Lecture 13: 79 - Reproduction 1 Flashcards
What determines the following:
- Genetic sex
- Gonadal sex
- Genital sex
- Gender sex (behavioral)
- Genetic sex
- identified by karyotype (XX or XY) - Gonadal sex
(set by gene expression - testes or ovaries) - Genital sex
- external genitalia set by HORMONES - Gender sex (behavioral)
- genotype, phenotype hormones, rearing cues, psycho-social factors
What region of the Y chromosome determines whether testes develop?
What hormone carries the androgen receptor?
What does ovary development depend on?
What are some examples of chromosomal abnormalities?
- Sry
-XY mice with no functional Sry develop ovaries
XX mice with added Sry develop testis - X Chromosome
- 2 X and no Y
- Loss of one X chromosome results in ovarian dysgenesis but not loss of female ducts or genitalia - Aneuploidy (XXY), Mosaicism (different genetic makeup), Chimerism (2 embryos fuse w/ different genetic makeup), Structural Errors (the mouse - one part of the chromosome breaks off and goes somewhere else)
- Differentiate between mitosis and meiosis:
Meiosis = haploid gametes
- all different (4)
Mitosis = diploid gametes
- 2 gametes (2n –> 2n) identical
- Mitosis
Involves _____ cells (ex: cut on skin) - Produces ______ daughter cells
- Yes/No exchange of genetic material between homologous chromosomes
MEANWHILE:
Meiosis (only sex organs)
Involves _____ cells
Produces__(haploid/diploid)___ gametes
- SOMATIC (not germ cells)
- identical
- NO exchange
- Sister chromatids of each chromosome split - germ
- haploid
What happens during meiosis 1 and meiosis 2?
Meiosis I: chromosomes duplicate and exchange genetic material.
Results in haploid numbers of duplicated chromosomes
Meiosis II: No duplication of DNA
Daughter cells have haploid (1N) chromosomes… segregation of sex chromasomes provides mechanism of sexual dimorphism.
Females are arrested in prophase until when?
When is meiosis completed? Which phase is it stopped at 2nd?
How many daughter cells in spermatogenesis? Oogenesis?
- Primary oocyte arrested at birth
- until puberty - Upon fertilization with sperm –> stopped at METAPHASE II
- 4 daughter cells per germ cell in spermatogenesis, but oogenesis only makes one (plus polar bodies).
Meiosis in Male Gamete:
Spermatogenesis does not begin until ______.
Maturation usually requires how many days?
Normal sperm production requires ______
- puberty
- 60-70 days (continuous)
- Production may be 100-200 x 106 /day - reduced temp**
- testes outside the body
In females, loss of one X chromosome results in _______ but not loss of female ducts or genitalia.
ovarian dysgenesis
– still get female ducts & genitalia since the DEFAULT is the female pathway ( maleness is imposed by androgens)
-Ovary development depends on the presence of 2X and no Y chromosome
What does SRY encode?
Where is it found
SRY encodes TDF- testis determining factor
- found on Y chromosome
Define the following:
- Aneuploidy
- Mosaicism
- Chimerism
- Structural Errors
- Aneuploidy (Change in the number of chromosomes)
- Mosaicism (Different genotypes in different cells, arising from the same zygote)
- Chimerism (…arising from different zygotes that fuse during development).
- Structural Errors (e.g. unequal recombination, duplications, inversions)
Why is gonadal sex NOT hormone dependent?
What does it depend on instead?
this can’t be hormone-dependent, since the gonads produce the hormones.
- depends on GENE EXPRESSION
What happens when male hormones are absent? (no androgens?)
What happens in Turner’s syndrome? (XO)
progression to female structures occurs when male hormones are absent.
XO: turner’s syndrome: gonadal streak – indifferent = NO GONAD AT ALL!
State the what develops from the following in both males and females:
- Germ cell
- Coelomic Epithelium
- Mesenchymal Cells
- Germ cell = spermatogonia or oogonia
- Coelomic Epithelium: sertoli or granulosa
- Mesenchymal cells:
- LEYDIG & theca
What is the purpose of the following in males and females: (and which cells do they develop from)
- Sertoli or Granulosa cells
- Leydig & Theca Cells
- develop from Coelomic Epithelium:
- supporting cells that hold it & provide nutrition - Mesenchymal cells:
- hormone factory making testosterone or estrogen
Which cells make anti-mullerian hormone?
Which cells make androgens? (testosterone & DHT?
- Sertoli cells = antimullerian
2. Leydig = make testosterone & DHT
State the important points of the following:
- Primordial germ cells
- Primordial gonad
- Development of testis
- Primordial germ cells – migrate to gonadal ridge
- Primordial gonad – bipotential for testis or ovary (one way or the other)
- Germ cells direct the specific development of the gonad
- Development of testis – is not hormone dependent (medulla)
State the important points of the following:
- Development of medulla (XY)
- Development of ovary (cortex)
- Development of cortex (XX):
- Development of medulla (XY): Seminiferous tubules, Spermatogonia, Sertoli cells, Leydig cells
- Development of ovary (cortex) – is not hormone dependent
- Development of cortex (XX): Secondary sex cords, Oogonia, Theca cells, Granulosa cells
XY Medulla develops into what?
