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Sex Determination and Development

of Reproductive Organs
Sex determination
The SRY+ gene is necessary and probably
sufficient for testis development
The earliest sexual difference appears in the gonad
Genital duct development
External genitalia development
Synthesis of mammalian sex hormones
Hormonal control of fetal sexual development
Hormonal control of postnatal sexual development

Sexual dimorphism

In many species, adult


males and females differ
not only in their
reproductive organs but
also in secondary sex
characteristics, such as
size, weaponry, and
ornaments. 
In deer, males are
considerably larger and
seasonally produce large
antlers, which they use
for fighting.

A male is an individual with testes.


A female is an individual with ovaries.
A true hermaphrodite is an individual
with both testicular and ovarian tissues.
Sex Determination is the natural
event by which an organism is set to
become either a male or a female.

Sex Determination in mammals


depends on Y Chromosome
In the presence of a Y chromosome, a male
develops.
In the absence of a Y chromosome, a female
develops.

Genotypic sex determination in mammals.


Males have two sexually dimorphic chromosomes, designated X and Y, while
females have two X chromosomes. A stands for one complete set of non-sex
chromosomes, or autosomes. Thus, males produce two types of sperm,
designated AX and AY. This system generates a sex ratio (proportion of male
offspring ) of 0.5, as long as XA and YA sperm fertilize equally well, and
provided that AAXX and AAXY embryos are equally viable.

Sex Determination and Development


of Reproductive Organs
Sex determination
The SRY+ gene is necessary and probably
sufficient for testis development
The earliest sexual difference appears in the gonad
Genital duct development
External genitalia development
Synthesis of mammalian sex hormones
Hormonal control of fetal sexual development
Hormonal control of postnatal sexual development

Sex Determination and Development


of Reproductive Organs
Sex determination
The SRY+ gene is necessary and probably
sufficient for testis development
The earliest sexual difference appears in the gonad
Genital duct development
External genitalia development
Synthesis of mammalian sex hormones
Hormonal control of fetal sexual development
Hormonal control of postnatal sexual development

Primary sex differentiation in the human embryo


All diagrams show
transverse
sections. (a)
Indifferent gonad
during 6th week of
gestation. (b)
Ovary during 7th
week. Cortical
(outer) portions of
primitive sex cords
form follicles. (c)
Testis during 8th
week. Medullary
(inner) portions of
primitive sex cords
form testis cords.

After the indifferent stage, the activity of Sry+, a Y-linked gene,


is critical: It controls the production, in the developing testis,
the differentiation of cells producing two key hormones:
testosterone and anti-Mllerian hormone

Seminiferous
tubules in
mammalian testis
(a) schematic drawing
of testis
(b) photograph showing
tubules in cross section
(c) drawing of segment
outlined in part (b)

Sex Determination and Development


of Reproductive Organs
Sex determination
The SRY+ gene is necessary and probably
sufficient for testis development
The earliest sexual difference appears in the gonad
Genital duct development
External genitalia development
Synthesis of mammalian sex hormones
Hormonal control of fetal sexual development
Hormonal control of postnatal sexual development

Indifferent stage of human sexual development


shown in transverse section. 
The immigrating primordial germ cells are surrounded by proliferating
gonadal epithelial cells to form primitive sex cords. The mesonephric
(Wolffian) and paramesonephric (Mllerian) ducts are both in place. The
former functions at this stage as part of the embryonic kidney.

Genital duct development in the human female


(a) Fourth month of gestation. Both Mllerian and Wolffian ducts are in place.
(b) At birth, the proximal portion of each Mllerian duct has formed an oviduct. The
distal portions of both Mllerian ducts have fused to form uterus and upper vagina. The
Wolffian duct has degenerated.

Genital duct development in the human male


(a) Fourth month
of gestation. The
proximal portion of
the Wolffian duct is
embedded in the
embryonic kidney.
(b) After descent
of the testis, the
mesonephric
tubules have
become efferent
tubules. The
Wolffian duct has
formed epididymis,
ductus deferens,
and seminal
vesicle. The
Mllerian duct has
almost completely
degenerated.

