Basics of Reproduction

Question 1

what is sexual differentiation?

Answer 1

formation of the male internal and external genitalia

Question 2

what is genotypic/embryological sex?

Answer 2

based on presence of XX or XY chromasome

Question 3

what is gonadal sex?

Answer 3

presence of ovaries or tester

Question 4

what is phenotypic sex?

Answer 4

based on internal and external genitalia

Question 5

what is legal sex?

Answer 5

the sex which is placed on birth certificate/ passport etc.

implicated in sports, marriage, hereditary - prince/princess

Question 6

what is gender identity?

Answer 6

gender based on how a person feels - their perceived gender

Question 7

how is gonadal sex determined?

Answer 7

XY chromosome causes SRY to be expressed on Y chromasome –> acts as a transcription factor –> causes formation of the testes NOT ovaries

Question 8

what is SRY?

Answer 8

Sex determining region Y

Question 9

at what point is SRY expressed?

Answer 9

week 7

Question 10

other than testicular development, what effect does SRY have?

Answer 10

Sertoli Cell production – forms AMH - mullarian duct regression

Leydig Cell production - produces testosterone - causes internal genitalia formation - epididymis, vas defferens, seminal vesicle and prostate

Question 11

at what point do the genital ridges change from bipotential to specific - why?

Answer 11

bipotential - mullarian and wolffian ducts present

week 7 - expression of SRY leads to sertoli cell formation – AMH causes regression of the malarian duct and the Wollfian duct remains patent.

Question 12

where does the genital ridge arise from?

Answer 12

primordial mesenchymal germ cells

Question 13

what is the role of primitive sex cords in the genital ridge?

Answer 13

run ontop of the genital ridge - migrate along
in the male - migrate in a long thin wave - become the Sertoli cells secreting AMH
in the female - migrate in bursts - form the granulosa/follicular cells - secrete oestrogen

Question 14

what is the role of 5 alpha reductase/

Answer 14

conversion of testosterone to DHT in the genital skin

DHT acts as a potent androgen causing differnetiatiion of the male external genitalia

Question 15

how does the male external genitalia develop?

Answer 15

genital tubercle develops into the glans penis
labia fuse and become rugged into the scrotum
prostate formation
urethral plate expands and rolls over to become the penile urethral fold

Question 16

how do the female external genitalia develop?

Answer 16

in the absence of DHT, the labia, vagina and clitoris remain patent

Question 17

what happens when testosterone is converted to oestrogen - what effect can this have?

Answer 17

oestrogen and other steroid hormones used in the development of the CNS - become the cortex, limbic system and spinal cord

excessive sex hormone can lead to people ‘feeling’ the wrong sex - there is a change in nuclear neuronal size

Question 18

what is gonadal dysgenisis - what is an example of this condition?

Answer 18

when sexual differentiation is incomplete - usually due to a lack of SRY in males, or only one X chromosome in females

Turners Syndrome

Question 19

what are the symptoms of Turners Syndrome?

Answer 19

there is a lack of testes due to no SRY
but there is ovarian dysgenisis due to only one X chromosome –> failure of function
there is a lack of DHT so uterus and tube form - they are small due to a defect in growth and development

Question 20

is it possible for people with turners syndrome to be fertile?

Answer 20

yes if they have a mosaic mutation for the disease

Question 21

what is sex reversal?

Answer 21

when the phenotype does not match the genotype

Question 22

what is intersex? what condition does this occur in

Answer 22

when there is components of both tracts - e.g. a uterus with testes

Androgen insensitivity syndrome

Question 23

what is AIS - what is the presentation?

Answer 23

XY individual
testosterone is produced but does not have an effect- e.g. receptor mutation, defect in second messengers

normal teste formation due to SRY
female external genitalia due to absence of testosterones action

Question 24

what are the two types of AIS?

Answer 24

complete = undescended testes, appear female at birth

partial = SOME modulation of the receptor - varying degrees of penile and scrotal development
- can start with female gentialia and then develop penis and testes at puberty

Question 25

what are the factors for diagnosis of AIS?

