Sex Determination Flashcards
Olympics and Women History
1896 – First modern Olympic games
1900 – First women’s events (22 women)
Individuals = Tennis + Golf
Team = Sailing + Croquet + Equestrianism
1928 – Short running events added
1936 – Alpine Skiing + Gymnastics
1991 – Any new sport must have a men’s and women’s division
Caster Semenya Scenerio (What happened to her)
She is an elite female athelete competing at the international level
She was raised a gril and indeitifies as a women and hasn’t considered any other possibilities
One of her competators questions whether she was truly biologically female and anaonymoiusly asks offcials to investighate her sex
The group that makes the rules about who can complete is decdinng whetehr you qualify as female and should be able to compete
Who decides who can compete/in what catagory
- International Association of Athetics Federations (IAAF) – now called World Athetics
- International Olympic commitee (IOC)
***Policies made by these givering bodies are tyopically used as models for other organizations – their rules are modeled by other agencies = these agencies make the guidence
When does the development of sex begin
Development of sexes begin around 7 weeks in Utereo
Male Development of Sex in Utero
The autosomal gene SDRD5A2 codes for an exnymes involoved in porcesses testostrone into DHT –> required for male sex charachteristic develment
- Mutations to SDRD5A2 = unable to processes teststrone = leads to incomplete male development
What is required for male development in Utero
The autosomal gene SDRD5A2 codes for an exnymes involoved in porcesses testostrone into DHT – required for male development
Sex Development in Utero
Sex is indistiguishable until 7 weeks
Have some cells that turn into a penis or a vagina
Have Indifferent gonads cells – can turn into testes or ovaries (you can;t know what they will turn into until 7 weeks)
Have Indiferent gential cells – turn into penis or vagina
Indiferent genitals Vs. indifefrent gonads
Indiferent genitals = Develope into penis or vagine
- Same cells that can direct one way or other
Indifferent Gonads = develope into ovaries or testes
Sex development is…
complex
Genes involoved in sex development
Involoves sex linked and autosmal genes
Have genes on X that can activate cascade of events from genes that are on autsoomes –> creates cascade that leads to make or female development
- Genes on X that activate cascade of genes on Autosomes
- There are many pathways that form
Three catagories of sex
- Male
- Female
- Intersex
Intersex
Umbrella term to describe individulas with sex charachteristics (gentials + gonads + Chromsome patterns) that do not fit the typical defintion for male or female bodies
Any deviation from standrd path
Example – Indifferent gential cells go one way and indiffrent gonads go a different way
What can intersex include (what can be affected)
- Number and types of sex chromsomes
- Gonads (overies and testes)
- Sex hormone levels
- Internal reproductive anatomy (ex. Uterus)
- External Genetelia
Gonads
Overies + Testes
Sex hormones
Testrone + Estrogen
Bimodal vs. Binary sex
Sex is Bimodal NOT binary
Have male + female BUT have things in between
- Most people fit into male and demale BUT intersex is not male or female
- How do you define male/fenake
We try and fit somthing into a binary (try and fit sex into a binary) that is not actually a binary (sex is not a binary)
Two main chatagories of intersex varaitions
- Sex chromsomes anuploidy
- DNA variations that affect sexual development
Sex chromsome anuplidies
- Turner Syndrome (XO)
- Klinfelter syndrome (XXY)
- XYY Syndrome (XYY)
- Triple X Syndrome (XXX)
- Moaicism (XX/X, XY/X, XX/XXY)
ALL can lead to intersex
DNA varaitions that affect sexial development
Can also lead to intersex
- Andrigen Insensitivity syndrome
- Congential Adrenal Hyperplasia (CAH)
- Other genetic varaitions
Andrigen Insensitivity syndrome
Low response to hromones (low response to testrone)
- Body doesn’t repsond to hormones
- Recptors for hormones don’t work
Common cause of XY females (Develope as a female)
Congential Adrenal Hyperplasia (CAH)
High production of homrones (high production of testrone)
XX indiviuals with CAH can be:
1. Typical male
2. Combines male and female charachteristics
3. Tyoicaly female
Have a lot of varaition in how individuals develope
XY females
Have SRY gene that activates male cahacteristics BUT that genes doesn’t function –> If gene doesn’t function (like if you have a mutation on Y) = won’t develope as a male
These women all develope as women even though XY
SRY gene
SRY gene = gene on Y that activates male charchteristics
XX males
Occurs because have X and Y chromsomes that don’t normally recombine BUT sometimes they do –> if have recombination that puts the SRY gene on the X chromsome and that recombind X chrosmome with SRy gene goes to gamete then have XX that has SRY gene = have male developmnet
Autosomal mutations
There are other autosmal mutations that can redirect paths –> can produce lots of testastone
Thing in her ldies – check to see if added around slide 11
How common is intersex
Intersex variation as a group are quite common – 1.7% of population
Why do we not see intersex as often (intersex invisabikity)
- People choose not to share personal information – people tend not to talk about it
