Sex determination Male vs Female: a continuum normal vs typical

1
Sex determinationMale vs Female a
continuumnormal vs typical
2
How is sex determined?

• Heat of passion
• Chromosomal-genetic
• Mammals
• Environmental

3
Genetic, chromosomal basis for sex determination
autosomes
Sex chromosomes
4
Chromosome-based sex determination in humans

• XX female
• XY male
• X0 female, sterile
• XXY male
• XYY male

A Y chromosome correlates with male
differentiation
5
Molecular mechanismwhats on the Y or X?

• Testis determining gene
• Female the default pathway
• Ovary determining gene

6
Two components to sex-specific differentiation

• Gonad differentiation and plumbing-during
  embryogenesis
• Secondary sexual characteristics-at puberty

7

• At 6 weeks
• an indifferent
• gonad with
• precursors for
• male and female
• ducts

8
male
female
9
Associated plumbing
10
Early stages of sex determination internal
Indifferent
Girl
Boy
11
(No Transcript)
12
(No Transcript)
13
External
14
What about the presence of a Y chromosome promotes
testis differentiation?
Sry gene ! Encodes a transcription
factor-turns on other genes
It promotes testis differentiation With
testis comes cells making two key
factors -testosterone-promotes Wolfian survival
and differentiation -MIS (mullerian inhibiting
substance)
15
Testis makes TestosteronegtWolffian duct
survival MISgtdestruction of Mullerian duct
Without these Two, no Wolffian, Mullerian
instead
16
Sry specifies testis differentiation
17
Sry transgenic XX mouse develops testis
18
(No Transcript)
19
Dax 1 looks like ovary- determining gene
20
Intersex
21
Hermaphrodite Pseudohermaphrodite
Intersex-Disorders of Sex Differentiation
(DSD) 1/1500-1/2000 births based on atypical
genitalia

• Combination of both male and female organs

• Gonad differentiation-secondary sexual
  characteristics disagree with sex chromosomes

22
Intersex people are
hermaphroditic. The word "hermaphrodite" has been
used to mean intersex in the past, but
biologically these are two different things. A
hermaphrodite is literally both male and female
that is, like snails and earthworms, these
organisms have both male and female reproductive
capabilities. There are no humans who are
hermaphroditic in this sense intersex in humans
refers to bodies that are not clearly
differentiated or consistent. Examples of
intersexuality in humans include a genetic male
born with external appearance of female
genitalia, or a genetic female born with an
enlarged clitoris that may appear like a
penis.Intersex people have sex chromosomes
other than XX or XY. Atypical sex chromosome can
influence the development of internal and
external reproductive organs, but account for
only a small percentage of intersex births. Most
people diagnosed with intersex conditions have
either XX or XY.Intersex people are neither
male nor female. This one depends on how rigidly
you define maleness and femaleness, but most
people born with intersex conditions do view
themselves as belonging to one binary sex or
another. They simply see themselves as a man (or
a woman) with a birth condition like any
other.Intersex people suffer from incorrect sex
assignment. This is true for some people, and for
these people it is a very important issue, but
not for the majority of people born with intersex
conditions. Intersex activists have criticized
cosmetic genital surgeries on unconsenting
children because of the physical, emotional and
sexual hazards that may result, and not
necessarily because a large number of intersex
adults feel that they were assigned the "wrong"
gender.Biologically speaking, there are five
sexes. This myth comes from Anne
Fausto-Sterling's infamous article, "The Five
Sexes" from 1993, but even she was merely
discussing the five-sex system as a
"tongue-in-cheek." Since human sex is on a
continuum, how many sexes there are depends on
where one draws the lines--and in that sense,
dividing humans into two categories is no
different from using five categories. That said,
to say that there are five sexes biologically
would require a radical re-formulation of what
"sex" means in Biology as a discipline, and
therefore it is premature, if not wrong.LGBT
groups should add the character "I" to include
intersex. While many organizations have taken
this path, intersex groups are not pushing for
this change. There are both benefits and risks to
associating intersex with LGBT that must be
evaluated case-by-case. LGBT groups can and
should act as allies to the intersex movement, as
they are also allies to women's movement and
other progressive causes, without hastily
changing their acronyms or mission statements.
Common misperceptions about intersex
23

• Androgen insensitivity syndrome
• XY, Sry present
• testosterone normal, receptor mutant
• Wolfian cant develop
• Is MIS, Mullerian degenerates
• Androgengt estrogen (estradiol)
• gtfemale traits
• Sterile

24
Steroid Hormone Biosynthesis, from testosterone
to estradiol
Focus here
25
Androgen deficiency-DHT deficiency

• XY
• Testosterone levels fine
• missing 5-alpha reductase enzyme so no DHT
• Comes in range of outcomes depending on whether
  low or no DHT
• Testis and male plumbing, underdeveloped penis,
  prostate
• At puberty with high testosterone, overcome DHT
  deficiency, testis descend-penis enlarges
• Sterile without surgery

26
5-??reductase deficiency- no DHT
Focus here
27
(No Transcript)
28
DHT deficiency
29
(No Transcript)
30
Congenital adrenal hyperplasia-no hydrocortisone
and make testosterone instead
XX masculinzed- No 21-hydroxylase, no
glucocorticoids, make more right side pathway,
increased Testosterone and DHT
X
31
Isna.com
32
Cross section through seminiferous tubule