Sex Determination and Development


of Reproductive Organs
Sex determination
The SRY+ gene is necessary and probably
sufficient for testis development
The earliest sexual difference appears in the gonad
Genital duct development
External genitalia development
Synthesis of mammalian sex hormones
Hormonal control of fetal sexual development
Hormonal control of postnatal sexual development

Development of the
external genitalia in
the human
The genital tubercle forms
either the corpora cavernosa of
the penis or all of the clitoris.
The urogenital groove becomes
either the urethra or the
vestibule of the vagina.
The urethral folds form either
the corpus spongiosum of the
penis or the labia minora.
The genital swellings give rise
to either the scrotum or the
labia majora.

Sex Determination and Development


of Reproductive Organs
Sex determination
The SRY+ gene is necessary and probably
sufficient for testis development
The earliest sexual difference appears in the gonad
Genital duct development
External genitalia development
Synthesis of mammalian sex hormones
Hormonal control of fetal sexual development
Hormonal control of postnatal sexual development

Synthetic pathways
for vertebrate sex
steroid hormones 
Testosterone is synthesized via
progesterone from cholesterol.
In the presence of the enzyme
aromatase, testosterone is
converted into estrogen.
In the presence of 5reductase, testosterone is
converted to 5dihydrotestosterone.

Gene Activation by Steroid Hormones


Steroid hormones (including
progesterone and
testosterone) have receptor
proteins. The hormone binds
to the receptor while
displacing an inhibitory
protein. Two hormonereceptor complexes typically
form a dimer that binds to
specific DNA sequences
(steroid response elements).
In concert with other
transcription factors, the
bound dimer controls the
transcription of several
target genes.

Sex Determination and Development


of Reproductive Organs
Sex determination
The SRY+ gene is necessary and probably
sufficient for testis development
The earliest sexual difference appears in the gonad
Genital duct development
External genitalia development
Synthesis of mammalian sex hormones
Hormonal control of fetal sexual development
Hormonal control of postnatal sexual development

Somatic sexual development in mammals. 


Primary (gonadal) sex differentiation depends on the Sry+ gene, whereas
secondary sex differentiation is controlled by sex hormones produced in the
gonads.

Genetic Disorders Interfering with


Secondary Sex Differentiation
Congenital adrenal hyperplasia (CAH)
based on loss-of-function alleles for enzymes converting
progesterone to metabolic steroids. Leads to elevated
testosterone and masculinisation in females.

Androgen insensitivity loss of function in Xlinked gene for androgen receptor. Allows development of
female external genitalia and secondary sex characteristics
in males with normal SRY+ and (non-descended) testes.

Guevedoces (penis at 12 years of age) - based


on autosomal recessive alleles for 5--reductase, which
metabolizes testosterone to DHT. Affects only males.

Sex Determination and Development


of Reproductive Organs
Sex determination
The SRY+ gene is necessary and probably
sufficient for testis development
The earliest sexual difference appears in the gonad
Genital duct development
External genitalia development
Synthesis of mammalian sex hormones
Hormonal control of fetal sexual development
Hormonal control of postnatal sexual development

How Male and Female Brains


Become Different

Sex differences in brain development and activity


Distribution of sex hormone receptors in the brain
Seasonal hormone levels control bird singing
Perinatal exposure to sex hormones affects adult
reproductive behavior and brain anatomy
The organizational hypothesis
Congenital adrenal hyperplasia
Progestin-induced pseudohermaphroditism
Gender has biological underpinnings

How Male and Female Brains


Become Different

Sex differences in brain development and activity


Distribution of sex hormone receptors in the brain
Seasonal hormone levels control bird singing
Perinatal exposure to sex hormones affects adult
reproductive behavior and brain anatomy
The organizational hypothesis
Congenital adrenal hyperplasia
Progestin-induced pseudohermaphroditism
Gender has biological underpinnings

Sex hormone receptors


have distinct distributions
in the brain.
Photographs show frontal sections of
lizard brains hybridized in situ with
probes for mRNAs encoding specific
hormone receptors. 
Androgen receptor mRNA (top)
accumulates in brain areas involved in
aggression and copulation, such as
AME and NSL.
Progesterone receptor mRNA
(bottom) accumulates in areas
involved in ovulation and sexual
receptivity. 
Other brain areas (including MPA)
show mRNAs for both receptors.

