Biology of Sex Differentiation, Sexual Orientation, and Gender Identity Flashcards
(85 cards)
1
Q
Taboo Topics
Lecture Series #2
Biology of sex differentiation,
sexual orientation, and gender identity
A
ZACHARY WEIL
2
Q
Sexual dimorphisms in human behavior
Men VS Women
A
Higher in Males: Aggresion Schizophrenia Visuospatial abilities Autism
Higher in Females:
Depression
Nurturing Behavior
Verbal abilities
3
Q
Sexual dimorphisms in human behavior
The BIG QUESTION
A
Nature (genes, hormones)
vs
Nurture (social factors, learning, culture) ?
4
Q
Sexual dimorphisms in human behavior
-Ruth Hubbard, 1990.
A
“If a society puts half its children in dresses and skirts but warns them not to move in ways that reveal their underpants, while putting the other half in jeans and overalls and encouraging them to climb trees and play ball and other active outdoor games; if later, during adolescence, the half that has worn trousers is exhorted to “eat like a growing boy” while the half in skirts is warned to watch its weight and not get fat; if the half in jeans trots around in sneakers or boots, while the half in skirts totters about on spike heels, then these two groups of people will be biologically as well as socially different. Their muscles will be different, as will their reflexes, posture, arms, legs and feet, hand-eye coordination, spatial perception, and so on.”
5
Q
Patterns of Play Behavior
A
Girls tend to play in groups of 2 or 3, and with softer, brighter colored toys.
Even female monkeys prefer to play with dolls.
Male monkeys prefer to play with things like toy cars and trucks, monkeys don’t even drive!!!
6
Q
Strategies used to understand human behavioral sex differences
A
- Animal models
• Can experimentally control environmental conditions and manipulate hormonal conditions - People that have undergone anomalous sexual differentiation
• “Experiments of nature”
Strategies used to understand human behavioral sex differences
3. Study different cultures to identify commonalities
7
Q
parthenogenesis
A
Asexual reproduction in insects and some vertebrates (i.e. fish and reptiles)
◦ Only one sex (female) in parthenogenic animals
◦ All eggs genetically identical to mother
Although asexual reproduction is efficient, there is no genetic variation on which natural selection can act, creating a risk for extinction
8
Q
The benefit of sexual reproduction
A
Sexual reproduction produces more genetic variation and evolutionary flexibility
9
Q
Relationship between sexual dimorphism and the mating system
A
Monogamous species (single mating partner) are LESS sexually dimorphic (different) than polygamous species (multiple mating partners)
Monogamous: Males don’t need to have so much more androgens, than the females because the males have much less competition.
Example:
Prairie voles are monogamous and the male & females are physically similar and both pretty nurturing to offspring.
Elks are polygamous, and the males are much bigger, have antlers, and are much more aggressive.
10
Q
Sexual selection favors sexual dimorphisms
A
Humans are mildly to moderately polygynous and display several sexual dimorphisms consistent with other polygynous species
11
Q
Proximate questions
A
HOW do sexual dimorphisms arise?
12
Q
Sexual Differentiation =
A
the process of becoming a male or female
13
Q
How do sexual dimorphisms arise?
A
- Chromosomal Sex
- Gonadal Sex
- Hormonal Sex
- Morphological Sex
- Behavioral Sex
14
Q
Chromosomal Sex
A
F: XX, homogametic
M: XY, heterogametic
15
Q
Gonadal Sex
A
Related to gametic sex.
