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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 Sex and Gender
• Androgyny/hermaphrodism
– sex: possessing both male and female
reproductive organs
– gender: possessing both male and female
qualities

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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 Father
XX XY

X X X Y

XX XY XX XY
female male female male

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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:
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
– Male (XY)
• Testes secrete testosterone and Mullerian-inhibiting hormone
• testosterone - Wolffian ducts begin to develop
• Mullerian-inhibiting hormone - inhibits further development of Mullerian
ducts - they shrink and degenerate
– Female (XX)
• 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
– 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:
External Genitalia

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Normal Prenatal Development:
Internal Genitalia

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 Normal Prenatal Development:
The Brain
• Sexual differentiation:
– Male:
• Testosterone secreted into the blood reaches the brain
• testosterone converted to estradiol and dihydrotestosterone 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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 Normal Prenatal Development:
The Brain
• Prenatal hormone exposure fundamentally organizes
the brain:
– Sexual/Reproductive Behaviors:
• development of the hypothalamus (sexual orientation)
– Problem Solving
– Aggression
– Rough-and-tumble play
• Hormone exposure seems to involve a critical period -
exposure outside the critical period does not have the
same impact on brain organization

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 Brain Development:
Sex Differences
Given different selection or evolutionary
pressures on men and women, how would
you expect men and women to differ with
regard to intellectual skills? In other words,
in which areas would men demonstrate
superior skill (on average), and in which
areas would women demonstrate superior
skill (on average).

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 Brain Development:
Sex Differences
• Men:
– spatial rotation tasks
– mathematical reasoning tasks
– navigation through a route
– guiding or intercepting projectiles
• Women:
– perceptual speed - rapidly identifying matching items
– mathematical calculation tasks
– greater verbal fluency
– recalling landmarks from a route
– faster at precision manual tasks

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 Brain Development:
Sex Differences
• How meaningful are these sex differences?
• What is the effect size?
• Does a large effect size indicate that you are
unlikely to find a woman who is better than
a man at spatial rotation? A man that is
more verbally fluent than a women?

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 Brain Development:
Sex Differences

Do sex differences in skills arise from

evolutionary pressures or cultural
pressures? In other words, are the data
consistent with an evolutionary
interpretation or a cultural interpretation?
Both? Neither?

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 Brain Development:
Sex Differences
• Animal studies:
– Observational studies regarding spatial learning
indicate:
• female rats use landmarks (pictures), male rats use geometric
cues (angles)
• in the absence of landmarks, female rats use geometric cues
• male rats almost exclusively used geometric cues

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 Brain Development:
Sex Differences
• Lutchmaya et al. (2002)
– Obtained amniotic fluid from 87 pregnancies
– analyzed for fetal testosterone
– 40 girls, 47 boys followed up at 18 and 24 months after birth
– Findings:
• girls had significantly larger vocabulary
• fetal testosterone inversely correlated with vocabulary size when
both sexes examined together
• fetal testosterone not correlated with vocabulary size when sexes
examined separately

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 Brain Development:
Sex Differences
• Shute et al. (1983)
– 91 male and female students
– administered spatial test battery
– measured androgen levels
– Findings:
• curvilinear relationship between androgen levels and spatial
abilities
• high androgen females better spatial abilities than low androgen
females
• low androgen males better spatial abilities than high androgen
males

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 Brain Development:
Sex Differences
• Gouchie & Kimura (1991)
– 46 females, 42 males, 18-31yrs
– measured spatial ability, math ability, perceptual speed,
verbal articulation, and vocabulary
– measured salivary testosterone
– Finding:
• men with lower T performed better on spatial and math tasks
than higher T males
• women with high T performed better than low T females

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 Brain Development:
Sex Differences

Consider these findings from an evolutionary

perspective. What might be the adaptive
benefit of having high or low testosterone for
males and females?

What do these findings suggest about

androgyny?
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 Brain Development:
Sex Differences
Menstrual cycle fluctuations
• Hampson (1990)
– 45 19-39yr old females
– tested cognitive skills across the menstrual cycle
– Findings:
• Estrogen levels high:
– lower performance on spatial skills, abstract reasoning
– higher performance on verbal articulation, fine motor skills
• Estrogen levels low:
– better performance on spatial skills, abstract reasoning tasks
• Note: Effect sizes small

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 Brain Development:
Sex Differences
Seasonal fluctuations
• Kimura & Hampson (1994)
– men experience seasonal fluctuations in
androgens such that T is lowest in the spring
– seasonal fluctuations in androgens correlated
with performance on cognitive tasks
– T levels lower in the spring -> spatial ability
improved in the spring

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 Brain Development:
Sex Differences

What might be the evolutionary

significance of these findings? Why might
it be beneficial for men to have better
spatial skills in the spring?

