reproduction 1 Flashcards
Structure of reproductive system in both sexes
- Gonad (e.g. testes/ovaries)
⇒ Produce gametes and secretory glands - Internal genutalia
⇒ Reproductive tracts and secretiry glands - External genitalia (e.g. vagina and clitoris)
What does the mullerian duct and wolffian duct develop into after sex determination
The mullerian duct ⇒ Fallopian/uterine tube
Wolffian duct ⇒ Vas deferens
What are the 3 levels of sex defined as?
Genetic sex
Gonadal sex
Phenotypic sex
How does genetic sex determine gonad sec
In the Y chromosome of an XY human, the Sex-determining Region of the Y gene (SRY gene) encodes the SRY protein/Testis-Determining Factor (TDF) in the bi-potential gonads
⇒ Primitive (bipotential) gonads differentiate into testes
- SRY-BOX Transcript factor 9 (SOX9) is an important gene for sex determination
- Fibroblast Growth Factor 9 and steroidogenic factor 1 are also involved in sex determination
Functions of SOX9
- Mediates the effect of SRY
- Direct target of SRY, a TF that promotes the expression of SOX9
- SOX9 mutation is associated with male-female reversal in human and mice
⇒ sex reversal following the deletion of a single distal enhancer of SOX9 - SOX9 induces testis development and male behaviour in XX human and transgenic (genetically modified) mice
⇒ Only at high levels of SOX9
What are some examples or reasons why R-Spondin-1 (RSPO1) drives ovary development
- XX humans display male gonad and phenotypic sex due to loss of function mutation in RSPO1
- A 46XY human with duplication of chromosome 1 region containing RSPO1 had a male-to-female sex reversal
⇒ Too much expression of RSPO1 → drives ovary development in XY human ⇒ female behaviour - Similar sex reversals were observed in transgenic (genetically modified) mice
- R spondins signal to β catenin (when binded to lipoprotein receptor-related proteins (LRP))
How is gonad determination an antagonistic balance between SRY and β-catenin signaling
Proteins and genes that determine 1 sex inhibit the expression of genes, which determine the other sex
Production of SOX9 inhibits the effect of FoxI2 and Wnt4/RSPO1 to promote the development of testis
Production of Wnt4 and RSPO1 sends the signal to β-catenin
β-catenin and FoxI2 inhibit the effect of SOX9 and Fgf9 to promote development kf ovaries
How do the testes determine phenotypic sex?
After gonad is differentiated to form testes, the testes secrete:
- Anti-mullerian hormones, which results in:
→ Degeneration of mullerian ducts
→ Prevent ovary development
- Testosterone, which results in:
→ Wolffian ducts develop into male reproductive tracts
→ Seminal vesicles and urogenital sinus into prostate
→ Does not cause mullerian degeneration
*SRY/SOX9 level must be high for wolffian duct to develop fully (refer to grafted testis in female infant)
Drop in exposure of maternal estrogen at birth results in ___ production of ___ and other reproductive hormones in the infant
⇒ ___ activation of the ___-___-___ axis
(copy paste and fill in the blank)
Drop in exposure of maternal estrogen at birth results in increased production of gonadotropins and other reproductive hormones in the infant
⇒ Transient activation of the hypothalamic-pituitary-gonadal axis
Disorders of chromosomal sex (got 5)
Turner’s syndrome: 44 + XO (not entirely compatible with survival — female, 1 in 2500
⇒ Wedged neck, short statue
45XO / 46XY mosaicism (XO/XY) — 1 in 15000 (either XO/XY makeup)
Triple X female (44+XXX) — 1 in 1000, infertile (intellectually disabled)
Klinefelter syndrome: at least 1 extra X (44+XXY/44+XXXY) chromosomes — male, 1 in 1000, infertile (primarily affects the testes)
Jacobs syndrome (XYY) — 1 in 1000 male births, 96% phenotypically normal, some infertile, intellectually disabled
Disorders of phenotypic sex due to endocrine disorders (got 3)
Defect in androgen/androgen receptors
- Testes in genetic male fail to secrete androgens
⇒ Results in the development of apparent anatomic female in a genetic male
⇒ No sex drive / spermatogenesis
- Defect in the androgen receptor gene
⇒ Testicular feminization syndrome/androgen insensitivity syndrome
Genetic deficiency of 5α-reductase
- Failure of development of male external genitalia
-5α-reductase is used to convert testosterone to dihydrotestosterone, which has a higher affinity with androgen receptors than testosterone (by 4 times)
Adrenal androgen hypersecretion may cause genital ambiguity in female infant
- Congenital adrenal hyperplasia
- e.g. development of micropenis
The accessory sex glands of the male reproductive system include seminal vesicles, prostate glands, bulbourethral glands, the testes, and the interstitial cells/Leydig cells. What are the functions of these cells?
