63 Development of the reproductive system Flashcards
What does sexual reproduction create?
- Creates genetic variety - useful for adapting to constantly changing and challenging environments
- Some gene variants may become advantageous in future under some environmental constraint or insult
Sexual reproduction requires the formation of sperm and oocytes that are ___ ?
Haploid
What does fertilisation re-establish?
Re-establishes the diploid state and chromosomal sex is determined
Definition of sexual differentiation?
Process by which male and females become structurally and functionally dissimilar
Definition of sex determination?
Initiation of the male differentiation pathway by SRY
What happens if the developing testes (or ovaries) are removed before sexual differentiation?
Female differentiation ensues
What does the development of sexually differentiated gonads drive?
Further sexual differentiation of the reproductive tracts
What are specialised structures of the female reproductive tract needed for?
To nurture the growing embryo and infant after birth
How many chromosomes in human somatic cells? (female vs male)
- 22 pairs of autosomes
- 1 pair fo sex chromosomes (XX or XY)
- Female (46, XX) - homogametic
- Male (46, XY) - heterogametic
What occurs to the number of chromosomes during meiosis? (female vs male)
Germ cells produce gametes with half the number of chromosomes (haploid)
- Oocytes (23, X)
- Spermatozoa (23, X or 23, Y)
What chromosomes do not normally influence gonad differentiation?
Autosomes or “X” chromosomes
The genetic determinant of sex is the presence or absence of the _____ ? Leads to?
Y chromosome
- Presence of Y chrom –> male gonads (testes)
- Absence of Y chrom –> female gonads (ovaries)
What happens once gonadal differentiation is initiated?
The developing gonad directs further development events that produce sexual dimorphism
or
Gonadal hormones trigger the cascades that produce sexual dimorphic development of the reproductive tract
Features of Y chromosome
- Small and most of its DNA is condensed
- Encodes only ~ 48 genes - involved in skeletal growth, tooth development, with few genes involved with testes development
- Regulatory gene - controls other developmental genes and so indirectly controls the formation of testes
Where are many of the genes required for testes development located?
- Autosomes
- X chromosome
• Y chromosome has regulatory gene that control these other developmental genes and so indirectly controls the formation of testes
How does non-disjunction occur between the X and Y chromosome?
Y chromosome retains regions of homology with the X chromosome that permits pairing during meiosis but error can occur (non-disjunction)
What is the non-disjunction in XY females?
Part of the short arm of the Y chromosome is missing or mutated in XY females
What is the non-disjunction in XX males?
- A section of the Y chromosome translocated to an autosome or X chromosome
- This region contain the gene SRY (sex-determining region of the Y chromosome)
What is SRY?
• Sex-determining region of the Y chromosome
• Encodes a DNA binding protein (transcription factor)
that regulates expression of genes on other chromosomes responsible for testes differentiation
Testes and ovaries form from which two distinct cell types?
Gonadal differentiation
- Somatic mesenchyme
2. Primordial germ cells
What is the genital ridge formed by?
Gonadal differentiation
Proliferation of the surface epithelium and condensation of mesenchyme forming sex chords
Gonads are identical in both sexes until which week of development?
(Gonadal differentiation)
7th week
Where do primordial germ cells (PGCs) originate from?
Gonadal differentiation
Epiblast
Where and when are the primordial germ cells (PGCs) first identifiable?
(Gonadal differentiation)
- In the wall of the yolk sac
* ~ 2 weeks
How many primordial germ cells first appear and what do they undergo?
(Gonadal differentiation)
- ~ 10 PGCs appear
* Undergo mitotic divisions en route to the genital ridge (~ 2000 arrive)
Where do the primordial germ cells (PGCs) migrate into? Driven by?
(Gonadal differentiation)
- Migrate into genital ridge
* Driven by chemotaxis
What happens in week 6 with the primordial germ cells (PGCs)?
(Gonadal differentiation)
- Invade the genital ridges
* Become surrounded by the primitive medullary sex cords
What happens if the migration of primordial germ cells (PGCs) fails to enter the genital ridge?
(Gonadal differentiation)
Gonads do not develop
Primordial germ cells (PGCs) have an inductive influence on what?
(Gonadal differentiation)
PGCs have an inductive influence on development of the gonad into ovaries and testes but no role driving sexual dimorphism
How do the gonads form from weeks 0-6?