- Many intersex people don’t know they are intersex
Why don’t many intersex people know they are intersex
- No outward signs = don’t even know
- Might be so minor it is not observed
- Surgery preformed during infancey or early childhood
- Used to be surgery is the sex wasn’t sure
Genetic tests + Intersex
Genetic tests may reveal unexpected infomration about sex chrosmomes
THIS IS SOO COMMON – so comon that they have a landing page for it – common enough to have a page for it
- “If you are here it may be because your geentic sex from DNA analysis is difefrent than you self-reproted sex. There are many reasons this can happen…”
Sex and Gender
NOT the same thing
A person’s gender may be difefrent than the sex typically assigned at birth
Sex
Classifcation of people in male + female + Intersex
Based on physical characteristics including:
1. Chrosmomes
2. Sex hromones
3. Reproduyctive organs
Has genetic compoennt
Gender
A person’s sense of veing a man or women or both or beother
May or may not have a strong genetic compoennet –> Don’t know if genes play a role in gender (defintley not a single gene – complcated system)
Based on societal ideas of masculinity and femininity
History of olympic sex testing
1936 – IOC preforms strip searches
1965 – IOC begins chromosomal analysis (Karyotype)
1967 – IOC and IAAF begin Barr Body testing
1992 – IAAF ends chromosome testing
1996 – PCR tests to look for the presnece or absence of teh Y-linked SRY gene
- DNA test to look at the presnece/absence of SRY
1999 – 8 of 3387 females tested positive for SRY gene –> ALL 8 were subject to further testing (Andrigen testing) and all 8 were eventually allowed to compete
AFTER = they stoped sex testing
2000 – teststrone levels used to determine eligibility to combete in women’s events – 10 ng/L limit
What can Barr body testing distiguish
Barr body testing can destiguish XX from XY BUT not XX from XXY
XX and XXY = both have 1 Barr body
Ewa Klobukowska
Polish olypic sporinter with genetic mosaicism with soem cells that are XX and some that are XXY –> she became the first athele to fail the gender verification tests due to her “extra chrosome”
- She was stripped of her medals and world records
- Some cells have XX Karyotype and some of XXY karyotpe
AFTER THIS = decided to just look at Barr Bodies
Genetic Mosaiscm ex.
Some cells = XX and some XXY
- Some cells have XX Karyotype and some of XXY karyotpe
Maria Jose Martinez Patino
Spanish hurdler – was disquilified after sex verification showed she had XY chrosmomes
- She protested the disqualification based on having Andrgen insensitivity syndrome and was eventually reinstated
- NOW – she is professor and write a lot about the sydnrome and sex testing in sprots
She had XY – had androgen insensitivity syndrome
What sex does SRY gene indicate
Indivates presence of Y chromosome
Caster Semenya and Dutee Chand
cater = disqulified from compinatition due to naturally elevated teststrine in 2009
- She begaan taking medicine to lower her testsrine levels
Dutee Chad = disquilified due to naturally elevated testrone level –> BUT she didn;t want to take drugs to lower level
- She fought back –> What is so special about 10 ng/L
They both tested high testrine levels – could take drugs to lower levels to compete
Options for female athletes who test high testrone levels
IF tested high testrine levels – could take drugs to lower levels to compete
Endocrine profiles in 693 elite atheles in post competition setting study
They looked at the hormone levels of elite atheltes right after competiton
The IAAF used this data to make an upper limit of testrone level that still allows women to compete
END = They concluded 10 nm/L –> Was at the lwo end of the male testrone range
What does this figure show
X axis = testrone level
Y axis = Number of althetes
Blue = female
Green = male
Shows the number of atheles in that particular testrone level
Shows where most women are and where most men are BUT note there are some women in the men range and some men in the women range
Advice for intersex athletes – if they are not qualified to compete based on testrone levels
recommend surgery so you appear more female – told them to get a gonadetcomey
Propose – partial clitordectomy with bilatoral gonadectomy follwoed by a deffered femanizing vaginioplasting and estrogen replrcemnt theraopy
***4 female althese had surgery
Health risks of Gonadectomy
Requires liftime hormone replacment + get Stereloity + compromise bone and muscle strength + leave people at risk for chronic weakness + depression + sleeo disrtubance + poor libedo + Adverse effects on lipid profiles + diabetes + faturgue + finicial bruden + exlusion from reproductive technologues
Legal challenges to 10 ng/L rule
2014 – Chand brought legal challegnges gaainst IAAF
2015 – court suspended 10 nm/L limut and ordered IAAF to provide scientific evidence of testrone imporving perfermence
BIG question after testrine limit was placed
How do we know that testrone level improves preferance
IAAF follow up strudy (After tesing hormone levels in altheste)
Looking to see how we know that testrone level imporves preformance
TWO questions to be answered:
1. Do naturally occuring elevated testrine levels confer an athletic advantage?
- If there is an advantage – what what level of testsrone does that advantage become unfair?