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 Brain Development:
Sex Differences
Hemisphere Differentiation
• right hemisphere involved in spatial
functions
• left hemisphere involved in language

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 Brain Development:
Sex Differences
Hemisphere Differentiation
– de Lacoste-Utamsing & Holloway (1982)
• examined brains of 12 humans at autopsy
• Findings:
– female brains had larger corpus callosum

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 Brain Development:
Sex Differences
Hemisphere Differentiation
• Davatzikos & Resnick (1998)
– MRI study of 114 patients, aged 56-85yrs
– Finding:
• women have larger corpus callosum
• size of corpus callosum positively correlated with
cognitive skills in women, but not men

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 Brain Development:
Sex Differences
Hemisphere Differentiation
• de Lacoste et al. (1991)
– examined 21 fetal brains in utero
– Findings:
• males showed greater asymmetry than females
• right hemisphere thicker in males than females

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 Brain Development:
Sex Differences
• McFadden (1998)
– Sex differences in auditory system
• females:
– greater hearing sensitivity
– greater susceptibility to noise exposure at high freq.
– More spontaneous otoacoustic emissions
• Males:
– better sound localization
– detecting binaural beats
– detecting signals in complex masking taks

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 Brain Development:
Sex Differences
• McFadden (1998)
– Sex differences in auditory system
• female differences less evident at first half of menstrual cycle
• female differences less evident among female from oppisite-sex
female twin pairs

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Abnormal Development

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 Abnormal Development
Intrauterine exposure to abnormal hormone levels:
• Animal studies: Spatial learning tasks
– Observational studies indicate:
• female rats use landmarks (pictures), male rats use geometric cues
(angles)
• in the absence of landmarks, female rats use geometric cues
• male rats almost exclusively used geometric cues
– Experimental studies indicate:
• depriving newborn male rats of testosterone, and administering
estrogen to newborn female rats -> produces reversal of these sex
typed behaviors

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 Abnormal Development
Intrauterine exposure to abnormal hormone levels:
• Resnick et al. (1993)
– 422 twin pairs, of which 51 opposite-sex pairs, 15-70 yrs
– completed Sensation-Seeking Scale
– Speculated that intrauterine testosterone would affect females in
opposite sex pairs
– Finding:
• female opposite sex twin pairs more disinhibited, experience seeking,
greater overall sensation seeking
• male opposite sex twins did not differ from male same sex twins

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 Abnormal Development
Congenital Adrenal Hyperplasia (CAH)
• genetic defect leading to excessive production of androgens
• girls exposed to excessive androgens prenatally
• (taking synthetic steriods prenatally can produce similar condition to CAH)
• Results:
– masculinization of the genitals (which can be surgically corrected)
– masculinization of the brain (based on interviews with subject, mother,
teachers):
• more tomboyish than unaffected sisters
• more aggressive than unaffected sisters
• increased likelihood of masculinized gender identity

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 Abnormal Development
Congenital Adrenal Hyperplasia (CAH)
• Berenbaum, Resnick, & Hines
– Given a choice of toys CAH girls chose masculine type toys (e.g., cars)
– CAH girls, compared to unaffected sisters, superior at:
• spatial manipulation task
• spatial rotation task
• disembedding task
– CAH girls did not differ from unaffected sisters on perceptual and verbal
tasks

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 Abnormal Development
Intrauterine exposure to abnormal hormone levels:
• Ehrhardt et al. (1984)
– Participants:
• 13 males, 15 females exposed to synthetic progesterone prenatally
• 22 males, 15 females exposed to progesterone and estrogen prenatally
• matched unexposed controls
– underwent comprehensive psychological exam including sex dimorphic
behavior
– Findings:
• hormone exposed males did not differ from controls
• hormone exposed females showed greater stereotyped feminine behavior (e.g.,
more interest in doll play, feminine clothing, less interest in physical play)

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 Abnormal Development
Turner Syndrome:
• affects females only, 1:2500
• “XO” instead of “XX”
• Characteristics:
– short stature (approx. 4’8”), short neck with webbed appearance, low
hairline at the back of the neck, low set ears
– fail to develop breasts at puberty
– incomplete ovary development: do not menstruate
– internal reproductive organs do not develop normally
– cognitive skills?

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 Abnormal Development
Turner Syndrome:
– cognitive skills:
• normal intelligence
• difficulty with visual spatial tasks (mental rotation), mathematics
• verbal skills normal

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 Abnormal Development
Triple X Syndrome:
• affects females only, often asymptomatic
• “XXX” instead of “XX”
• Characteristics:
– small head, tall stature
– menstrual irregularities, delayed puberty, premature menopause, infertility
– Cognitive skills?

