lecture 23: diseases and disorders 1: non-human sex differentation Flashcards
1
Q
What is vertebrate phylogeny?
A
- hormonal influence
- gold fish
- frog
- snakes
- birds
- genetic influence
- platypus → XY chromosome arise
- kangaroo
- mouse
- human
- common ancestory drosophila
2
Q
What are different animal models of sexual differentiation?
A
- mouse model (Genetic sex determination, XY/XX)
- marsupial model (GSD, XY/XX)
- avian model (GSD, ZW/ZZ)
- reptile model (environmental sex determination)
- fish sex differentiation (GSD/ESD)
- drosophila (GSD, XY/XX)
- nematode sex differentiation (XO/XX)
3
Q
What are sexual differentiation events?
A
- days from fertilisation
- E9.5 germ cell migration to gonads
- E10.5 indifferent gonads, onset of testicular differentiation
- E10.5 to 12.5 sex determination window
- E13.5 onset of ovarian differentiation
- E13.5 entry into meiosis
4
Q
How do testes develop in the mouse?
A
- testis cord in testes
- adjacent to mesonephros
- germ cells are surrounded by sertoli cells, PM cells to form testis cords
- leydig cells reside outside testis cords
5
Q
What is gonad development in the mouse embryo?
A
- Sf1, Wt1, Lhx9, M33, Emx2 → at this stage gonad has potential to form testis or ovaries
- E10.0-11.5 - indifferent gonad
- SRY → SOX9 (Fgf9 [important for proliferation of somatic cells and differentiation of sertoli cells], AMH [important for regression of the mullerian duct], Dmrt1 [related to double sex in drosophila, promotes and maintains testis development]) → E12.5 XY gonad
- wnt 4 Fst → E12.5 XX gonad → E18.5 XX gonad
6
Q
What is the model of sex development in the tammar wallaby (marsupial)?
A
- postnatal development → short gestation, long lactation
- before birth there is no difference between testis and ovary
- male:
- onset of testicular differentiation v soon after birth (before 1 day)
- testicular cords visible from day 2
- female
- onset of ovarian differentiation 6.5 days after birth
- cortex and medulla visible ~8 days
- slower
7
Q
What determines sex differentiation in the marsupial?
A
- GSD XX:XY (SRY)
- marsupial key sex determining and differentiation genes
- SRY, Sf1, Fgf9 → Sox 9 → male specific targets
- master regulator → Wnt4 (beta catenin → female specific targets), FoxI2 (aromatase → E2-ER, inhibits Sox9, female specific targets, self promotion)
8
Q
What is eostrogen sex reversal?
A
- testes become ovary when treated with oestrogen
- formation of cortex and medulla
9
Q
What was seen when doing RT-PCR of the cells in the E2-treated testes?
A
- SRY and AMH are greatly downregulated when treated with E2
- however SOX9 levels had no change
- where is SOX9 located
10
Q
What is the sox9 protein distribution in sex reversed testes?
A
- cytoplasmic
- usually in sertoli cell nucleus
11
Q
What is the effect of oestrogen treatment on the female pathway?
A
- genes are greatly upregulated
12
Q
So what is the effect of oestrogen on the sex differentiation pathway?
A
- inhibits SRY
- inhibits nulcear sox9
- inhibits AMH
- therefore inhibits testis
- upregulates female pathway leading to development of ovary e.g. Wnt4, FoxL2
13
Q
What is sex determination in the chicken?
A
- genetic sex determination
- ZZ (male): ZW (female)
- testis
- seminiferous cords
- reduced cortex
- arrested germ cells
- ovary
- fragmented medulla
- thickened cortex
- meiotic germ cells
14
Q
What is gona development in the chicken?
A
- at 4.5 days the gonads are undifferentiated
- morphological differentiation incubation day 6.5
- lots of genes are expressed in these processes
- SF1
- two genes important for the male pathway: Dmrt1, SOX9
- different chromosomes, conserved genes
15
Q
How is sex determined in most reptiles?
A
- environmental
- temperature sex determination in reptiles
- for macroclemys temminckii → betewen 24.5 and 27 degrees C, more than 50% are male, higher than that majority female
- for trachemys scripta, below 28, 100% male
- alligator has a similar curve but at different temperatures
- with climate change, if temperature increases 2 degrees, huge impact on ratio of males to females
16
Q
What is environmental sex determination (ESD)?
A
- occurs in most turtles and all crocodilians
- incubation temperature of eggs in critical time window → sex
- small change can have huge effect on sex ratios
- primarily controlled by modifying oestrogen production
- male temp → inhibits aromatase gene → testicular development
- female temp → aromatase gene → oestrogen → ovarian development
18
Q
What is fish sex reversal?
A
- many fish are serial hermaphrodites
- juvenile → male → female
- juvenile → female → male
- which pathway is better in terms of reproductive strategy?
- female to male
- sex changed
- colouration
- behaviour
- gonadal sex
- nemo?
- clown fish
- dominant female and nondominant male and undifferentiated
- remove dominant female and the male becomes female
19
Q
What is medaka fish sex differentiation?
A
- GSD XX XY (DMY)
- DMY → foetal testis → Dmrt1 → adult testis
20
Q
How is sex determined in drosophila?
A
- the ratio of X chromosomes : autosomes determines sex
- (A)X:A ration = 1.0 = female
- = 0.5 = male
22
Q
How is sex determined in C. elegans?
A
- XX hermaphrodite: both ovary and testes
- XO male: testis only
- the primary sex determination depends on the ratio of X chromosome to autosomes same as drosophila
23
Q
What is the mechanism of sex determination in C. elegans?
A
- master sex switch gene: xol-1
- on in X:A = 0.5
- off in X:A = 1.0
- DM domain transcription factor:
- mab3: on if xol-1
- male