Gonadal differentiation
- Genital ridge is formed by proliferation of the surface epithelium and condensation of mesenchyme forming sex cords
- PCGs migrate into the genital ridge driven by chemotaxis. By 6 weeks the PCGs invade the genital ridges and become surrounded by the primitive medullary sex cords
- Are identical until this point for both males and females
What happens to the primitive sex cords in males under the influence of the SRY gene?
(Gonadal differentiation -male)
Primitive sex cords proliferate and penetrate the medulla forming testis cords
When testis cords become looped, whats does is it in contact with?
(Gonadal differentiation -male)
Ingrowing mesonephric tubule called Rete testos
What comes to reside within the developing testis cords?
Gonadal differentiation -male
Primordial germ cells
Mesodermal cells differentiate into what cells in the testis cords?
(Gonadal differentiation -male)
Sertoli cells
Mesenchyme tissue in interstitial spaces develop into what cells?
(Gonadal differentiation -male)
Leydig cells
• Start to secrete testosterone by 8th week
What does testosterone influence?
Gonadal differentiation -male
Development of the genital ducts and external genitalia
What happens by 20 weeks to the testis cords?
Gonadal differentiation -male
- Testis cords are horse-shaped
* Composed of germ cells and Serotli cells
Male gonadal differentiation?
- Under the influence of the SRY gene, primitive sex cords proliferate and penetrate the medulla forming testis cords
- Testis cords become looped. Contact with the ingrowing mesonephric tubule called Rete testis
- Primordial germ cells come to reside within the developing testis cord
- Mesodermal cells differentiate into Sertoli cells in the cords
- Mesenchyme tissue in interstitial spaces develop into Leydig cells and start to secrete testosterone by the 8th week
- Testosterone influences the development of the genital ducts and external genitalia
- By 20 weeks the testis cords are horseshoe-shaped, composed of germ cells and Sertoli cells
Female development (past 6th week) due to the absence of Y chromosome, leads to the degeneration of what?
(Gonadal differentiation -female)
Medullary cords/ primitive sex cords
Where do corticol cords form from?
Gonadal differentiation -female
From proliferating surface epithelium forming distinct cell clusters around germ cells by 12 weeks
Cells proliferate and surround each oogonium (germ cell) with what?
(Gonadal differentiation -female)
Epithelial layer of follicular cells - forming primordial follicles
Germ cells are absolutely required for the formation of what?
(Gonadal differentiation -female)
Ovarian follicles
Female gonadal differentiation?
- Female development (after 6th week) is influenced by the absence of Y chromosome - leads to degeneration of medullary cords/ primitive sex cords
- Cortical cords form from proliferating surface epithelium forming distinct cell clusters around the germ cells by 12 weeks
- Cells proliferate and surround each oogonium (germ cell) with epithelial layer of follicular cells – forming primordial follicles
- Germ cells are absolutely required for the formation of the ovarian follicles
What are the precursors to the male and female internal genitalia?
(Formation of Genital Ducts)
At 7-8 weeks, embryos acquire dual ductal systems
What ducts give rise to the male genital ductal system?
Formation of Genital Ducts
Wolffian (mesonephric) ducts
What ducts give rise to the female genital ductal system?
Formation of Genital Ducts
Müllerian (paramesonephric) ducts
The developmental path of genital ducts depends on what?
Formation of Genital Ducts
Hormones secreted by the developing testis NOT the ovary
How are genital ducts formed?
- At 7-8 weeks embryo’s acquire dual ductal systems that are precursors to the male and female internal genitalia
- Wolffian (mesonephric) ducts give rise to the male genital ductal system
- Müllerian (paramesonephric) ducts give rise to the female genital ductal system
- The developmental path taken depends on hormones secreted by the developing testes not the ovary.
In males, what does SRY act in conjunction with?
Development of Internal Genitalia - Male
Other transcription factors such as SOX9 and SF-1 to stimulate the differentiation of Sertoli and Leydig cells
What do Sertoli cells express?
Development of Internal Genitalia - Male
Anti-Müllerian hormone (AMH)
What does anti-Müllerian hormone (AMH) lead to?
Development of Internal Genitalia - Male
Regression of the Müllerian/ paramesonephric ducts and prevents development of female structures
What do Leydig cells secrete?
Development of Internal Genitalia - Male
Testosterone which supports the development of the mesonephric ducts and leads to virilisation
How is the internal genitals of the male system developed?