XX cortex develops into what?
Male = medulla
XY- medulla develops into 1) seminiferous tubules
2) spermatogonia
3) sertoli cells
4) leydig cells
XX- cortex develops into
1) secondary sex cords
2) oogonia
3) theca cells
4) granulosa cells.
Development of pubis hair requires what?
Developmental strategy – differentiation obeys _____ program if maleness is not imposed.
Sexual dimorphism is due to differences in the _____ of individual hormones and patterns of secretion.
ANDROGENS
feminine
- amounts
- There are no exclusive female or male hormones – both sexes have similar hormones and receptors.(AMOUNTS are important)
What is important for wolfing duct development?
What about degradation of malarian ducts?
What structure specifically determines the presence of mullein duct growth or wolfing ducts?
What happens when a female is treated with testosterone?
- testosterone
- Antimullerian hormone
- TESTES
- Antimullerian hormone causes degradation of mullerian ducts (produced by testes) WITHOUT TESTES = get mullerian ducts - Treat a female with testosterone - end up with BOTH
- _______become the epididymis, vas deferens, seminal vesicles, ejaculatory duct.
- _______develop and begin testosterone production, which promotes the development of #1
- Wolffian Ducts
2. Leydig cells
______ develop and begin producting antimullerian hormone (AMH), which causes MD atrophy.
Without AMH, what develops?
What happens if non-functioning androgen receptor?
- Sertoli cells
- AMH also coordinates development and stimulation of Leydig cells. (make more testosterone) - Without AMH
- development of fallopian tube, cervix, upper vagina
**Female structures develop without hormone but growth to normal size
requires ESTROGEN.
- XY genotype, but female phenotype
Female patterns of sexual differention occur in the absence of _____.
_____ directs testicular development before 9 weeks (gestation).
What cells produce testosterone?
What enzyme is needed to convert testosterone to DHT? What drug blocks this?
What is the function of DHT?
- testes
- TDF (testosterone deriving factor)
-After 9 weeks
without TDF an ovary develops. - Leydig cells –> testosterone –> increase androgen receptor –> internal male pattern development
- 5alpha - reductase
- Propecia (finesteride) - . DHT = male
genitalia development via androgen receptors.
What does DHT cause in males?
What drug can block the formation of DHT?
How?
DHT also causes male pattern baldness
- block with drugs = Propecia
prevent conversion of testosterone to DHT - male fetus will not have androgens = ambigous genitalia/ambigously female
drug Propecia
**BLOCKS 5 alpha reductase!!!
State the structures that develop from the following in females & males:
- Genital Tubercle
- Urogenital Folds
- Labioscrotal Folds
- Urogenital Sinus
- Female: clitoris
Male: glans penis - Female: labia minora
Male: ventral penis - Female: labia majora
Male: scrotum - Female: lower vagina
Male: prostate
- what is Gonadal dysgenesis?
- What is Seminiferous tubule dysgenesis?
- What is male pseudohermaphordism commonly due to?
- Congenital adrenal hyperplasia due to ______ deficiency
- (XO and variants)
- Klinefelter’s (XXY) and variants
- Androgen resistance (receptors)
- 21 hydroxylase
** needed for cortisol/aldosterone)
State whether gonad develops, mullein duct, or wolfing duct & the external genitalia in the following:
- XO Turner’s syndrom
- XY loss of X linked gene for androgen receptor
- XY deficient 5a-reductase
- XXY - Klinefelter’s syndrome
1. XO Turner's syndrome Gonad: STREAK** Mullerian: developed Wollfian: regressed External:FEMALE
2. XY loss of X linked gene for androgen receptor Gonad:testis Mullerian: regressed Wollfian: regressed** External: FEMALE
3. XY deficient 5a-reductase Gonad: testis Mullerian: none Wollfian: developed External: BOTH
4. XXY - Klinefelter's syndrome Gonad: dysgenic testis Mullerian: gone Wollfian: present External: MALE
What is the result when one X chromosome is not functioning in females?
TURNER’s
In females, the 2nd x chromosome is inactivated in all extragonadal tissues, but BOTH x chromosomes are needed in germ cells of the indifferent gonad in order to develop into oogonia.
no ovary = no estradiol
- normal uterus and cervix
If testes and some or all of the female tract and external genitalia are present, called _______.
If ovaries and some or all of the male tract and external genitalia are present, called _____
If both gonadal sexes are present, called ______
Hermaphrodites are typically ______(mosaic, chimeric, etc)
- MALE PSEUDOHERMAPHRODITISM.
- FEMALE PSEUDOHERMAPHRODITISM.
- HERMAPHRODITISM
- MOSAIC
The following describes what condition:
- Previously called testicular feminization.
- No pubic or axillary hair, undescended testes.
- Female habitus, genetic male.
**Example of male pseudohermaphroditism.
Androgen Resistance
The following describes what condition:
- XXY- Infertile, no spermatogenesis or seminiferous tubules.
