Development of the Reproductive System and Sex Determination Flashcards
Why is sexual reproduction advantageous ?
- Sexual reproduction creates genetic variety, which in turn is useful for adapting to constantly changing and challenging environments
- Some gene variants may become advantageous in the future under some environmental constraint or insult
What are the requirements of sexual reproduction ? What is the result of sexual reproduction ?
- Sexual reproduction requires formation of sperm and oocytes that are haploid
- Fertilization re-establishes the diploid state and chromosomal sex is determined
Define sexual differentiation.
- Process by which male and females become structurally and functionally dissimilar.
- If the developing testes (or ovaries) are removed before sexual differentiation, then female differentiation ensues.
- The development of sexually differentiated gonads drives further sexual differentiation of the reproductive tracts
Define sexual determination.
The term sex determination is used to describe the initiation of the male differentiation pathway by SRY.
What is the aim of specialised structures of the female reproductive tract ?
Specialized structures of the female reproductive tract are needed to nurture the growing embryo and infant after birth.
Describe the chromosomal composition of human somatic cells.
Human somatic cells have 22 pairs of autosomes and 1 pair of sex chromosomes (XX or XY)
Distinguish between males and females’ chromosomes.
- Female (46, XX) – homogametic
* Male (46, XY) – heterogametic
Identify the end result of meiosis of germ cells.
During meiosis germ cells produce gametes with half the number of chromosomes (haploid):
• Oocytes are 23, X
• Spermatozoa are 23, X or 23, Y
How can we distinguish between male and female karyotype visibly ?
Male, XY (X smaller than Y)
Female, XX
Identify the genetic determinant of sex.
The genetic determinant of sex is the presence or absence of the Y chromosome;
• Presence of “Y” Chrom à male gonads (testes)
• Absence of “Y” Chrom à female gonads (ovaries)
Which chromosomes do not impact gonad differentiation ?
Autosomes or “X” chromosomes do not normally influence gonad differentiation
Once gonadal differentiation is initiated by the presence or absence of the Y chromosome, what controls further sexual events ?
Once gonadal differentiation is initiated, the developing gonad directs further developmental events that produce sexual dimorphism
Describe the structural feature, and genes present of the Y chromosome.
The Y chromosome is 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
Which chromosomes are involved with testes development ?
Y chromosome encodes only few genes involved with testes development.
Many of the genes required for testes development are located on autosomes or on the X chromosome. Instead, Y chromosome has a regulatory gene that controls these other developmental genes and so indirectly controls the formation of testes.
How was the location of the regulatory gene on the Y chromosome that controls other developmental genes on the X chromosome and autosomes, and so indirectly controls the formation of testes.
The location of this regulatory gene was established in animal studies and by studying subjects with genetic abnormalities.
E.g. Phenotypic women with “XY” genotypes or phenotypic men with “XX” genotypes
What happens, to the chromosomes of an XY female ?
Part of the short arm of the Y chromosome is missing or mutated in XY females (due to non-disjunction)
This region contains a gene known as SRY (Sex-determining region of the Y chromosome).
What happens to the chromosomes of an XX male ?
XX males have a section of the Y chromosome translocated to an autosome or X chromosome (due to non-disjunction)
This region contains a gene known as SRY (Sex-determining region of the Y chromosome).
Given that X and Y chromosomes are different, how can they pair ?
Because the Y chromosome retains regions of homology with the X chromosome that permits pairing during meiosis but errors can occur called non-disjunction
Describe the function of the SRY gene. What happens following SRY’s action ?
SRY – encodes a DNA binding protein (transcription factor) that regulates expression of genes on other chromosomes responsible for testes differentiation.
Once gonadal differentiation is initiated, gonadal hormones trigger the cascades that produce sexual dimorphic development of the reproductive tract
Identify the steps of gonadal differentiation which are common to both genders.
• Primordial germ cells (PGCs) originate from the epiblast and are first identifiable in the wall of the yolk sac (~2 wks)
• ~10 primordial germ cells first appear but undergo mitotic divisions en route to the genital ridge (~2000 arrive)
• They migrate into the genital ridge driven by chemotaxis
—–
• By 6 wks the PGCs invade the genital ridges and become surrounded by the primitive medullary sex cords
• If the migration of PGCs fails to enter the genital ridge the gonads do not develop
• PGCs have an inductive influence on development of the gonad into ovaries and testes but no role driving sexual dimorphism
• The path of development is determined by the presence of Y chromosome (SRY)
Which cell types do ovaries and testes develop from ?
• Testes and ovaries form from two distinct cell types
– Somatic mesenchyme (immature unspecialised CT)
– Primordial germ cells (cells destined to be
How long are male and female gonads identical ?
• Gonads are identical in both sexes until the 7th wk of dev (indifferent gonads)
Describe the steps of gonadal differentiation in the male (AFTER steps common to both).
1) Under the influence of the SRY gene, primitive sex cords proliferate and penetrate the medulla forming testis cords
2) Testis cords become looped –contact with the ingrowing mesonephric tubule called Rete testis
3) Primordial germ cells come to reside within the developing testis cords
4) Mesodermal cells differentiate into Sertoli cells in the cords
5) Mesenchyme tissue in interstitial spaces develop into Leydig
cells and start to secrete testosterone by the 8th wk
6) Testosterone then influences the development of the genital ducts and external genitalia
7) By 20 wks, the testis cords are horseshoe-shaped, composed of germ cells and Sertoli cells
Describe the steps of gonadal differentiation in the female (AFTER steps common to both).
