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

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<big><center>[[Reproductive System|'''BACK TO REPRODUCTIVE SYSTEM''']]</center></big>
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<big><center>[[Reproductive_System#Fertilisation.2C_Implantation_and_Early_Embryonic_Development|'''BACK TO FERTILISATION , IMPLANTATION and EARLY EMBRYONIC DEVELOPMENT''']]</center></big>
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[[Image:Overview of Sexual Differentiation.jpg|thumb|right|150px|Overview of Sexual Differentiation,Copyright RVC 2008]]
 
  
 
= Genetic Sex =
 
= Genetic Sex =
 
* Established at the time of '''fertilisation'''.
 
* Established at the time of '''fertilisation'''.
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* The foetus receives its genetic endowment in two equal portions from the male gamete ('''spermatozoon''') and female gamete ('''oocyte''').
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* 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.
 
* 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.
 
* '''Females''' have '''XX''' chromosomes.  All oocytes contain one X chromosome, they are the '''homogametic''' sex.
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* The '''Y''' chromosome is required to '''initiate male development'''.
 
* The '''Y''' chromosome is required to '''initiate male development'''.
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* In absence of the Y chromosome, female gonads (ovaries) will develop.
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* 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).  
 
* 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 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)
 
* SRY encodes the protein '''Testes Determining Factor''' (TDF)
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* The presence of SRY alone is sufficient to ensure development of male gonads (testes).
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* The presence of SRY alone is sufficient to ensure development of male gonads (Testes).
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* Female is the default sex, in absence of SRY female gonads (ovaries) will develop.
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* 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'''.
 
* Subsequent gonadal development is dependent on a normal population of '''germ cells'''.
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* Normal oocyte growth requires the activity of both X chromosomes.
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* Normal Oocyte growth requires the activity of both X chromosomes.
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* Normal spermatogenesis requires the activity of no more than one X chromosome.
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* Normal Spermatogenesis requires the activity of no more than one X chromosome.
  
  
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* 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 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).
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* Sex cords with a basement membrane become '''semniferous cords''' which give rise to '''semniferous tubules'''.
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* Sex cords with a basement membrane become '''Semniferous Cords''' which give rise to '''Semniferous Tubules'''.
 
* '''Within the semniferous cords''' are two cell populations:
 
* '''Within the semniferous cords''' are two cell populations:
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** '''Primordial germ cells'''  - Prospermatogonia which give rise to '''spermatozoa'''
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** '''Primordial germ cells'''  - Prospermatogonia which give rise to '''Spermatozoa'''
 
** '''Mesodermal cord cells''' which give rise to '''Sertoli cells'''
 
** '''Mesodermal cord cells''' which give rise to '''Sertoli cells'''
 
* '''Between cords''', the loose mesenchyme undergoes '''vascularisation''' and develops as '''stromal tissue'''.
 
* '''Between cords''', the loose mesenchyme undergoes '''vascularisation''' and develops as '''stromal tissue'''.
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* Within the stromal tissue, cells condense into clusters to form specialized endocrine units - the interstitial '''Leydig's  cells'''
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* Within the stromal tissue, cells condense into clusters to form specialized endocrine units - the interstitial '''Leydig Cells'''
 +
 
  
 
== Female ==
 
== 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.
 
* 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.
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* Small clusters of mesenchyme surround the germ cells to initiate formation of '''primary follicles''', characteristic of the ovary.
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* Small clusters of mesenchyme surround the germ cells to initiate formation of '''Primary Follicles''', characteristic of the Ovary.
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* In follicles
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* In follicles:
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** '''Mesenchymal cells''' give rise to '''granulosa cells'''
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** '''Mesenchymal cells''' give rise to '''Granulosa cells'''
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** '''Germ cells''' give rise to '''oocytes'''
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** '''Germ cells''' give rise to '''Oocytes'''
  
  
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== Foetal sex differentiation ==
 
== Foetal sex differentiation ==
  
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* Endocrine activity of the ovaries is NOT essential for sex differentiation during foetal life, abnormal ovarian development will have no effect until puberty.
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* 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:  
 
* Testes secrete two essential hormones:  
−
** '''Steroidal hormones''' (mainly C19 androgens) from '''leydig's cells'''
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** '''Steroidal hormones''' (mainly C19 androgens) from '''Leydig cells'''
−
** '''Mullarian Inhibiting Hormone''' (MIH) also known as '''Anti-Mullarian Hormone''' (AMH) from '''Sertoli cells'''
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** '''Mullarian Inhibiting Hormone''' (MIH) also known as '''Anti-Mullarian Hormone''' (AMH) from '''Sertoli Cells'''
 
* In absence of these testicular hormones, female differentiation occurs.
 
* 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.
 
* Thus, sexual differentiation must be actively diverted down the male route, the female route requires no active intervention.
  
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----
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 +
= Internal Genetalia =
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* Male: '''Wolffian Duct''' developes from the '''Mesonephric Duct'''
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* Female: '''Mullarian Ducts''' develop from the '''Paramesonephric Duct'''
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* 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.
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----
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= External Genetalia =
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 +
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== 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'''
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** '''Genital Tubercle''' expands to give rise to the '''Glans Penis'''
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== Female ==
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* Development is ensured by the absence of Testosterone, it is independent of Ovarian endocrine activity.
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* '''Urethral folds''' and '''Genital Swellings''' remain separate to form the '''Labia Minora and Majora'''.
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* '''Genital tubercle''' forms the '''Clitoris'''
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* Exposure of the female tract to Androgens will masculinise external genetalia.
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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.
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 +
----
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= Sexual Differentiation of the Brain =
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== Male ==
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* '''Testosterone''' secreted into the blood reaches the brain.
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* Converted to Dehydrotestosterone and '''Oestradiol''' by Aromatase enzymes in the Hypothalamus.
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* Oestradiol masculinises the brain
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 +
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== Female ==
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* '''Alpha Fetoprotein''' binds Oestradiol, preventing it from crossing the blood-brain barrier.
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* Oestradiol cannot access the Hypothalamus
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* Protects female brain from masculising effects of Oestradiol.
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----
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== Associated Disorders ==
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* [[Fertilisation, Implantation and Early Embryonic Development -Turner's Syndrome - Anatomy & Physiology|Turner's Syndrome]]
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* [[Fertilisation, Implantation and Early Embryonic Development -Kleinfelter's Syndrome - Anatomy & Physiology|Kleinfelter's Syndrome]]
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* [[Fertilisation, Implantation and Early Embryonic Development -Testicular Feminisation - Anatomy & Physiology|Testicular Feminisation]]
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* [[Fertilisation, Implantation and Early Embryonic Development -Adrenogenital Syndrome - Anatomy & Physiology|Adrenogenital Syndrome]]
  
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* [[Fertilisation, Implantation and Early Embryonic Development -Intersex - Anatomy & Physiology|Intersex]]
  
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[[Category:Pregnancy and Parturition]]
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* [[Fertilisation, Implantation and Early Embryonic Development -Bovine Freemartinism - Anatomy & Physiology|Bovine Freemartinism]]
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[[Category:Bullet Points]]
 

Revision as of 12:24, 21 July 2008

BACK TO REPRODUCTIVE SYSTEM
BACK TO FERTILISATION , IMPLANTATION and EARLY EMBRYONIC DEVELOPMENT



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

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