Hormones Cause Sex-Specific Brain Activity

The receptors for androgens (AR), estrogen (ER), and progesterone (PR) have
distinct distributions , which are alike in men and women. Nevertheless, the
prevalence of different hormones leads to sex-specific brain activity patterns.

How Male and Female Brains


Become Different
Sex differences in brain development and activity

Distribution of sex hormone receptors in the brain


Seasonal hormone levels control bird singing
Perinatal exposure to sex hormones affects adult
reproductive behavior and brain anatomy
The organizational hypothesis
Congenital adrenal hyperplasia
Progestin-induced pseudohermaphroditism
Gender has biological underpinnings

How Male and Female Brains


Become Different

Sex differences in brain development and activity


Distribution of sex hormone receptors in the brain
Seasonal hormone levels control bird singing
Perinatal exposure to sex hormones affects adult
reproductive behavior and brain anatomy
The organizational hypothesis
Congenital adrenal hyperplasia
Progestin-induced pseudohermaphroditism
Gender has biological underpinnings

Sexually dimorphic nucleus of the preoptic area


(SDN-POA) in the rat hypothalamus
The SDN-POA is located on both sides of the third ventricle (V) of the rat
brain and is larger in normal males (a) than in normal females (b). 
Perinatal treatment of rats with either testosterone (c) or its estrogen
metabolite (d) enlarges (masculinizes) the SDN-POA.

(a)

(b)

(c)

(d)

Third interstitial nucleus of the anterior hypothalamus (INAH3) in the human

How Male and Female Brains


Become Different

Sex differences in brain development and activity


Distribution of sex hormone receptors in the brain
Seasonal hormone levels control bird singing
Perinatal exposure to sex hormones affects adult
reproductive behavior and brain anatomy
The organizational hypothesis
Congenital adrenal hyperplasia
Progestin-induced pseudohermaphroditism
Gender has biological underpinnings

How Male and Female Brains


Become Different

Sex differences in brain development and activity


Distribution of sex hormone receptors in the brain
Seasonal hormone levels control bird singing
Perinatal exposure to sex hormones affects adult
reproductive behavior and brain anatomy
The organizational hypothesis
Congenital adrenal hyperplasia
Progestin-induced pseudohermaphroditism
Gender has biological underpinnings

Congenital Adrenal Hyperplasia or


Progestin-Induced
Pseudohermaphroditism
Female infants with
this genetic or
maternal medicationinduced disorder
show enlargement of
the clitoris and fused
urogenital folds.

How Male and Female Brains


Become Different

Sex differences in brain development and activity


Distribution of sex hormone receptors in the brain
Seasonal hormone levels control bird singing
Perinatal exposure to sex hormones affects adult
reproductive behavior and brain anatomy
The organizational hypothesis
Congenital adrenal hyperplasia
Progestin-induced pseudohermaphroditism
Gender has biological underpinnings

From E.O. Wilson (1975)

Five male archers advance in single file, led by a man in a head


dress. They seem confident, almost cocky. Archers are typically
found in cave paintings of Cro-Magnons dating 12-4 kya.

Cro-Magnon woman strolling


with a child whose hair is
pulled up in twin puffs.
The hand-holding and the
womans attentive posture
suggest the child is her
daughter, and that children
were raised primarily by their
mothers.

How Male and Female Brains


Become Different

Sex differences in brain development and activity


Distribution of sex hormone receptors in the brain
Seasonal hormone levels control bird singing
Prenatal exposure to sex hormones affects adult
reproductive behavior and brain anatomy
The organizational hypothesis
Congenital adrenal hyperplasia
Progestin-induced pseudohermaphroditism
Gender has biological underpinnings