Week 4 Flashcards
(30 cards)
What did Aristotle believe about sex determination?
The heat of the male partner during intercourse determines the sex of the baby.
If the male’s heat overwhelms the womans coldness then a male will form.
What is sex determination?
The development of characteristics which allow an individual to be identified as male or female
Reproductive system
- Testis or ovary
External phenotype
Behaviour
- Hormone induced
Metabolism
What do sex chromosomes determine?
Sex
In mammals, the Y chromosome determines sex
Females XX
Males XY
Since females are XX, all oocytes carry an X chromosome
Males are XY so sperm can carry an X or a Y chromosome
So the sperm content determines the sex of the embryo
What is the bi-potential embryonic gonad?
Formation of ovaries or testes is an active gene directed process (no default state)
Early embryonic gonad is bi-potential
Sex differentiation at week 7 of development
Two systems of ducts
- Wolffian - male
- Mullerian - female
Development of male ducts is hormone dependent
Female duct phenotype (Mullerian) is the default
- Predominates in the absence of foetal testis
- Remove bi-potential gonads, female reproductive system develops
How do we make a male?
The Y chromosome determines male sex
140kb Sex determining region on Y chromosome
SRY gene
- Y-linked gene
SRY gene encodes transcription factors that activate testis formation
What do we know about SRY and mouse experiments?
SRY encodes testis-determining factor
Mouse experiments
- 140kb region of DNA including SRY gene
- Microinjected into pronuclei of fertilised XX mouse embryos
- Mice born as XXY
—> Developed testis, accessory organs and penis
Several testis-specific genes contain SRY-binding sites in their promoters
Binding of SRY to these sites initiated testis development
SRY is a testis determining factor
What are some other genes influencing male development?
Testis determining factor protein
- Encoded by SRY gene
- Testicular development
–> Leydig and Sertoli cell production
- Activates SOX-9 gene
SOX-9
- Sertoli cells
–> Induces steroidogenic factor 1 (SF1)
–> Upregulates anti-Mullerian hormone (AMH)
- Leydig cells
–> Induces steroidogenic factor 1 (Sf1)
–> Increase testosterone production
XX humans with an extra copy of SOX9 gene develop as males despite SRY absence
What causes development of the male?
In humans, SRY and SOX-9 genes stimulate the bi-potential gonad to form a testis
The testis produces 2 hormones
Testosterone
- Forms external male penis from urethral folds
- Wolffian duct becomes internal male reproductive system (epididymis, vas deferens)
Anti-mullerian hormone (AMH)
- Degeneration of mullerian duct
How do we make a female?
Females do not have a Y chromosome (SRY gene)
Is there an ovary-determining factor?
DAX1 gene
Identified in XY females
- Normal Y chromosome
- Duplication in the DAX1 region of the X chromosome
Disrupts SRY function
- Dysfunctional ‘testis’
Downregulates ‘testis’ Sf1 expression
- ‘Testis’ can’t produce testosterone
- Mullerian ducts predominate
Wnt4 gene
- Expressed in bi-potential gonad
- Undetectable in the XY gonad
- Maintained in the XX gonad
- XX Wnt4 knockout mice have abnormal ovaries
How does the female develop?
DAX1 and WNT4 stimulate bi-potential gonad to form an ovary
Ovary produced oestrogen
Oestrogen acts on Mullerian duct
- Development of uterus, oviducts and cervix
Is it only sperm chromosomes that influence sex of offspring?
No
Environment has a strong influence in some species
How does environment determine the sex of snapping turtles?
Below 22 degrees or about 28 degrees - FEMALES
Intermediate temperatures - MALES
How does environment determine the sex of American alligators?
Above 30 degrees - Female
Below 25 degrees - Male
At 28.5 degrees - Equal numbers of both
What do we know about temperature dependent sex determination?
Genotypic sex determination occurs in reptiles
Also, a thermosensitive period of development
Australian Skink
- Males XY
- Females XX
- Low temp: genotypic XX females become phenotypic males (XX males)
Australian Dragon Lizards
- Males ZZ
- Females ZW
- High temp; genotypic ZZ males become phenotypic females (ZZ females)
High temperature increases aromatase
- Converts androgens to oestrogens
- Biased sex ratio towards females
Parents can maximise their reproductive fitness by biasing birth sex ratio in favour of the gender with the greatest potential to outperform its peers!
What are the advantages of a skewed sex ratio?
