12) Sex Differentiation Flashcards
What is the common primordium for external genitalia?
Urogenital sinus
What does the Mullerian duct become? Which sex possesses the Mullerian duct?
- Females
- Oviduct, uterus, upper vagina
What does the urogenital sinus become in females?
Clitoris, vulva
What does the urogenital sinus become in males?
Penis, scrotum
What does the Wolffian duct become? Which sex possesses the Wolffian duct?
- Males
- Epididymis, vas deferens, seminal vesicle
The removal of undifferentiated testes from male rabbit embryos produced what type of reproductive tract and genitalia?
- Female reproductive tract
- Female genitalia
What type of reproductive tract and genitalia is produced from gonadectomised female embryos?
Female features
The testes are (necessary/not necessary) for male sexual differentiation.
necessary
The ovaries are (necessary/not necessary) for female sexual differentiation.
not necessary
The development of male features is hormone (dependent/independent).
dependent
The development of female features is hormone (dependent/independent).
independent
Is the development into a male or female the default pathway?
Female
What are the three pre-requisites for normal sex differentiation?
1) Normal intact chromosome complement
2) Fully functioning sex determination genes
3) Intact steroidogenic pathway and receptors
Why is sexual differentiation required in males?
Provision of sperm
Why is sexual differentiation required in females?
- Provision of eggs
- Internal fertilization
- Pregnancy
- Lactation
How are males and females different in terms of their chromosomes?
- Males: XY
- Females: XX
True or False: the presence of the Y chromosome always produces a male phenotype.
True
What is Klinefelter syndrome? What are symptoms?
- Two or more X chromosomes in males
- Sterility and small testicles
What is Turner syndrome? What are symptoms?
- A female is partly or completely missing an X chromosome (XO)
- Short stature, loss of ovarian function
Normally, chromosomes pair and cross-over at which sections?
They cross-over along ALL their length
How do X and Y chromosomes pair?
Y pairs with X only at one end (pairing region)
How do X and Y chromosomes cross-over?
There are RARELY crossing-over events between X and Y
What does the sry gene stand for?
Sex-determining region of the Y chromosome
Is the SRY gene retained in the pairing or non-pairing region?
In the non-pairing region of the Y chromosome
What occurs when the SRY gene is mis-paired, and transferred to the X chromosome?
- Sperm produces an X chromosome with the SRY gene
- Fertilization by the sperm would produce an XX male
What occurs if the SRY gene is deleted or mutated in the Y chromosome?
Produces an XY female
23/24 of the mutations causing an XY female lie in which region?
DNA-binding domain (HMG box) of the SRY gene
An amino acid region of the SRY gene shows homology to a motif within the _______ proteins, which possesses DNA-binding activity.
high mobility group (HMG)
Is DAX1 contained on the X or Y chromosome? What is its function?
- X chromosome
- Inhibits testicular development
What genes does the SRY gene inhibit?
- WNT4
- DAX1
The expression of SRY leads to the expression of other genes, leading to ____.
AMH
What is AMH? What produces AMH?
- Anti-mullerian hormone (Mullerian-inhibiting substance)
- Produced by Sertoli cells
The differentiation of the gonad by what genes results in Sertoli cells producing AMH, and Leydig cells producing testosterone?
- SRY
- SOX9
- SOX3
How does testosterone affect the Wolffian duct?
Positive effect on the development of the Wolffian duct
Which component allows for the development of male external genitalia?
Dihydroxytestosterone (DHT) produced from testosterone
Which component allows for the development of female external genitalia?
The lack of DHT from the lack of testosterone
What is responsible for testicular descent?
Testicular hormones
What guides testicular descent?
Gubernaculum
What hormone allows for trans-abdominal descent of the testes?
AMH
What allows for inguino-scrotal descent of the testes to the scrotal position?
Testosterone
How does the gubernaculum guide testicular descent?
- The gubernaculum swells, providing traction to the testes to pull them through the inguinal canal
- The testes are pulled to the outside of the body
- The gubernaculum shrinks and the inguinal canal seals
What are the effects of defects in testosterone synthesis or actions? (3)
1) Phenotypic female (XY)
2) No ovaries (testes, but infertile)
3) Blind-ending vagina
What is the cause of androgen-insensitivity syndrome? What are symptoms?
- A lack of androgen receptors
- Lack of epididymis, vas deferences, presence of female external genitalia
What are possible causes for defects in testosterone synthesis or action?
- StAR protein deficiency
- Leydig cell hypoplasia
- Deficiency in 17-hydroxylase, 17-lyase
Do individuals with androgen-insensitivity syndrome possess testes?
- Yes, but they are contained within the abnominal cavity (cryptorchidism)
- The gubernaculum cannot shrink, and the testes can’t be pulled through the inguinal canal
What is the treatment for androgen-insensitivity syndrome?
- Surgery to correct the ambiguous genitalia
- Gonadectomy post-puberty
How does the quantity of aromatase differ in individuals with androgen-insensitivity syndrome?
High levels of aromatase
What is the effect of congenital adrenal hyperplasia?
- Hyperplasia of the adrenal glands before birth, causing excessive androgen production
- Masculinization of the external genitalia at birth
What is the most common defect in CAH?
21-hydroxylase deficiency
What are the effects of a deficiency in 21-hydroxylase? (3)
1) Low cortisol and aldosterone production
2) Reduced negative feedback onto the hypothalamic/pituitary axis
3) Increased androgen production
What allows for the sexual differentiation of the brain?
- Testosterone is converted to estrogen by aromatase
- Estrogen binding to its receptor in the brain causes sexual differentiation
When does sexual differentiation of the brain occur? How does it vary among species?
- Occurs during a “critical time period” during development
- The timing is variable by species
When does sexual differentiation of the brain occur in primates?
3 to 6 months pre-natally
What is the effect of gonadal steroids on the “indifferent” brain?
Masculinization
How may sexual differentiation of the brain affect structure and function?
- Affects the propensity of psychiatric diseases
- Differences in brain activity patterns (apparent over wide range of cultures)
What is the effect of CAH on child play patterns? Why?
- Tendency towards male play patterns
- Exposure to androgens in utero
Which center controls LH and FSH in males post-puberty?
Tonic center
Do males possess a surge center?
No, the surge center is defeminized and does not develop
Does testosterone freely enter the brain? Does estrogen?
- Testosterone: yes (converted to estradiol)
- Estradiol: no
What occurs to estradiol produced by the fetal ovary?
Binds to alpha-fetoprotein
Which center controls LH and FSH in females post-puberty?
Surge center AND tonic center
What are the two functions of the gonads?
1) Gametogenesis
2) Hormonogenesis
What are the three functional outcomes of hormonogenesis?
1) Electrolyte homeostasis
2) Fuel and protein metabolism
3) Adiposity and muscle mass
The sex determination of the fetus requires the hypothalamic-pituitary-gonadal axis in which sex?
- Required in males
- Not required in females
Sexual changes in puberty requires the hypothalamic-pituitary-gonadal axis in which sex?
Important in BOTH sexes
What is required for reproduction in females?
Sex hormones during pregnancy and parturition
Does menopause or andropause require the hypothalamic-pituitary-gonadal axis?
Important in BOTH sexes
How does testosterone vary during the fetal period? What is the function?
- Rise in testosterone
- Associated with sexual differentiation
How does testosterone vary during the neonatal period? What is the function?
- Rise in testosterone
- Function is unknown