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 Abnormal Development
Triple X Syndrome:
– Cognitive skills:
• rare: mental retardation, more “X”, more mental retardation
• delayed development of speech and language skills
• language related learning disabilities, e.g., dyslexia

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 Abnormal Development
Klinefelter Syndrome:
• affects males only, 1:500 to 1:1000, often asymptomatic
• “XXY” instead of “XY”
• Characteristics:
– small external genitalia, sterile
– feminized appearance: enlarged breasts, slightly curved hips and waist,
lack of body or facial hair, but also taller and more overweight than
unaffected fathers and brothers
– low or absent sex drive
– may be passive and/or shy
– Cognitive skills?

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 Abnormal Development
Klinefelter Syndrome:
– Cognitive skills:
• below average intelligence
• delayed onset of speech
• difficulty learning to read and write
• life-long and pervasive difficulty with language

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 Abnormal Development
XYY syndrome:
• affects males only, 1:1000
• Characteristics:
– tall, about 3 inches taller than normal on average
– severe acne
– normal fertility, normal sexual drive
– Increased aggressiveness?
– Cognitive skills?

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 Abnormal Development
XYY syndrome:
– Increased aggressiveness?
• famous serial murder case: Richard Speck, 1970s, murdered 8 women
• subsequent studies indicate inconsistent findings
– Cognitive skills:
• intelligence within normal range
• some learning and school related difficulties

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 Abnormal Development
• True hermaphrodism:
– possessing both male and female sexual anatomy
– example: one ovary, one testis, vaginal opening and
penis
• Pseudohermaphrodism:
– ovaries or testes, but not both
– if ovaries, then male external sexual anatomy
– if testes, then female external sexual anatomy

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 Abnormal Development

How should a child be raised if it (he/she) is

born with ambiguous genitalia? In other
words, what criteria should be used to
decide whether the child should be raised as
a boy or a girl?

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 Abnormal Development
Androgen Insensitivity Syndrome (AIS):
• XY genetics, raised as girls
• body unable to detect and respond normally to androgens
• complete AIS:
– normal external female appearance
– feminized external genitalia, short, blind-ending vagina
– absence of internal female genitalia - no fallopian tubes, uterus, or cervix
– undescended testes
– at puberty, normal female development (e.g., breasts)
– female gender identity, heterosexual orientation
• estradiol did not masculinize the brain!
• Explanations: culture overrides biology? Both testosterone and estradiol required to
masculinize the brain?
• incomplete AIS

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 Abnormal Development
5-alpha reductase syndrome: Guevedoces ("eggs-at-12")
• XY genetics, raised as girls
• unable to convert T to dihydrotestosterone
• Complete:
– feminized external genitalia, short, blind-ending vagina
– uterus and fallopian tubes absent - normal secretion of Mullerian
inhibiting factor
– testes, epididymis, vas deferens, seminal vesicles intact
– often misdiagnosed as AIS at birth (if ambiguous genitalia)

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 Abnormal Development
5-alpha reductase syndrome: Guevedoces ("eggs-at-12")
– at puberty: females begin to masculinize
• penis enlargement
• shoulders broaden, hips narrow
• no breast development
• facial hair growth
• adams apple becomes more prominent
– gender identity?

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 Abnormal Development
5-alpha reductase syndrome: Guevedoces ("eggs-at-12")
– Gender identity
– Imperato-McGinley et al. (1979)
• examined 38 subjects with 5 alpha-reductase deficiency
• all born with female genitalia, 18 raised unambiguously as girls
• normal plasma testosterone levels for a male
• Finding:
– during or after puberty 17 of 18 changed to male gender identity/gender
role
– suggests that exposure to normal male levels of T in utero and at puberty
contributes to male gender identity
– suggests that exposure to normal male levels of T in utero and at puberty
overrides the sociocultural influence of being raised as girls

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 Abnormal Development
Persistent Mullerian duct syndrome:
• XY
• inability to synthesis Mullerian-inhibiting hormone
• insensitivity to Mullerian-inhibiting hormone
• presence of uterus and fallopian tubes
• otherwise normal males

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 Abnormal Development
Ablatio penis:
• John Money (1975)
– reported case XY male
– penis lost at 7months due to accident, raised female
– had identical twin brother
– at age 9 female gender identity disorder
• Later follow-up:
– psychological problems
– gender identity confusion
– male gait

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 For Further Reading:
Hampson, E. Sex differences in human brain and
cognition: The influence of sex steroids in early and
adult life. Becker, Jill B. (Ed); Breedlove, S. Marc (Ed);
et al. (2002). Behavioral endocrinology (2nd ed.). (pp.
579-628). Cambridge, MA, US: MIT Press, 776pp.

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