- Decreased upper/lower segment ratio (eunuchoid), short arms.
- LOW TESTOSTERONE leads to gynecomastia, flat-topped (triangular) escutcheon.
- Most common form of primary testicular failure.
Klinefelter’s syndrome
- LACK OF TESTOSTERONE gynecomastia start producing estradiol
- escutcheon triangular pubic hair pattern
The following describes what condition:
- Developmental disorder- aplasia of the olfactory lobes, source of GnRH neurons.
- Anosmia and microphallus.
- Congenital GnRH deficiency primarily is a disease of males, with the male-to-female ratio being approximately 5:1.
Kallman Syndrome
no LH or FSH
underdeveloped genitalia
- do not migrate through the cribriform plate into the BRAIN
The following describes what:
- Virilization by androgens-
- advanced skeletal “age”,
- clitoromegaly and other ambiguities of genital anatomy.
FEMALE PSEUDOHERMAPHRODISM
- ovaries, but external genitalia looks masculine
What does the following describe:
Both gonadal sexes present, often as an “ovotestis”
TRUE HERMAPHRODISM
XX hermaphrodites generally raised as females, fertility has been reported in such patients.
Differentiation of external genitalia is highly variable
Cryptorchidism and hypospadias are common.
male seminiferous tubules and ovarian follicles
What is the action of inhibin?
What cells secrete it?
____ inhibits the secretion of LH by inhibiting the release of GnRh from the anterior pituitary
Inhibits secretion of FSH from anterior pituitary
Sertoli cells
- Testosterone
What synthesizes androgens?
What makes all circulating DHEA?
Peripheral tissues:
1. Adipose, brain, muscle, skin, adrenal cortex
- ADRENAL CORTEX
- less than 1% of all testosterone is from DHEA
- Adrenal androgens don’t influence male accessory organs
What converts testosterone to estradiol?
What converts testosterone to DHT?
LH controls the rate limiting reaction of converting what to what?
What cells make LH in the male?
AROMATASE, 5alpha - reductase
- Cholesterol to pregnenolone
- Leydig cells
- make testosterone
What are the five 19 carbon products?
- DHEA
- Androstenediol
- Androsterone
- Testosterone
- Di-hydrotestosterone
Plasma testosterone:
the following percentages express testosterone bound to what/free:
- 45%
- 55%
- 2%
- 45% = SHBG (sex hormone bindign globulin)
- 55% bound to albumin and CBG
- 2% free
- biologically active and may diffuse into cells
(does not need to bind to receptor on surface–> can bind in the nucleus)
ntracellular Testosterone:
- Binds to high affinity _____ receptor
- Or is converted to _____, then binds receptor
- Androgen receptor is what type of receptor?
- DHT – controlled by ____ enzyme
- androgen
- DHT
- NUCLEAR
Androgen–AR complex is a transcription factor that induces specific protein synthesis
- 5a-reductase
**
DHT is 30-50 fold more potent than “T”
Less than 2% of testosterone is ______
Remainder is converted to _____ and ____
which are conjugated to water soluble forms and excreted
- FREE
2. 17- ketosteroids & DHT
What is responsible for fetal development of the following: (testosterone or DHT)
Fetal:
- Epididymus
- Vas deferens
- Seminal vesicles
TESTOSTERONE
What is responsible for fetal development of the following: (testosterone or DHT)
Fetal:
- Penis, penile urethra
- Scortum
- Prostate
DHT
What is responsible for pubertal development of the following: (testosterone or DHT)
- Penis
- Seminal vesicle
- Musculature
- Voice
- Skeleton
- SPermatogenesis
TESTOSTERONE
What is responsible for PUBERTAL development of the following: (testosterone or DHT)
- scrotum
- prostate
- male pattern hair distribution
- beard, balding
- diamond shaped escutcheon instead of triangle
- Sebaceous glands
DHT
What is the treatment of Bening Prostatic Hypertrophy?
for Growth of prostate cancer ?
2
- 5 alpha -reductase inhibitor like finasteride (propecia)
- NO DHT = no prostate - is at least partly androgen dependent (DHT, and to a lesser extent testosterone)
TREATEMENT:
a) androgen receptor blocker
FLUTAMIDE
b) continuous long term GnRH agonist
You diagnose a male patient hypergonadotrophic hypogonadism. Which one of the following pathologies
could explain the high FSH/LH with low testosterone
Klinfelter’s syndrome
What are the direct actions of testosterone?
- epididymus, vas deferenes, seminal vesicles
- RBC
- Muscle
- Abdominal fat
- Liver (VLDL, HDL, LDL)
- low HDL, high other 2
What are the direct acts of DHT?
- Male pattern baldness
- Penis, scrotum, urethra, prostate (fetal)
- Prostate
- BEARD GROWTH
- Scrotum formation
What are the actions of both DHT and Testosterone?
DHT, Testosterone and Estradiol?
- Pubertal development of seminal vesicles
2nd:
- sperm
- feedback suppression of GnRH
- Imprint male pattern of gonadotropins, sex drive, behavior