Study = compared prefermane of females woth lowest level and highest levels of testrone
Results: Of 21 events – high levels of testrone show statistically significnat imoporvement in preformance in 5 events
What events are there would you put regulations on?
Which events showed significance for higehr testrone levels?
400 m
400 m hurdles
800 m
Pole valut
Hammer throw
THESE = have * –> means there is significant difference between low and higehst 1/3 of testrone levels
Results of Does testrone imporve prefermance
Of 21 events – high levels of testrone show statistically significnat imoporvement in preformance in 5 events
Lowest fT tertike vs. Highest fT tertile
Lowest = lowest 1/3 of testrone levels
Highest = highets 1/3 of testrone levels
Which of the events showed that testrone porvided an advantage
400 m Hurdles and non-hrudles
Which of the follwoing non-running events showed that testrone provided an advatage
Hammer throw and pole vault
Result of IAAF study – things that they applied the testrone limit to
HERE - they put a limit to testrone level because statistics showed adavantage
400 m hurdles
400 m
800m
1500m (had no significnat advtange)
1 Mile (not even in the study)
ALSO – they lowered the threshold to 5nm/L
Controversy over the new rule
- Marginal Advatage to those with increased testrone
- New rule does not apply to the events with the strongest correlated between incerased testosterone and imroved perfermence (Doesn’t include hammer throw and pole vault)
- New limit applies to 1500m races even though the stidy did not show imporved performance correlated to eleveated testosterone and included 1 mile even though it was not studies
- 5 nm/L is aritrary
Critism on IAAF study (Testrone advatge study)
- Some atheles included were doping – researchers knowingly incldued data from atheete disqualofied for doping
- Use of bad data –> some duplicated data + some fabicated/erreneous data – Looked like there was some duplicated data
Current regulations
5 nm/L limit for XY females for 400m/400m hurdles/800m/1500m/mile
Affect of current regulations on Chand and Semenya
Chand = can complete – regulations don’t apply to 100m events
Semenya = runs 800m = has options
1. Lower testrone via medication or surgey
2. Participaye in event not in regulation (She did this)
3. Enter only non-international competitions (not covered by rules)
4. Compete in men’s division
5. Possible compete in another third division that doesn’t exist yet
Options for XY women who exceed limit
- Lower testrone via medication or surgey
- Participaye in event not in regulation (She did this)
- Enter only non-international competitions (not covered by rules)
- Compete in men’s division
- Possible compete in another third division that doesn’t exist yet
State laws for school sports
2020 – fairness in women’s sports act (Idaho)
2021 – Other states introduced similar bills (Tenessee + Alabama + Montana + Florida)
2022 – IOC requesting new guidelines
Consider the results from physical, genetic, and hormonal sex determination tests
for a female athlete:
Physical characteristics: female genitals fully formed
Genetic test findings: no Barr body present, no SRY gene present
Hormone test findings: Testosterone (T) = 1.2 nmol/L
What is the most likely karyotype of this individual? Keep in mind that a genetic mutation to a particular gene is unlikely to alter the chromosome structure
XY
Consider the results from physical, genetic, and hormonal sex determination tests
for a female athlete:
Physical characteristics: female genitals fully formed
Genetic test findings: Barr body present in some cells and absent in others, SRY
gene present
Hormone test findings: Testosterone (T) = 3 nmol/L
What is the most likely karyotype of this individual? Keep in mind that a genetic mutation to a particular gene is unlikely to alter the chromosome structure
XXY/XY mosaic
Consider the results from physical, genetic, and hormonal sex determination tests for a female athlete:
Physical: characteristics: genitals neither typically male nor typically female
Genetic test findings: Barr body present, SRY gene absent
Hormone test findings: Testosterone (T) = 6.3 nmol/L
What is the most likely karyotype of this individual? Keep in mind that a genetic mutation to a particular gene is unlikely to alter the chromosome structure.
XX
Consider the results from physical, genetic, and hormonal sex determination tests for a female athlete:
Physical characteristics: female genitals fully formed
Genetic test findings: Barr body absent, SRY gene present
Hormone test findings: Testosterone (T) = 25 nmol/L
What is the most likely karyotype of this individual? Keep in mind that a genetic mutation to a particular gene is unlikely to alter the chromosome structure.
XY
Consider the results from physical, genetic, and hormonal sex determination tests for a female athlete:
Physical characteristics: genitals neither typically male nor typically female
Genetic test findings: Barr body absent, SRY gene present
Hormone test findings: Testosterone (T) = 12 nmol/L
What is the most likely karyotype of this individual? Keep in mind that a genetic mutation to a particular gene is unlikely to alter the chromosome structure.
XY