- F: ovaries, eggs
- M: testes, sperm
16
Q
Hormonal Sex
A
F: high estrogen, low androgen
M: high androgen, low estrogen
17
Q
Morphological Sex
A
differences in body type, CNS, and effector organs (i.e., muscles)
18
Q
Behavioral Sex
A
discriminated on the basis of male and female typical behaviors
19
Q
Mammalian Sexual Differentiation
A
Begins at fertilization with chromosomal sex and depends on whether the sperm that fertilizes the egg carries an X or a Y sex chromosome (Sex determination)
- F: XX, homogametic
- M: XY, heterogametic
Males determine the sex of the offspring; Females can only
20
Q
Mammalian sexual differentiation:
Step 1: development of the gonads
A
Gonads: internal organs
◦ F: ovaries
◦ M: testes
Each individual is identical: whether XX or XY, have identical bipotential primordial gonads (germinal ridge)
◦ SRY gene on Y chromosome –> testis-determining factor (TDF) –> medulla (middle) of germinal ridge becomes testes
◦ No SRY –> no TDF –> cortex (outside) of germinal ridge becomes ovaries
Occurs approx. 6 weeks after conception
Partial expression of SRY gene -> incomplete gonadal
differentiation –> ovotestis
SRY can be express in one gonad and not the other —> testis develops on one side and an ovary on the other
21
Q
Mammalian sexual differentiation
Step 2: development of the accessory sex organs
A
Accessory sex organs connect gonads to outside environment
All individuals until the 3rd month have precursors to both male and female accessory sex organs
◦ Wolffian system develops into seminal vesicles, vas deferens, epididymis
◦ Müllerian sytem develops into fallopian tubes, uterus, cervix
Male development requires two hormones from the testes
◦ Testosterone promotes development of the Wolffian system
◦ Mullerian Inhibitory Hormone prevents Mullerian system from developing
Female development does NOT require hormones
◦ In the presence of ovaries or absence of gonads –> Mullerian system develops and Wolffian system regresses
22
Q
Two processes at work in the typical development of the accessory sex organs
A
Masculinization:
induction of male traits (testosterone & 5α-DHT)
Demasculinization: removal of the potential for male traits
Feminization: induction of female traits
Defeminization: removal of the potential for female traits (Mullerian Inhibitory Hormone)
23
Q
Female development does NOT require hormones
A
Female system is low-key the default system
24
Q
Males:
development of the external genitalia
A
- penis, scrotum and testes
- Androgens are responsible for male external genitalia, particularly 5α-dihydrotestosterone, which is converted from testosterone by the enzyme 5α-reductase
25
Females:
development of the external genitalia
labia, clitoris and outer vagina
No hormonal activity required for development of female genitalia
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Standard development of the external genitalia
Although the two sexes are generally binary, genital development can fall anywhere along this continuum leading to ambiguous genitalia
27
T ----> 5α-DHT
5α-reductase
28
Disorders of Sex Development (DSD)
Anomalies in the process of sexual differentiation
Result of chromosomal or hormonal abnormalities
“Experiments of nature”
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No record of viable organism that has a single Y chromosome
DSD: sex chromosome abnormalities
30
Turner Syndrome
XO
– Female typical external
appearance and genitalia.
– Ovaries underdeveloped and don’t make steroid hormones.
– Require hormone treatment at puberty.
– Other hormonal abnormalities that slow growth as well as hearing loss, intellectual disability, kidney dysfunction.
DSD: sex chromosome abnormality
31
Klinefeltersyndrome
XXY
– Appear male but genitalia are underdeveloped
– Usually sterile because of reduced sperm production
– Gynecomastia, disproportionally long limbs
– Severe learning disabilities
32
XYY
– Male appearance but usually sterile
– Above average height
– Below average intelligence
33
Congenital Adrenal Hyperplasia (CAH)
XY males are unaffected
Genetic (XX) females exposed prenatally to excess endogenous androgens from the adrenal glands resulting in masculinized genitalia with an ‘intersex’ appearance
Masculinization of the external genitalia in genetic females can also be caused by prenatal exposure to exogenous androgens, ex. Diethylstilbestrol (DES) or Medroxyprogesterone acetate (MPA)
34
5α-reductase deficiency
* XY males that lack the 5-alpha-reductase enzyme which converts Testerone --> 5-alpha-dihydrotestosterone (androgen responsible for masculinization of the external genitalia)
* Have ambiguous external genitalia, but the development of testes and accessory sex organs isn't affected (because Testerone and Mullerian Inhibitory Hormone function normally)
* Raised as girls but at puberty, Testosterone causes development of secondary sex characteristics and masculinization of external genitalia
35
Organizational/Activational Hypothesis
William C. Young (1899-1965)
Behavioral sex differences result from:
1) differential exposure to hormones that act early in development to organize neural circuitry underlying sexually dimorphic behaviors
2) differential exposure to sex steroid hormones later in life that activate the neural circuitry previously organized
36
Young’s classic experiment
Mating behavior in rodents is sexually dimorphic:
◦ Females: lordosis
◦ Males: mounting
Rodent mating behavior under control of gonadal steroids
◦ Castration of adult males stops mounting behavior and Testosterone restores it . However, adult females
given Testosterone do not display increased mounting behavior (demasculinized)
◦ Removing ovaries from adult females stops lordosis which is reinstated with ovarian steroids.
