1. Sex for the purposes of this class refers to 4 components
Gonadal sex
Gonads or where gametes are produced by meiosis
Somatic sex
Somatic cells are cells that undergo mitosis.
They can be divided into primary and secondary characteristics
Secondary somatic sex characteristics are divided further into hair and body
Sexual identification
Sexual orientation

2. FOR HUMAN MALES Gonadal sex
Consists of the testes where the gametes or sperm are produced
Somatic sex characteristics
Primary and Secondary
Male primary somatic sex characteristics
penis and scrotum
Male secondary somatic sex characteristics
Hair
facial hair chest hair body hair
Body
pelvic build straight hips
muscular build upper body
Ability to generate muscle mass at a faster rate than females following puberty

3. FOR HUMAN FEMALES Gonadal sex Ovaries where eggs are produced
Female primary somatic sex characteristics
Clitoris, labia, vagina, cervix, uterus, fallopian tubes, and the ability to bear children
Female secondary somatic sex characteristics
Hair vellus rather than terminal hair
Body
rounded hips, breasts, ability to nurse offspring, menstrual cycle, increased body fat composition, decreased upper body strength, decreased ability to generate muscle mass at a fast rate

4. © Biophoto Associates/Photo Researchers
Sex chromosomes
At the cellular level the
sex of an individual is
determined genetically
by the sex chromosomes.
X and Y -> male
X and X -> female
© Biophoto Associates/Photo Researchers

5. Sex chromosomes determine gender
Human males are the heterogametic sex with two different sex chromosomes, (XY).
Human females are the homogametic sex (XX).
In other species sex determination differs:
male birds ZZ
female birds ZW

6. Sexual development At the beginning of human
development either male or
female development is
possible.
Unspecialized gonads and
two sets of reproductive
ducts exist until 6th week of development.
An embryo develops as a
male or female using
information from the Y
chromosome.

7. Genes on the Y chromosome
Y chromosome first seen 1923
Tips of Y chromosome are pseudoautosomal regions PAR1 and PAR2
They make up 5% of the chromosome
Contain 63 pseudoautosomal genes that cross over with the X chromosome
Most of the Y is male specific region or MSY

8. Genes on the Y Chromosome
Y chromosome has 2 pseudoautosomal regions whose genes match genes on the X chromosome
And a large central region that does not recombine with the X chromosome
This non-recombining region makes up about 95% of the chromosome

9. 3 Classes of Genes on the Y
Genes shared with X chromosome define the pseudoautosomal regions (PAR)
Genes similar to X chromosome genes are X-Y homologs
Genes unique to the Y including SRY gene

10. Genes on the Y chromosome
Y chromosome is small and gene poor and prone to deletion
Since the Y can not recombine with X, its genes began to rot
Genes decayed except for SRY and the tips
The Y is degrading fast, losing genes at the rate of 5/million years
May have a way out of complete degredation
Many of the DNA segments are palindromes

11. Y chromosome is highly repetitive

12. During male meiosis a synaptonemal complex forms and one chiasma will always form in this region
This results in regular exchange of material between the tips of XP and YP
Any genes in this region are inherited as thought they are autosomal and that is why it is called the pseudoautosomal region PAR
Contains known genes including the RSP gene for making ribosomes

14. SEX REVERSAL
This mutant hybrid chromosome is called an X (TDF) chromosome
When it fertilizes an X bearing egg it results in a 46 XX (TDF) male
When the corresponding mutant y chromosome fertilizes an egg it results in a 46 XY female

15. SEX REVERSAL
Karyotype is XX but this individual will develop as an XY male because of the presence of the testes determining factor gene
Remember the presence of testes, determines gonadal sex in males
Even though these individual will look male they will suffer from testicular atrophy or small testes and sterility
What causes the sterility?

16. SEX REVERSAL
In humans if there are 2 X chromosomes in a male germ line , it acts as a poison to the germ cells and kills them during meiosis
The gonadal sex of this individual will be male because they will have testes
But they can not make viable sperm

17. SEX REVERSAL
When a sperm carrying a Y (delTDF) chromosome fertilizes an X bearing egg the result is an
XY(delTDF) zygote
This individual develops as female even though the karyotype is XY
Ovaries are reduced and eggs that are produced will not survive
Have a female build but little pubic or underarm hair

18. SRY activates a cascade of developmental events

19. Sexual development

20. External genitalia differentiation

21. Mutations in genes involved in sexual development affect gender
Mutation/absence of:
SRY gene Normal female development
Anti-Mullerian hormone Mullerian ducts persist in male
gene
Testosterone gene Early development as female
Masculinization at puberty
DHT converting enzyme External structures lack signal
and develop as female,
internal structures are male.

