  • Androgens actively maintain Wolffian Ducts, which give rise to male internal genetalia:
    • Epididymis
    • Vas Deferens
    • Vesicular Glands/ Seminal Vesicles
  • MIH causes Mullarian Ducts to regress


FEMALE

  • Wolffian Ducts spontaneously regress in absence of Androgens.
  • Mullarian Ducts persist to give rise to female internal genetalia:
    • Oviducts
    • Uterus
    • Cervix
    • Cranial Vagina
  • Normal Ovarian activity is NOT essential for the development of normal female internal genetalia.

External Genetalia

MALE

  • Potential to develop male of female external genetalia. Testosterone is required to develop male external genetalia.
  • Androgen secretion from the Testes induces:
    • Urethral folds to fuse to allow enclosure of the urethral tube. This, together with the cells from the genital swelling, forms the shaft of the Penis.
    • Genital swellings fuse in the midline to allow formation of the Scrotum
    • Genital Tubercle expands to give rise to the Glans Penis


FEMALE

  • Development is ensured by the absence of Testosterone, it is independent of Ovarian endocrine activity.
  • Urethral folds and Genital Swellings remain separate to form the Labia Minora and Majora.
  • Genital tubercle forms the Clitoris


  • Exposure of the female tract to Androgens will masculinise external genetalia.
  • Failure of proper endocrine communication between the gonads, internal and external genitalia can lead to dissociation of gonadal and genital sex.

Sexual Differentiation of the Brain

MALE

  • Testosterone secreted into the blood reaches the brain.
  • Converted to Dehydrotestosterone and Oestradiol by Aromatase enzymes in the Hypothalamus.
  • Oestradiol masculinises the brain


FEMALE

  • Alpha Fetoprotein binds Oestradiol, preventing it from crossing the blood-brain barrier.
  • Oestradiol cannot access the Hypothalamus
  • Protects female brain from masculising effects of Oestradiol.

Associated Disorders

Turner's Syndrome
Kleinfelter's Syndrome
Testicular Feminisation
Adrenogenital Syndrome
Intersex
Bovine Freemartinism