However, treating castrated males with ovarian hormones does not lead to lordosis
(defeminized)
37
Young’s classic experiment
Process
Hypothesis:
Hormonal events early in development are important for adult reproductive behavior
Experiment:
◦ Testosterone given to pregnant guinea pigs
◦ As adults, female offspring were ovarietcomized and given:
1) Estrogen+Progestins to stimulate female sexual behavior
2) given Testosterone to stimulate male sexual behavior
Results:
◦ Female guinea pigs exposed to androgens prenatally display reduced lordosis and increased mounting
◦ No effect of early androgen exposure on male sexual behavior
Conclusion:
The potential for masculine or feminine behavior is organized by early exposure to hormones
38
Sensitive or Critical Period
A period of time when an animal is maximally sensitive to the organizing effects of hormones to permanently change morphology and/or
behavior.
Usually within the prenatal and/or perinatal period, depending on species
◦ Rats: first 10 d after birth
◦ Guinea pigs: halfway though their 69 day gestation period
◦ Humans: end of 1st trimester and first few weeks of 2nd trimester
Once the critical period has ended, no amount of hormones can have an organizational effect
39
Organizational Effects of Hormones
Exposure to androgens in early life permanently organizes the brain to permit the later expression of masculine behavior in response to activational effects of hormones.
In the absence of androgens, the brain and behavior develop in a female-typical fashion.
40
Organizational and Activational Effects of Hormones
In addition to mating behavior, many adult behavioral sex
differences in rats (i.e., aggression, parental behavior and emotional behavior) are organized by hormones during a critical period and activated by hormones in adulthood.
Organizational (
41
Mechanism by which androgens masculinize the brain
Androgens play a direct role in the masculinization of the human brain
But, in many animals, aromatization of testosterone into estradiol masculinizes the brain
Depending on the species, females are protected from estradiol by:
• α-fetoprotein binds estrogen and prevents maternal estradiol from masculinizing the female brain
• The placenta
42
aromatization
testosterone into estradiol
43
Control of Ovulation
Gonadal function and
reproductive behavior is cyclic in females but tonic in males
Males:
Exposure to androgens
early in development permanently alters the neuronal
circuitry involved in the release of GnRH surges from the
hypothalamus forever destroying the potential for female positive feedback effects
Females: without exposure to
androgen, the neural circuitry
involved in GnRH surge
generation is spared
44
Surge center=
Anteroventral periventricular nucleus (AVPV)
45
Pulse center =
Medial basal hypothalamus
46
Environmental Influences on Mammalian Sexual Differentiation
* Intrauterine environment
* Maternal stress
* Differences in maternal care
* Exposure to environmental chemicals
47
Effects of the intrauterine environment
Female rat pups' position in the
uterine horn can impact her
physiology and behavior as an
adult
2-M females are more aggressive, less attractive to males, and have longer ovarian cycles
48
Effects of maternal stress
```
Male offspring of mothers stressed during pregnancy:
• Produce less androgen
• Have impaired mating behavior
• Have certain parts of the
nervous system that are more
female typical
• Show more parental behavior
• Are less aggressive
• Exhibit demasculinized rough
& tumble play
```
49
Effects of Maternal care
• Mother rats spend more time licking male pups than female
pups because they prefer the chemosensory cues associated
with male pups urine
• Mother rats who are rendered unable to smell their pups do not lick their male pups more and these males show altered patterns of male sexual behavior as adults suggesting that males require maternal licking to develop normal adult sexual behavior
• Females who are licked more as pups are more attentive
mothers later
50
Endocrine disrupting chemicals (EDC)
mimic the effects of estrogen, androgen, or thyroid hormones
example: DDT, Atrazine, Bisphenol A (BPA)
51
Atrazine
Commonly used herbicide
Does not affect adult frogs but modest levels affects sexual development in frogs producing
testicular abnormalities
52
Bisphenol A
| (BPA)
• Effects of EDC in humans include:
Males: Double the rate of cryptorchidism and hypospadias
(urethra opens on underside of penis) in boys, triple the rate of testicular cancer, reduced sperm counts
Females: earlier onset of puberty
53
Environmental sex determination
No sex chromosomes in some species of reptiles
Temperature involved in sex determination
Effects of temperature can be overridden by steroids
◦ If eggs are incubated at male-producing temperatures but given estrogen, then females develop.