In males, SRY acts in conjunction with other transcription factors: SOX9 and SF-1 (steroidogenic factor 1). These stimulate the differentiation of Sertoli and Leydig cells
- SERTOLI CELLS then express anti-mullerian hormone (AMH) which leads to regression of the Mullerian ducts and prevents development of female structures
- LEYDIG CELLS start secreting testosterone which supports the development of the Wolffian ducts and leads to virilisation.
Summary: Medullary cords develop and no cortical cords develop
What happens to the mesonephric and paramesonephric ducts in the absence of any hormones?
(Development of Internal Genitalia - Female)
- Mesonephric ducts degenerate
* Paramesonephric ducts develop forming fallopian tubes
What does WNT4 regulate?
Development of Internal Genitalia - Female
WNT4 (ovary-determining gene):
- Up-regulates DAX1, which inhibits the function of SOX9
- Regulates the expression of other genes responsible for ovarian differentiation, but many target genes haven’t been identified
What does oestrogen stimulate?
Development of Internal Genitalia - Female
Stimulates the paramesonephric ducts to develop into the female internal genitalia
What is the hormonal control of the development of the female internal genitalia?
In absence of any hormones Wolffian ducts degenerate and Mullerian ducts develop forming fallopian tubes
WNT4 (ovary-determining gene) actions:
- Upregulates DAX1, which inhibits the function of SOX9, preventing the male program
- Regulates the expression of other genes responsible for ovarian differentiation
Oestrogen stimulates the Mullerian ducts to develop into female internal genitalia.
Summary: Medullary cords degenerate and cortical cords develop
What does the lower vagina form from?
Development of Internal Genitalia - Female
Paramesonephric tubercle (a region called the sinovaginal bulbs)
What forms the vaginal plate?
Development of Internal Genitalia - Female
2 evaginations grow out from the pelvic side and proliferate
When is vaginal outgrowth complete and expand around the end of the uterus?
By 20 weeks
Development of female internal genitalia?
- The lower vagina forms from the paramesonephric tubercle (a region called the sinovaginal bulbs)
- Two evaginations grow out from the pelvic side and proliferate forming the vaginal plate
- By 20wks vaginal outgrowth is complete and expands around the end of the uterus
What structures are bipotent?
Development of External Genitalia
Gonads and external genitalia
What determines the path which external genetalia takes in development?
(Development of External Genitalia)
Presence (male) or absence (female) of androgens
Disorders of chromosomal sex
- Chromosomal abnormalities can cause inappropriate gonadal development
- Can have further effects on body development
- Turner - XO (ovary)
- Triple X -XXX (ovary)
- Klinefelter - XXY (testis)
- XYY - XYY (testis)
- Sex reversed - XX (SXR)
- all have 44 autosomes
What is effect of Turner syndrome?
Disorders of Chromosomal Sex
- (45, X0)
- Affects 1 in 2,000 female births
- Oocytes (female germ cells) degenerate since two “X” chromosomes are needed for full ovarian development – leading to “Streak ovary”
- Deficiency in ovarian steroids
- Lack of secondary sex characteristics and infertility
- Other developmental defects: short stature, webbed neck and skeletal deformities
What is Klinefelter Syndrome?
Disorders of Chromosomal Sex
- (47, XXY)
- Develop male phenotype
- Incomplete virilisation and breast enlargement after puberty
- Small testes with decreased spermatogonia
Disorders of Sexual Differentiation?
- Pseudo-hermaphroditism
- Androgen-Insensitivty Syndrome
- Congenital Adrenal Hyperplasia
What is pseudo-hermaphroditism?
- Individual with gonads appropriate to their genotype but external genitalia of the opposite sex
- Abnormality in endocrine signalling between the gonads and developing tissues
- One such syndrome is Androgen-insensitivity Syndrome (previously called testicular feminization syndrome)
- Individuals have a 46, XY karyotype
What is androgen-insensitivity syndrome?
- Testes are initially normal but the tissues lack (or have a dysfunctional) androgen receptor so are unable to respond to testosterone
- The mesonephric ducts degenerate without the support of androgens (unable to sense the signal)
- The testes secrete normal amounts of AMH, so female ducts degenerate – NO DUCTs at all
- Female external genitalia develops but have undescended testes
What is congenital adrenal hyperplasia?
• Genotype is XX and ovaries develop
• However, foetal adrenals are over-active
• Secrete large amounts of steroid hormones some of which
have androgenic action
• Causes development of mesonephric ducts and formation of male external genitalia
• No AMH is secreted therefore female ducts persist – Therefore BOTH ductal systems are present
