Difference between revisions of "Sexual Differentiation - Anatomy & Physiology"
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+ | <big><center>[[Reproductive System|'''BACK TO REPRODUCTIVE SYSTEM''']]</center></big> | ||
+ | |||
+ | <big><center>[[Reproductive_System#Fertilisation.2C_Implantation_and_Early_Embryonic_Development|'''BACK TO FERTILISATION , IMPLANTATION and EARLY EMBRYONIC DEVELOPMENT''']]</center></big> | ||
+ | |||
+ | |||
− | |||
= Genetic Sex = | = Genetic Sex = | ||
* Established at the time of '''fertilisation'''. | * Established at the time of '''fertilisation'''. | ||
− | * The foetus receives its genetic endowment in two equal portions from the male gamete (''' | + | * 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. | ||
Line 11: | Line 15: | ||
* The '''Y''' chromosome is required to '''initiate male development'''. | * The '''Y''' chromosome is required to '''initiate male development'''. | ||
− | * In absence of the Y chromosome, female gonads ( | + | * 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) | ||
− | * The presence of SRY alone is sufficient to ensure development of male gonads ( | + | * 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 ( | + | * 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'''. | ||
− | * Normal | + | * Normal Oocyte growth requires the activity of both X chromosomes. |
− | * Normal | + | * Normal Spermatogenesis requires the activity of no more than one X chromosome. |
Line 39: | Line 43: | ||
* 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). | ||
− | * Sex cords with a basement membrane become ''' | + | * 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: | ||
− | ** '''Primordial germ cells''' - Prospermatogonia which give rise to ''' | + | ** '''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'''. | ||
− | * Within the stromal tissue, cells condense into clusters to form specialized endocrine units - the interstitial '''Leydig | + | * 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. | ||
− | * Small clusters of mesenchyme surround the germ cells to initiate formation of ''' | + | * Small clusters of mesenchyme surround the germ cells to initiate formation of '''Primary Follicles''', characteristic of the Ovary. |
− | * In follicles | + | * In follicles: |
− | ** '''Mesenchymal cells''' give rise to ''' | + | ** '''Mesenchymal cells''' give rise to '''Granulosa cells''' |
− | ** '''Germ cells''' give rise to ''' | + | ** '''Germ cells''' give rise to '''Oocytes''' |
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== Foetal sex differentiation == | == Foetal sex differentiation == | ||
− | * Endocrine activity of the | + | * 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 ''' | + | ** '''Steroidal hormones''' (mainly C19 androgens) from '''Leydig cells''' |
− | ** '''Mullarian Inhibiting Hormone''' (MIH) also known as '''Anti-Mullarian Hormone''' (AMH) from '''Sertoli | + | ** '''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. | ||
+ | ---- | ||
+ | |||
+ | = 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 == | ||
+ | |||
+ | |||
+ | |||
+ | |||
+ | * [[Fertilisation, Implantation and Early Embryonic Development -Turner's Syndrome - Anatomy & Physiology|Turner's Syndrome]] | ||
+ | |||
+ | * [[Fertilisation, Implantation and Early Embryonic Development -Kleinfelter's Syndrome - Anatomy & Physiology|Kleinfelter's Syndrome]] | ||
+ | |||
+ | * [[Fertilisation, Implantation and Early Embryonic Development -Testicular Feminisation - Anatomy & Physiology|Testicular Feminisation]] | ||
+ | |||
+ | * [[Fertilisation, Implantation and Early Embryonic Development -Adrenogenital Syndrome - Anatomy & Physiology|Adrenogenital Syndrome]] | ||
+ | * [[Fertilisation, Implantation and Early Embryonic Development -Intersex - Anatomy & Physiology|Intersex]] | ||
− | [[ | + | * [[Fertilisation, Implantation and Early Embryonic Development -Bovine Freemartinism - Anatomy & Physiology|Bovine Freemartinism]] |
− |
Revision as of 12:23, 21 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.