Answer 25

``` primary amennhorea lack of body hair undescended testes karyotype of male male levels of androgens ```

Question 26

how is AIS treated?

Answer 26

see what the patient decides based on their gender identity | surgery

Question 27

what is the effect of a 5 alpha reductase deficiency

Answer 27

testosterone is present but no DHT due to a mutation in the enzyme normal production of the testes using SRY differentiation and growth of the wolfing duct structures due to the presence of testosterone NO MALE EXTERNAL GENITALIA sudden increase in testosterone at puberty can cause virrilisation may feel male even if female

Question 28

what is the inheritance pattern for 5 alpha reductase deficiency?

Answer 28

autosomal recessive

Question 29

How does CAH occur? explain using the steroid pathway?

Answer 29

steroids formed from cholesterol cholesterol taken into cells and modified through the steroid pathway side chain cleavage enzymes forms a 21C progesterone skeleton progesterone converted to cortisol in the adrenal cortex by 21-hydroylase DEFICENCY OF 21-HYDROXASE IN CAH so there is a build up of progesterone excess progesterone shunted into androgen pathway forming testosterone very small amount of testosterone converted to oestrogen low levels of cortisol feeds to the hypothalamus causing CRH release CRH release causes ACTRH release from pituitary ACTH causes uptake of cholesterol into the adrenal cortex upregulates cholesterol levels to try to increase cortisol unsucsessful due to deficiency - leads to further increase in testosterone

Question 30

what effect does high levels of androgens due to CAH have?

Answer 30

coffin ducts do not regress - so seminal vesicles and vas deferens form mullarian ducts are present due to no AMH - so there is formation of the uterus, uterine tubes and upper 1/3rd vagina ovaries present DHT levels are high - so there is formation of male external genitalia lack of aldosterone means there is no water regulation - so causes salt wasting -- treat with glucocorticoids.

Question 31

what is behavioural sex?

Answer 31

the exposure or lack of exposure of the brain to testosterone during development - effects: = sexual beahviours = sexual orientation = increased aggression = increased rough and tumble play in the prepubertal stage

Question 32

what is the role of the HPG?

Answer 32

control of reproduction through MAINLY negative feedback

Question 33

what is the pathway which controls the release of oestrogen, progesterone and testosterone from the gonads?

Answer 33

kisspeptin --> activates hypothalamus --> GnRH release to anterior pituitary --> LH and FSH release from anterior pituitary --> gonads

Question 34

how does GnRH reach the anterior pituitary to produce an effect?

Answer 34

via the primary plexus - binds to gonadotroph cells the produce LH or FSH

Question 35

what is the difference between the structures of gonadal hormones?

Answer 35

common alpha subunit differing hormone specific beta subunit differing glycosilation patterns to match the specific receptors

Question 36

how is GnRH released in pulses? what is the relevance to this?

Answer 36

using a pulse generator to maintain frequency and amplitude slow pulse frequency causes FSH release fast pulse frequency causes LH release pulses vital for maintaining control of the menstrual cycle

Question 37

what is the time frame for GnRH release?

Answer 37

30-120 mins in females- depending on stage in the menstrual cycle 90-120 mins in male

Question 38

what type of hormone is GnRH?

Answer 38

small decapeptide- cleaved from a large preprohormone

Question 39

how are gonadotrophin hormones released?

Answer 39

pulsatile due to gnRH release - although not vital to function

Question 40

what is the role of LH?

Answer 40

stimulates leydig cells to produce testosterone stimulates theca cells to produce androgens stimulates ovulation and production of corpus luteum

Question 41

what is the role of FSH?

Answer 41

control of sertoli cells and spermatogenesis control of the follicle and granulosa cells - formation of oestrogen from the theca androgens

Question 42

what happens if there is defect in the LH receptor?

Answer 42

there is no ovulation | so the person is infertile

Question 43

what is the role of synthetic GnRH?

Answer 43

stimulation of the HPG

Question 44

what is the role of GnRH analogues?

Answer 44

inhibition of the HPG agonists - cause decoupling of GnRHr from the G-protine second messenger over a few weeks antagonists - bind to the GnRH receptor and stops binding

Question 45

when might GnRH analogues be used?

Answer 45

PCOS endometritis IVF - prevents FSH and LH release - can then be given exogenous forms to control menstrual cycle prostate and breast cancer which are hormone specific gondal protection before chemotherapy - stops the DNA from being damages