1) Female development (past 6th week) due to the absence of Y chromosome, leads to degeneration of medullary cords/primitive sex cords
2) Cortical cords form from proliferating surface epithelium forming distinct cell clusters around germ cells by 12 wks
3) Cells proliferate and surround each oogonium (germ cell) with epithelial layer of follicular cells – forming primordial follicles
4) Germ cells are absolutely required for the formation of the ovarian follicles
Describe the steps of genital ducts formation.
• At 7-8 wks embryos acquire dual ductal systems that are precursors to the male and female internal genitalia
• Wolffian (mesonephric) (connected to mesonephros, of developing kidney) ducts give rise to the male genital ductal system
• Müllerian (paramesonephric) (connected to urogenital sinus) ducts give rise to the female genital ductal system
(both^ of these present in indifferent stage)
• The developmental path taken depends on hormones secreted by the developing testis NOT the ovary
Describe the steps in the development of the male internal genitalia.
1) In males, SRY acts in conjunction with other transcription factors such as SOX9 and SF-1 to stimulate the differentiation of Sertoli and Leydig cells
2) Sertoli cells then express anti-Müllerian hormone (AMH) which leads to regression of the Müllerian/paramesonephric ducts and prevents development of female structures
3) Leydig cells start secreting testosterone which supports the the development of the mesonephric ducts and leads to virilisation
After testes descent:
- Paramesonephric ducts have regressed, remnant is paramesonephric tubercle (all that’s left of female duct system)
- Epigenital tubules develop and contact with the cord of testes. Later form the efferent ductules.
- Mesonephric duct becomes highly convoluted, forming epididymis.
- Rest of mesonephric duct obtains thick muscular coat and becomes vas deferens and seminal vesicle.
Describe the steps in the development of the female internal genitalia.
After ovarian descent:
• In absence of any hormones mesonephric ducts degenerate and paramesonephric ducts develop forming fallopian tubes
• WNT4 (ovary-determining gene) up-regulates DAX1, which inhibits the function of SOX9, preventing the male program
• WNT4 also regulates the expression of other genes responsible for ovarian differentiation, but many target genes have not been identified
• Estrogen stimulates the paramesonephric ducts to develop into the 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 20 wks, vaginal outgrowth is complete and expands around the end of the uterus
Describe the state of the cortical, and medullary cord in the male, and female.
MALE
- No cortical cords
- Medullary cords develop
FEMALE
- Cortical cords develop
- Medullary cords degenerate
Are external genitalia unipotent, or bipotent initially ?
External genitalia initially bipotent
What is the developmental path taken by external genitalia (male or female) dependant on ?
Developmental path taken depends on the PRESENCE or ABSENCE of androgens
- Presence of androgens = MALE
- Absence of androgens (default) = FEMALE
What type of problem can result in inappropriate gonadal development ?
Chromosomal abnormalities can cause inappropriate gonadal development (and also can have further effects on body development)
Identify the main disorders of chromosomal sex.
- Turner’s Syndrome (45, X0)
- Klinfelter Syndrome (47, XXY)
- Triple X Syndrome (47, XXX)
- XYY Syndrome (47, XYY)
- Sex reversed
Describe the main features of Turner’s Syndrome.
(45, X0)
- 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
State the number of autosomes, sex chromosomes, and gonads in each of the following:
- Turner’s Syndrome
- Klinefelter Syndrome
- Triple X Syndrome
- XYY Syndrome
- Sex reversed
- Turner’s Syndrome: 44 autosomes, XO, ovary
- Klinefelter Syndrome: 44 autosomes, XXY, testis
- Triple X Syndrome: 44 autosomes, XXX, ovary
- XYY Syndrome: 44 autosomes, XYY, testis
- Sex reversed: 44 autosomes, XX(SXR), testis (translocation of SRY gene on autosome or X chromosome, meaning testes develop)
Describe the main features of Klinefelter’s Syndrome.
- Develop male phenotype
- Incomplete virilization and breast enlargement after puberty
- Small testes with decreased spermatogonia
What defect occurs if the sex chromosomes are XXY or XXX with 66 autosomes ? Which gonads would each of these yield otherwise ?
Triploidy (not viable)
XXX: ovary
XXY: testis
Identify disorders of sexual differentiation (DSD).
- Pseudo-hermaphroditism
- Androgen-Insensitivity Syndrome
- Congenital Adrenal Hyperplasia
Describe the main features of 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
Describe the main features of 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
Describe the main features of 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
Summarise sexual differentiation.
Refer to diagram on slide 44 of lecture slides.
Identify the female internal genitalia.
vagina, uterus, Fallopian tubes, and ovaries.
Identify the male internal genitalia.
seminal vesicle, testes, vas deferens, epididymis, prostate, bulbourethral gland, and ejaculatory duct.
Identify the male external genitalia.
penis, urethra, and scrotum.
Identify the female external genitalia.
Mons pubis Labia majora Labium minora Clitoris Vaginal vestibule Hymen Vestibular bulbs Greater vestibular gland