Sex allocation hypothesis:
Dominant males father most offspring
Subordinate males do not mate
All females will get pregnant
- But, only females with high rank/body condition will produce males which join the dominant reproducing males
- Males born to nutritionally restricted mothers are smaller as adults than males born to mothers with good body condition
So, to maximise reproductive output:
Females with good condition should opt to produce male offspring
Females with poor condition should opt to produce female offspring
Supported in many wild species including deer and mice
What do we know about manipulation of sex ratio bias?
Adaptive control of gender bias
- Known to occur in many non-mammalian species
- Occurs as a response to changing environmental condition
–> Food availability, temperature, disease, population density, maternal condition, season
Fig wasp
- Low population density
- Sex bias in favour of males
–> Disperse to fertilise females in other colonies
–> Maximise genetic potential
–> Minimise inbreeding
Ruff
- Poor food availability
- Sex bias in favour of females
–> Maximise offspring production
–> Don’t waste food on multiple males
You only need 1
–> Cost to the mothers
How do red deer determine sex?
Maternal dominance correlates to offspring sex ratio
Dominant females have more male offspring
- Dominance correlates with testosterone concentration
This sex bias is eliminated with high population density
- Nutritional stress
- Increased confrontation to maintain dominant position
- All males will have the chance to mate?
How do American Opossum determine Sex?
Maternal condition correlates offspring sex ratio
Increase in male offspring with high n-3 fatty acid diet
- Marsupials move to the pouch 14 days after conception
Mechanisms must act before conception or on very early embryo
How do non-human primates determine sex?
Maternal condition correlates offspring sex ratio
Social structure is important
- Colobine monkey high ranking females have more males
- Opposite is true in baboons (matriarchal society)
Can humans control offspring sex?
Humans show adaptive control of gender bias
- Socioeconomic variables (famine)
- Environmental stressors
- Psychological stress
Pre-conception nutrition
- Maternal diet high in omega-6 polyunsaturated fatty acids (vegetable oils)
–> Increased females born
Recent evidence, not a consistent dietary intake that determines offspring sex, but a change in nutritional status
- Females gaining condition produce sons
- Females losing condition produce daughters
What are some environmental stressors in humans?
Exposure of males to endocrine disruptors skews sex ratio in offspring
Dioxin exposure of males at puberty
- Bi-product of chemical, steel/iron industry
- increased male offspring in adulthood
Dichlorethylsulfide (mustard gas)
-Exposure of iranian soldiers in iran-iraq war
- Decreased male:female ratio in offspring
- Decreased testosterone:gonadotrophin ratio in males
Increased sperm DNA damage
–> Sperm DNA integrity linked to the ability to progress through the female tract
–> Are Y chromosome sperm more susceptible to chemically induced DNA damage?
What are some environmental stressors in humans?
Severe life event pre-conception or early pregnancy
Death/cancer diagnosis of spouse or child
Decrease in male:female sex ratio
- Differential fertilisation - more X chromosome sperm fertilised?
- Differential embryo survival - more XY embryos aborted?
Kobe earthquake and 10 day war in slovenia
Both resulted in decrease in male:female sex ratio
Reduced sperm motility
- Stress induced increase in prolactin and testosterone in males
- Interfere in spermatogenesis
- Differential effect on X or Y bearing spermatozoa?
Confounding factors with psychological stress!
- Sexual abstinence
- Hormone concentrations differ from the norm
- Poor nutrition
- All affect semen quality and embryo survival
How might mothers influence the sex of their children (pre and post-conception)?
As the female has a disproportionate role in production of offspring it is likely that most influence on offspring sex ratio is under maternal control
Female reproductive tract might control gender bias
- Sex specific sperm selection/progression?
- Sex specific fertilisation?
- Sex specific embryo implantation/survival?
Less ‘costly’ for female to manipulate gender bias before/at fertilisation than later during pregnancy
How is the female reproductive tract selective?
Female tract is not passive - it controls sperm progression
- Pig, 30 billion sperm inseminated, but only 1000-5000 reach oviduct
- Human, conception falls 40% to 24% <1.5million sperm inseminated
Cervix: mucus removes DNA damaged sperm
- Possibly because DNA-damage is reflected in poor motility
Uterus: immunological (neutrophils) removal of membrane damaged sperm
Utero tubal junction
- Prevents 90% of sperm in uterus passing into oviduct
- Restricts entry to minimise polyspermy
- Opportunity to exercise choice
Oviductal storage/selection
Controls which sperm are given access to the oocyte
