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
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
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
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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
6 -4
© Biophoto Associates/Photo Researchers
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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 -5
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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.
6 -6
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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
6 -7
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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
6 -8
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
3 Classes of Genes on the Y
Genes shared with X
chromosome define the
pseudoautosomal regions
(PAR)
•Genes similar to X
chromosome genes are XY homologs
•Genes unique to the Y
including SRY gene
6 -9
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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
6 -10
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Y chromosome is highly repetitive
6 -11
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 10 -20 known genes including the
RSP gene for making ribosomes
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
6 -13
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
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?
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
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
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
SRY activates a cascade of
developmental events
6 -18
Sexual development
External genitalia differentiation
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Mutations in genes involved in sexual
development affect gender
Mutation/absence of:
SRY gene
Normal female development
Anti-Mullerian hormone
gene
Testosterone gene
Mullerian ducts persist in male
DHT converting enzyme
External structures lack signal
and develop as female,
internal structures are male.
6-21
Early development as female
Masculinization at puberty
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
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
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
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
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
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
3 WAYS TO MANIFEST TESTICULAR FEMINIZATION
XY (TDF del)
no testosterone
XY point mutation of TDF gene
no testosterone
XY with normal Y but with AIS mutation so
no receptors for testosterone
All these individuals will be tall
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)
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
SRY activates a cascade of
developmental events
6 -30
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
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
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Nondisjunction in Sex Chromosomes
X Chromosome
XXX
XXY
Klinefelter syndrome
XO
Turner Syndrome
6 -33
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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.
6 -34
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
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
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
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
XYY MALES
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