Chapter 11
Sexual Development and Differentiation
Learning Outcomes
01 Able to define terms related to gender determination.
02 Distinguish gender at the different levels.
03 Explain factors and mechanism involved in gender determination.
04 State and explain gender ambiguities.
05 Identify factors related to gender ambiguities.
Introduction
• Sex
• Genetic sex - chromosomes.
• Anatomical sex - internal and external genitalia.
• Sexual identity - one’s identity as male or female.
• 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.
• Androgyny/hermaphrodism
• Sex: possessing both male and female reproductive organs.
• Gender: possessing both male and female qualities.
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)
• The 23rd pair are the sex chromosomes
• Male : XY
• Female : XX
6
3 waves of cells
migrate : green, blue
and PGC (red)
Cell derived from
Coelomic epithelia
Origin of
Mesonephric primordia
Sex Cells
Origin of
Sex Cells
Sexual Differentiation
• Mullerian-inhibiting hormone - inhibits further development of Mullerian ducts
• Primordial germ cells- gamete
• Coelem epithelial cells – development of these cells depend on Sry gene.
• Expressed Sry – cells proliferate and penetrate, form primitive sex cords (testis).
• Sry activity on the Y chromosome converts an indifferent gonad into a testis via the
actions of Sox9 suppressing Foxl2, whereas the absence of its activity results in an
ovary.
• Mesonephric cells – 3 major cell types (vasculature tissue, Leydig cells and cord).
SRY gene
• The SRY gene is found on the Y chromosom
stimulate production of AMH @ MIH (Sertoli cells)
Stimulate PGD – amplifies Sox9 expression
Stimulate Fgf9 – chemotactic factor – cells migrate
Suppress Foxl2 expression
• Prevent the development of female reproductive structures (uterus and fallopian
tubes).
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.
Normal Prenatal Development:
Internal & External Genitalia
• Sexual differentiation: Gonadal development
• 8 weeks gestation
• Y chromosome contain SRY genes
• Male (XY) : expression of SRY genes causes undifferentiated sex glands to
develop into testes
• Female (XX): lack of SRY genes causes undifferentiated sex glands to develop
into ovaries
Internal Genitalia 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)
• Absence of mullerian-inhibiting hormone - mullerian ducts develop
• Absence of testosterone - wolffian ducts degenerate
Internal
Genitalia
Development
External Genitalia Development
• Sexual differentiation: Genital development
• Male (XY)
• Testosterone (leydig cells) 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
External
Genitalia
Development
9 week old embryo
11 weeks Pregnant
1. Anus
2. Labioscrotal folds
3. Legs
4. Genital tuber
7. Urethral groove
8. Urogenital folds
BOY GIRL
Baby Gender Prediction
• By the 20th week of pregnancy the external genitalia changes
are done.
• If your baby is cooperating and is positioned in a favorable
way, his or her sex can be identified as early as the 16th to
18th week of pregnancy on ultrasound.
• The male fetus may show a round bulbous area within the
genital area which is the scrotum and penis.
• The correct visualization of any fetal part depends on many
factors such as fetal position, amount of amniotic fluid and
thickness of the abdominal wall.
• 3D scans can make it easier to see the gender of baby.
Codes for
formation of
Testes
SRY gene on the
Y Chromosome
Leads to
development
of mature male
reproductive
system
Testosterone
leads to the
natural
development
of the
Female reproductive organs
leads to
development
of mature
female
reproductive
system
Estrogen and Progesterone
Role of the Brain for Normal Prenatal
Development
• Sexual differentiation:
• Male:
• Testosterone secreted into the blood reaches the brain
• Testosterone converted to estradiol and dihydrotestosterone in the brain
• Estradiol masculinizes the brain structures and functions that are associated
with male-typical behaviors and cognitive patterns.
• Female:
• Alpha-fetoprotein binds to estradiol
• Prevents estradiol from entering the brain
• Protects female brains from being masculinized by estradiol
Brain Differences Between Men and
Women
• Neuroscience researches into sex differences in brain structure had confirmed that brain
size and structure are different in males and females
Men Women
• Spatial rotation tasks • Perceptual speed - rapidly identifying matching items
• Mathematical reasoning tasks • Mathematical calculation tasks
• Navigation through a route • Greater verbal fluency
• Guiding or intercepting projectiles • Recalling landmarks from a route
• Faster at precision manual tasks
Normal Prenatal Development: Genetics
Gyno Sperm: Paternal DNA dissolves or is destroyed before it can fuse with the egg.
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
• Normal intelligence and verbal skills
• Difficulty with visual spatial tasks (mental rotation), mathematics.
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:
• Rare: mental retardation, more “X”, more mental retardation
• Delayed development of speech and language skills
• Language related learning disabilities, e.g., dyslexia
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
Abnormal Development
Abnormal Development
Klinefelter Syndrome
• Cognitive skills:
• Below average intelligence
• Delayed onset of speech
• Difficulty learning to read and write
• Life-long difficulty with language
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
• 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
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
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?
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!
• Incomplete ais
Abnormal Development
5-alpha reductase syndrome: Guevedoces (“penis-at-12")
• XY genetics, raised as girls.
• Unable to convert testosterone to dihydrotestosterone (DHT).
• 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).
Abnormal Development
5-alpha reductase syndrome: Guevedoces (“penis-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
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