15-03-23 - Sex Determination and Development of the Reproductive System Flashcards
Learning outcomes
- Describe the influence of genes on differentiation of the reproductive system.
- Explain how the gonads initially develop with bipotential
- Summarise how the gonads undergo sexual dimorphic differentiation
- Describe the development/differentiation of the internal genitalia
- Explain the development of the external genitalia
- Describe how genetic and endocrine abnormalities can influence sexual differentiation.
What is the purpose of sexual reproduction?
What is required for sexual reproduction to occur?
What does fertilization re-establish?
- Human sexual reproduction creates genetic variation in offspring, which can be useful for adapting to changing or challenging environments
- Some gene variants may become advantageous in the future under some environmental constraint/insult
- Sexual reproduction requires formation of sperm and oocytes that are haploid, and fertilization re-establishes the diploid state after which chromosomal (Chr) sex is determined
What is sexual differentiation?
What is sex determination?
What will happen if the developing tastes are removed before sexual differentiation?
What drives the sexual differentiation of the reproductive tracts?
What additional structures are needed in the female reproductive tract?
- Sexual differentiation is the process by which male and females become structurally and functionally dissimilar.
- The term sex determination is used to describe the initiation of the male differentiation pathway
- If the developing testes are removed before sexual differentiation, then female differentiation ensues
- The development of sexually differentiated gonads drives further sexual differentiation of the reproductive tracts
- Specialized structures of the female reproductive tract are needed to nurture the growing embryo and infant after birth
How many chromosomes are there in human somatic cells?
What chromosomes do females and females have?
What us produced by germ cells during meiosis?
How many chromosomes do oocytes and spermatozoa have?
- Human somatic cells have 22 pairs of autosomes and 1 pair of sex Chromosomes (XX or XY)
- Female (46, XX) – homogametic
- Male (46, XY) – heterogametic
- During meiosis germ cells produce gametes with half the number of chromosomes (haploid)
- Oocytes are 23, X
- Spermatozoa are 23, X or 23, Y
What is the genetic determinant of sex?
What occurs once gonadal differentiation starts?
How is DNA structured on the Y chromosome?
Where are many of the genes required for testes development located?
- The genetic determinant of sex is the presence or absence of the Y chromosomes
- Y Chromosome leads to male gonads (testes)
- Absence of Y chromosome leads to female gonads (ovaries)
- Once gonadal differentiation starts, the developing gonad directs further processes that produce sexual dimorphism
- The Y chromosome is small and most of its DNA is condensed
- Many of the genes required for testes development are located on autosomes or on the X Chromosome
What is SRY?
What is its role?
What is the term sex determination used to describe?
What occurs once gonadal differentiation is initiated?
- SRY is a gene that encodes a transcription factor that regulates the expression of genes on other chromosomes
- SRY turns on genes responsible for testes differentiation and turns off ovarian genes
- The term sex determination is used to describe the initiation of the male differentiation path by the SRY gene
- Once gonadal differentiation is initiated, gonadal hormones then promote sexual dimorphic development of the reproductive tract
What are gonads derived from?
How do Primary (primitive) sex cords form?
Up until what week are the gonads identical in both sexes?
- Gonads are derived from the gonadal ridge (genital ridge), pair of longitudinal ridges, on the medial side of the mesonephros
- Primary (primitive) sex cords form by proliferation of the surface epithelial cells that penetrate the underlying mesenchyme
- The gonads are identical in both sexes until the 7th week of development (indifferent gonads)
What do primordial germ cells (PGCs) originate from?
Where and when are they first identifiable?
How many primordial germ cells initially appear?
When do they undergo mitotic divisions?
When do they migrate into the genital ridge?
- Primordial germ cells (PGCs) originate from epiblast-derived cells and are first identifiable in the wall of the yolk sac (~3 weeks)
- ~10 primordial germ cells first appear but undergo mitotic divisions en route to the genital ridge (~2000 arrive)
- They migrate into the genital ridge (5th week) driven by chemotaxis
What do the PGCs do by week 6?
What is the influence of PGCs on the developing gonad?
What is the path of development determined by?
- By week 6, the PGCs invade the gonadal ridges and are closely associated with the primitive sex cords
- The influence of PGCs on the developing gonad is sexually dimorphic: PGC progression through meiosis is essential for the maintenance of the foetal ovary, otherwise prospective follicular cells degenerate, leading to streak ovaries, but testes development is not hindered by lack of germ cells
- The path of development is determined by the presence of Y chromosome (SRY)
Gonadal Differentiation – Male.
What occurs in the 7th week of development in males?
How do Sertoli and Leydig cells form?
How does the rete testis cord form?
- Gonadal Differentiation – Male
- In 7th week (under influence of SRY), primitive sex cords proliferate and penetrate the medulla forming “medullary” testis cords
- Mesodermal cells differentiate into Sertoli cells in the cords under influence of SRY, they aggregate and enclose germ cells
- Testis cords become looped –contact with the ingrowing mesonephric tubule forming Rete testis cords
Gonadal Differentiation – Female. What occurs in female development at week 7.
What do cortical cords form from?
How do primordial follicles form?
What are germ cells definitely required for?
- Gonadal Differentiation – Female
- Female development at week 7 - the absence of SRY leads to degeneration of medullary/primitive sex cords
- Cortical cords form from proliferating surface epithelium forming distinct cell clusters
- Epithelial cells proliferate around each oogonium (germ cell) – forming primordial follicles
- Germ cells are absolutely required for the formation of the ovarian follicles
Formation of Genital Ducts.