Seminal vesicle
- Provide the bulk of the semen
- Supply fructose to nourish the sperm
- Secrete peostaglandins to stimulate the contracttion of the smooth muscles of the ‘tract’ to facilitate sperm transport
- Secrete fibrinogen to clot the semen → when in the vagina ⇒ prevent outflow of semen from the vagina
Prostate gland
- Secrete alkaline fluid to neutralise the acidic vaginal secretion
- Provide clotting enzymes to clot the semen
- Provides fibrinolysis to degrade the clot → for mobilisation during ffertilisation
Bulbourethral glands
- Secrete mucus for lubrication
The testes:
Seminiferous tubule
- Contains germinal cells (spermatogenesis cells at different stages) and sertoli cells
- Site of spermatogenesis (sperm cell production)
Interstitial cells/Leydig cells
- Secretes testosterone
What are the functions of sertoli cells (got 6)
Form tight junctions to provide testes-blood barrier
⇒ Protect from damages and external chemicals
Produce chemicals and proteins to nourish spermatogenic cells
⇒ Which may be lacking in a Y chromosome expression
Establish stem cell niche to ensure renewal of sperm cell precursors
Produce androgen-binding protein (ABP) which binds to testosterone
→ To concentrate high levels of the hormones in the tubule
Secretes inhibin to inhibit FSH release
Secretes anti-mullerian hormones (AMH)
⇒ Anti-female reproductive tract development
Spermatogenesis
Symmetric division of ___ during pre-puberty
___ division ⇒ to produce/maintain sperm cells
Spermatids are connected by ___ bridge
- Incomplete ___
- To support each other
⇒ Generate enough protein for survival
- The secondary spermatocytes are also linked by the ___ bridge
Only when needed, spermatids undergo ___ and is packaged to form ___ (sperm cells) (copy paste and fell in the blank)
Spermatogenesis
Symmetric division of spermatogonium during pre-puberty
Asymmetric division ⇒ to produce/maintain sperm cells
Spermatids are connected by cytoplasmic bridge
- Incomplete cytokinesis
- To support each other
⇒ Generate enough protein for survival
- The secondary spermatocytes are also linked by the cytoplasmic bridge
Only when needed, spermatids undergo cytokinesis and is packaged to form spermatozoa (sperm cells)
Androgens, site of synthesis, and its target tissue
Includes adrenal and testicular androgens
Testosterone is synthesised by Leydig cells (interstitial cells)
Testosterone is converted to dihydrotestosterone (DHT) in some target tissues by 5α-reductase ⇒ for the development of male external genitalia
- Target tissues of DHT includes prostate and external genitalia
- Target tissues of testosterone: wolffian ducts, the testes, the bone, muscles, kidneys and brain
Functions of androgens (got 6)
Sexual differentiation
- Induces the development of male reproductive tract and external genitalia
- Promote descending of testes into scrotum
Spermatogensis
- Essential for both meiosis and mitosis
Growth and muturation of the reproductive system
- Maintain the function of the male reproductive tract
Development of secondary sexual characteristics
Male-pattern behaviour
- Regulates sexuality, aggression, cognition, emotion, personality, etc
Non-reproductive functions:
- Signal protein anabolism and muscle development
- Stimulate bone growth and closure of epiphyseal plate
⇒ Start and stop bone lengthening
Function and effects of anabolic steroids (enhancement drugs)
Similar to testosterone (have cholesterol ring)
- Synthetic steroids are similar to testosterone in function
- Targets androgen receptors
- Used for hormone replacement therapy
- Abused for performance enhancement and ‘muscle building’
Negative effects of anabolic steroids
- Short term effects:
→ Males: premature baldness, testicular degeneration, impotence, development of breasts
→ Females: Irreversible masculinising effect, menstrual irregularities, uterine atrophy (decrease in size)
- Long term effects
→ Cardiovascular diseases, increased risk of liver cancer, hostility and aggression
Characteristics of prostaglandins
Chemical messengers produced in virtually all tissues (controversial on whether it’s considered a hormone or not)
- 20-carbon fatty acid derivatives from arachidonics acid
- Act locally and inactivated rapidly after action
- Letters of prostaglandins denote structural variation in the 5-carbon ring
⇒ PGA, PGE, PGF - Number denotes no. of double bonds in the side chains
⇒ PGE1, PGE2
Characteristics of prostaglandins
Chemical messengers produced in virtually all tissues (controversial on whether it’s considered a hormone or not)
- 20-carbon fatty acid derivatives from arachidonics acid
- Act locally and inactivated rapidly after action
- Letters of prostaglandins denote structural variation in the 5-carbon ring
⇒ PGA, PGE, PGF - Number denotes no. of double bonds in the side chains
⇒ PGE1, PGE2
Functions of prostaglandins
Have very broad functions (fever, inflammation, smooth muscle contraction, etc)
Reproductive functions
- Stimulates reproductive tract contraction
⇒ Facilitates sperm transport
⇒ Associated with painful menstruation
⇒ Involved in uterine contrast during labour
Important for ovulation
Prostaglandin synthesis by cyclooxygenase (COX) 1 and 2
COX-1 catalyzes the conversion of arachidonic acid to prostaglandins (prostaglandin H2) stimulating platelet aggregation, gastric mucosa, and the kidney
⇒ Causes damage to the body tissues
→ Use Non-Steroid Inflammatory Drug (NSAID) to treat as it blocks the conversion of arachidonic acids to prostaglandins
COX-2 catalyzes the conversion of arachidonic acid to prostaglandin (prostacyclin and prostaglandin E2), which plays a significant role in tissue inflammation, which can be inhibited by steroids