22. HORMONES Travel in the blood stream to receptors on the target cell
Receptors bind the hormone and carry it across the plasma membrane of the cell to the nucleus
Once inside the nucleus the hormone binds to DNA to promote gene expression
It is the protein products of these genes that lead to sexual differentiation

23. HORMONES
Chemical messengers that are produced by one cell type, released into the bloodstream and received by the target cell
Hormones regulate gene expression in the target cell
We will look at:
testosterone
excreted by testes and adrenal cortex in males
estrogen
excreted by ovaries and adrenal cortex in females

24. HORMONE RECEPTORS AND GENE REGULATION
The TDF gene is on the Y chromosome and codes for the development of testes which produce testosterone
But the receptor for testosterone is regulated by a gene on the X chromosome
This AR gene or androgen receptor gene codes for the testosterone receptor
A mutation in this gene cause testicular feminization
Individuals are XY with a normal Y chromosome with a normal TDF gene

25. HORMONE RECEPTORS AND GENE REGULATION
They can not respond to testosterone’s masculinizing effects because they have no receptors to transport testosterone across the cell membrane
Affected individuals develop as phenotypic females who are sterile
This mutation is known as the AIS mutation, androgen insensitivity syndrome

26. ANDROGEN INSENSITIVITY SYNDROME
Produce testosterone
This is where they differ from the XY (TDF del) individuals
They have no receptors to transport testosterone across the cell membrane
Referred to as AIS females
Occur 1/20,000 births
Taller than average
External genitals are female
Vagina looks normal from the outside
Newborn is declared a girl and raised as such

27. ANDROGEN INSENSITIVITY SYNDROME
In utero AIS females develop testes because TDF gene present so their gonadal sex is male
Produce MIF and Mullerian ducts regress
But the cells of the embryo cannot sense testosterone
Instead they respond to the low levels of estrogen being produced by the adrenal cortex and develop as female
At birth appear female
No vagina, cervix, uterus or fallopian tube

28. 3 WAYS TO MANIFEST TESTICULAR FEMINIZATION
XY (TDF del)
no testosterone
XY point mutation of TDF gene
XY with normal Y but with AIS mutation so no receptors for testosterone
All these individuals will be tall

29. SEX DETERMINATION IN HUMANS REQUIRES 4 ELEMENTS TO BECOME MALE
Y chromosome intact TDF gene (no point mutations)
Sensing mechanism in the indifferent gonad to the testes determining factor
Testosterone or estrogen produced by the gonads
Testosterone or estrogen receptors in the somatic tissues intact. No AIS (androgen insensitivity syndrome)

30. SRY activates a cascade of developmental events

31. Born XY with female genitalia
GUEVEDOCES
Born XY with female genitalia
At puberty the adrenal gland begins to produce testosterone
Causes masculinization
voice deepens
muscles develop
no breast development and no menses
adrenal testosterone causes clitoris to enlarge and resemble a penis

32. SEX CHROMOSOME ANEUPLOIDY
Aneuploidy refers to an abnormal number of chromosomes
Such anomolies occur often enough that they have been recognized and studied by medical science
We will discuss 3 different cases of aneuploidy
Klinefelter males XXY
XYY
Turner syndrome XO

33. Nondisjunction in Sex Chromosomes
XXX
XXY
Klinefelter syndrome XO
Turner Syndrome

34. What determines gender?
Number of X chromosomes, or
presence of Y chromosome?
Individuals with unusual chromosome
combinations provide a clue: X0
XXY
XY females
XX males
Female with Turner syndrome
Male with Klinefelter syndrome
SRY gene missing
Small bit of Y with SRY gene present
=> Y chromosome determines gender.
=> SRY gene on Y chromosome determines gender.

35. KLINEFELTER
Klinefelter males have an extra X chromosome so they karyotype as XXY males
Occurs 1/1000 live births
1940 Harry Klinefelter at Massachusetts General Hospital described a syndrome occurring in males not usually detected until after puberty

36. The testes are atrophied and do not produce much testosterone
KLINEFELTER
The testes are atrophied and do not produce much testosterone
The level may be so low as to be about the same amount as the estrogen produced by the adrenal cortex
Because the level is so low during puberty these individuals do not undergo normal development of male secondary sex characteristics, including muscular upper body, narrow hips and chest and facial hair

37. Remain sterile because the undeveloped testes can not produce sperm
KLINEFELTER
If treated during puberty with testosterone then breast development will stop and the hips will narrow and become more male like
They will develop muscular upper bodies, broad shoulders, square jaw and deep voices
Remain sterile because the undeveloped testes can not produce sperm
But outwardly they will look like normal males

38. They found 7 of those males had a 47 XYY karyotype
XYY MALES
1965 Jacobs in Scotland looked at the chromosomes of 197 mentally subnormal males with violent tendencies
They found 7 of those males had a 47 XYY karyotype
7/197 = 1/28 a much higher ratio than among other groups of males tested
XYY occurs 1/1000 live births
Among tall males about 1/325
Among tall penal inmates 1/30

39. XYY males are over represented in mental and penal institutions
Large scale study done by the Danish government suggested that tall males with lower intellectual function are more likely to be convicted of crimes regardless of their karyotype
XYY karyotype is over represented in tall males 1/325
More than 95% of all XYY males are not in prison