What occurs in the embryo at weeks 7-8?
Which ducts give rise to which ductal systems?
What does the developmental path taken depend on?
- Formation of Genital Ducts
- At 7-8 weeks embryos 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 testis not the ovary
Describe the flowchart for the Genetic control of genital duct development
Development of Internal Genitalia – Male.
What triggers the differentiation of Sertoli and Leydig cells?
What do each of these cells secrete/express?
What is the remnant of the female reproductive system left in males?
What occurs after descent of the testes?
What forms the efferent ductules?
What forms the epididymis?
What forms the vas deferens and seminal vesicles?
- Development of Internal Genitalia – Male
- Up to 16 weeks
- SRY activates SOX-9, which triggers the differentiation of Sertoli and Leydig cells of the testes
- Leydig cells start to secrete testosterone at week 8, which leads to further development of internal male genitalia
- Sertoli cells express antimullerian hormone, leading to the regression of the paramorphic ducts, and leaves the paramesonephric tubercle as a remnant of the female reproductive system
- After testes descent
- After descent, there is further differentiation
- The epigenital tubules form the efferent ductules later on
- The paragenital tubules form the epididymis later on
- The mesonephric duct forms the vas deferens and seminal vesicles
Development of Internal Genitalia – Female.
What occurs in the absence of the SRY gene and androgens?
What do the paramesonephric ducts form?
What is there left in the female reproductive system of the male reproductive system?
- In the absence of the SRY gene and androgens, the mesonephric ducts start to degenerate at 8 weeks
- The paramesonephric ducts later develop and differentiate into the female genitalia, forming the fallopian tubes, uterus, and upper vagina
- The Epoophoron is left as a remnant of the male reproductive system
Development of Internal Genitalia – Female.
What does the lower vagina form from?
How does the vaginal plate form?
What has occurred by 20 weeks?
- Development of Internal Genitalia – Female.
- 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 weeks, vaginal outgrowth is complete and expands around the end of the uterus
How are the gonads and external genitalia similar?
How is the developmental path of external genitalia determined?
Describe the 4 steps in the development of male external genitalia?
Describe the 5 steps in the development of female external genitalia?
- Like gonads, external genitalia are initially bipotent
- Developmental path if the external genitalia taken depends on the presence or absence of androgens
- 4 Steps in the development of male external genitalia
1) Androgens present (DHT)
2) Genital tubercle forms gland
3) The urethral groove forms, which will form the urethra
4) The genital swellings will develop into the scrotum - 5 steps in the development of female external genitalia:
1) No androgens present (default)
2) Genital tubercle forms clitoris
3) The urogenital sinus become the urethral groove, which remains open and will form the vaginal orifice
4) The urethral folds from the labia minora
5) Genital swellings form the labia majora
What can chromosomal abnormalities cause?
What are the chromosomes of someone with Turner Syndrome?
What number of female births are affected by Turner Syndrome?
What 6 effects do we see in females with Turner Syndrome?
- Chromosomal abnormalities can cause inappropriate gonadal development, which can have further effects on body development
- Turner Syndrome (45, X0 – missing an entire X chromosoem) affects 1 in 2,000 female births
- 6 Effects we see in females with Turner Syndrome:
1) Deficiency in ovarian steroids
2) Lack of secondary sex characteristics (breasts, pubic hair)
3) Infertility
* Oocytes (female germ cells) degenerate since two “X” chromosomes are needed for full ovarian development – leading to a “Streak ovary”
* This means there will be no viable follicles, causing infertility
4) Short stature
5) Webbed neck
6) Skeletal deformities
What are the chromosomes of those with Klinefelter Syndrome.
What are 3 effects seen in those with Klinefelter Syndrome?
- Those with Klinefelter Syndrome have 47, XXY chromosomes
- 3 effects seen in those with Klinefelter Syndrome:
1) Develop male phenotype
2) Incomplete virilization and breast enlargement after puberty
3) Small testes with decreased spermatogonia
What chromosomes lead to sex-reversed syndrome?
How does this affect gonadal development?
What are the chromosomes of someone with sex reversed syndrome?
- Sex reversed syndrome is seen in those with XX chromosomes where the SRY gene has been translocated onto an autosome (non-sex) or X chromosome
- This will promote differentiation down the male pathway and lead to the development of male gonads
- Those with sex reversed syndrome have chromosomes 44, XXSXR)
Sex chromosomes disorders summary
What causes Androgen-Insensitivity Syndrome?
What happens to the mesonephric ducts?
What happens to mullerian ducts?
What genitalia develops in Androgen-Insensitivity Syndrome?
- In those with 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 (male) degenerate without the support of androgen signalling (unable to sense the signal)
- The testes secrete normal amounts of AMH (anti-mullerian hormone), so female mullerian (paramesonephric) ducts degenerate, leading to there being no ducts at all
- In Androgen-Insensitivity Syndrome, female external genitalia develops but there is also undescended testes
DSD – Congential Adrenal Hyperplasia (CAH).
What is the genotype in those with CAH?
What gonads develop?
How does male genitalia also develop?
Which ductal systems develop in CAH?
What scale can be used to assign sex?
- DSD – Congential Adrenal Hyperplasia (CAH)
- The Genotype in those with CAH is XX and ovaries develop
- In CAH, foetal adrenals are over-active and secrete large amounts of steroid hormones some of which have androgenic action
- This 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
- The prader scale (in picture) can be used to assign gender
Summary of Sexual Differentiation flowchart
Summary of Sexual Differentiation flowchart
