Transcript Sexual Development/Differentiation

Sexual
Development &
Differentiation
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Sex & Gender
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Sex and Gender
 Sex
 genetic
sex - chromosomes
 anatomical sex - internal and
external genitalia
 sexual identity - one’s identity as
male or female
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Sex and Gender

Gender
 social meaning attached to being male
or female
 gender identity - sense of being male or
female
 gender role - expectations about how a
male or female should behave
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SCIENTIFIC BASIS OF FERTILITY
OVARIAN
DIFFERENTIATION
SEX DIFFERENTIATION
TESTIS
SPERMATOGENESIS
AND SPERM TRANSPORT
FOLLICULAR GROWTH
AND OVULATION
SPERM - OOCYTE
FUSION
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Gender identity is the end result of genetic hormonal
and morphologic sex as influenced by the environment
Genetic sex (chromosome )
¯
Gonadal sexual (testis, ovaries)
¯
Hormones affecting sex development of fetus
+
External genitalia
Hormone production at Puberty
CNS
Sex assignment and rearing
Gender identity
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Normal Prenatal Development:
Genetics

Chromosomes
 each human cell contains 46 chromosomes,
occurring in pairs
 23 pairs of chromosomes
 22 autosomes (determines e.g., hair color)
 23rd pair are the sex chromosomes
 male: XY
 female: XX
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Normal Prenatal Development:
Genetics….
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Normal Prenatal Development:
Genetics….

Germ cells:
 male: sperm - contains “X” or “Y”
 female: ovum - contains an “X”
 “Y” chromosome contains less genetic
material than “X” chromosome
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Normal Prenatal Development:
Genetics….
Mother
XX
Father
XY
X
X
X
Y
XX
XY
XX
XY
female
male
female
male
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Normal genital development
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The mammalian fetus has an inherent tendency to
develop into a female.
The primitive human gonad starts to develop
between the 4th and 6th week of fetal life deriving
from cells of endodermal origin that migrate from
the yolk sac to the genital ridge.
The gonad is initially bipotential and develops into
a testis or ovary depending upon karyotype.
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Normal Sex Differentiation
Intermediate Mesoderm
WT/SF1
XY/XXY Bipotential gonads XX/XO
SRY SOX9
Wnt4
DAX1- Antitestis
Testis
Sertoli cell
Ovary
Granulosa
Cell
Leydig cell
Theca
Cell
No AMH
No T
5-R
AMH
No mullerian
Duct
No uterus
T
DHT
Follicles
Wolffian
Mullerian
Duct
Duct
Male internal
genitalia
Male External
Genitalia
Oestrogen
Progesterone
Female
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Internal Genitalia
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Male genital development
Y-Chromosome
Testicular differentiation
Leydig cells
Sertoli cells
Testosterone
Anti-Mullerian hormone
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6th weeks gestations, still in bipotensial gonad.
Fetus has genital duct premordial (Mullerian
duct and Wolfian duct) and axternal genitalia
premordial .
8th-12th gestation, placental gonadotropin
increase: stimulate Leydig cell for testoteron
producing and sertoli cell for Mullerian inhibiting
factor (MIF) producing .
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Normal Prenatal Development:
Internal & External Genitalia

Sexual differentiation: Gonadal development
 8 weeks gestation
 Y chromosome synthesis of H-Y antigen
 Male: H-Y antigen causes undifferentiated
sex glands to develop into testes
 Female: lack of H-Y antigen causes
undifferentiated sex glands to develop into
ovaries
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Normal Prenatal Development:
Internal & External Genitalia

Sexual differentiation: Duct development

both sexes start out with two systems:
 Mullerian ducts - will develop into fallopian
tubes, uterus, inner vagina
 Wolffian ducts - will develop into
epididymis, vas deferens, and seminal
vesicles
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Testosterone
dihydrotestosterone
Anti-mullerian hormone
Virilization of external genitalia
Inhibition of mullerian ducts
Wolfian ducts
Male internal genitalia
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Male sexual differentiation is initiated by the
SRY gene on the short arm of the Y
chromosome.
Under the influence of SRY, the undifferentiated
gonad forms a testis: testosterone stimulates
the wolffian structures (epididymis, vas
deferens, and seminal vesicles), and antiMullerian hormone suppresses the development
of the Mullerian structures (fallopian tubes,
uterus, and upper vagina).
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Male genital development
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Presence of Y chromosome
Testicular hormone production
Normal responsiveness of androgendependent tissues
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The conversion of testosterone to
dihydrotestosterone occurs in the skin of
the external genitalia and masculinizes
the external genital structures.
 Most of this male differentiation takes
place by about 12 weeks, after which the
penis grows and the testes descend into
the scrotum.
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CAH 46 XX
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Infants whose genitalia are obviously
ambiguous are investigated at birth so that
sex of rearing can be assigned.
In many cases, however, appearances are
deceptive:
An infant with what appears to be bilateral
cryptorchidism might be assumed to be a
boy because of a normal-appearing phallic
structure but in fact may be a girl with
severe virilizing congenital adrenal
hyperplasia (CAH).
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An apparent female infant with only slight
clitoral hypertrophy may be a genetic male
with severe androgen insensitivity,
necessitating eventual removal of the
testicles to avoid malignant degeneration.
It is necessary, therefore, to have welldefined clinical criteria for the investigation
of intersexuality
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Female genital development
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Spontaneous process independent of hormonal
influences.
Without Y chromosome the primitive gonads
develop into ovaries.
Mullerian ducts develop into female internal
genitalia
Lower end of vagina forms from the urogenital
sinus
External genitalia similarly develop
spontaneously.
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Normal Prenatal Development:
Internal & External Genitalia

Undifferentiated stage:
 0-7 weeks gestation
 male and female external genitals the same
 urogenital fold
 genital groove
 genital tubercle
 labioscrotal swelling
 male and female internal genitalia the same undifferentiated sex glands
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Normal Prenatal Development:
External Genitalia
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External Genitalia
Normal Prenatal Development:
Internal Genitalia
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Male (XY)
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Testes secrete testosterone and Mullerianinhibiting hormone
testosterone - Wolffian ducts begin to develop
Mullerian-inhibiting hormone - inhibits further
development of Mullerian ducts - they shrink and
degenerate
Female (XX)

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absense of Mullerian-inhibiting hormone Mullerian ducts develop
absense of testosterone - Wolffian ducts
degenerate
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Normal Prenatal Development:
Internal & External Genitalia

Sexual differentiation: Genital development
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Male (XY): testosterone causes unisex genitalia to
develop into penis and scrotum
 testosterone converted to dihydrotestosterone
 dihydrotestosterone causes the external
appearance of scrotum and penis
Female (XX): absence of testosterone causes
unisex genitalia to develop into clitoris, labia,
vaginal opening, etc.
NOTE: The default is the develop as a female. Male hormones
are needed to promote differentiation into a male
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Normal Prenatal Development:
The Brain

Sexual differentiation:
 Male:
 Testosterone secreted → blood → brain
 testosterone converted to estradiol and DHT in the
brain
 estradiol masculinizes the brain
 Female:
 alpha-fetoprotein binds to estradiol
 prevents estradiol from entering the brain
 protects female brains from being masculinized by
estradiol
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Hypospadias
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