◦ If eggs are incubated at female producing temperatures but are given androgen, males develop.
54
Sequential hermaprodites:
animals that begin life as one
sex then change to the other sex as adults
Seen in many species of fish in
response to their social
environment
Example: clownfish
If Mom dies, Dad becomes a female!
55
Intersex
an individual with elements of
| both sexes but most typically refers to gonads or genitals.
56
Transsexual
an individual that believes that they are trapped in the ‘wrong’ sex.
57
Sexual orientation
the preferred partners for romantic and sexual relationships.
58
Do Genes Play a Role in Sexual
Orientation or Sexual Identity?
Homosexuality
The male siblings of a gay male are between 20-25% likely to be gay. Similar findings for the siblings of lesbians. (4-6%
in general population)
The dizygotic male twin of a gay male has a 15-20% chance of being gay.
Monozygotic twins have 65% concordance.
There is also evidence that gay men have more maternal-line gay male relatives. (implicates the X chromosome specifically
Xq28 but not at all clear the mechanism).
Strangely, the more older brothers an individual has the more likely that they will be
gay (chances increase by about a third with each older brother).
59
Do Genes Play a Role in Sexual Orientation or Sexual Identity?
Transsexuality
don’t know yet…
60
The Phall-o-meter
When bodies don’t fit into our pre-existing notions of male and female, we will force them to, even if it involves a knife.
Clitorises that are longer than .9cm and penises that are shorter than 2.5cm must be fixed
61
CAIS
Complete androgen insensitivity syndrome
Genetic XY individuals with no ability to respond to androgen signaling.
Almost always raised as women.
Usually don’t know about the conditon until they don’t begin to menstruate.
Vast majority experience “heterosexual” orientation and don’t usually experience gender-related issues.
62
5-alpha-reductase deficiency
Do not process testosterone into dihydrotestosterone
Recall that testosterone is a weak androgen and doesn’t signal strongly on it’s own.
XX females are usually unaware of this condition.
XY individuals are typically sexed as females at birth but often have enlarged clitorises.
At puberty, higher testosterone concentrations cause development of male secondary sex characteristics, and about 60% will choose to live as heterosexual males.
63
Cloacal Exstrophy
Fairly rare birth defect with the bladder partially outside of the abdomen and a partially or completely absent penis
Typically (at least in the past) surgery and hormone therapy started at birth and these kids were raised as girls.
However, only about 50-60% of these individuals will elect to continue living as girls into adulthood.
64
Congenital Adrenal Hyperplasia
Genetic mutation causes the adrenal to be unable to produce glucorticoid hormones. This leads to excess production of adrenal androgens.
Usually not detected in XY males until much later in life.
Has little or no effect on sexual differentiation or orientation
In females, this is usually detected at birth when girls have masculinized genitals.
Exogenous glucocorticoids can be given at birth to stop the process, but some brain sexual differentiation has already occurred.
This is the largest predictor of female to male transexuality with CAH girls 100-300x more likely to report transsexuality. *Still only 1-3%
65
The Curious Story
| of Olympian Stella Walsh
Stella Walsh was a dominant sprinter of the 1930s and 1940s, the winner of 41 U.S. Championships in various events.
Born in Poland, she
emigrated to America and became a high school star in Cleveland.
Competing for Poland at the 1932 Olympics she won gold in the 100-meter dash.
At the Berlin Olympics of 1936 she lost at 100 meters to her bitter rival Helen Stephens; a controversy followed when Walsh's supporters hinted that Stephens was too fast to be a woman.
German doctors examined Stephens and announced she was truly female.
Walsh continued to compete
as an amateur until 1954 and was inducted into the U.S. Track & Field Hall of Fame in 1975.
5 years later, she was killed by a stray bullet during a robbery at a Cleveland shopping center.
An autopsy surprised everyone by showing that Walsh had male
genitals and both male & female chromosomes -- a condition known as mosaicism.
66
Unusual case of
| David Reimer
Can a boy be transformed into a
girl?
Summer 1965. In a Winnipeg hospital, Janet Reimer's gives birth to twin sons, Bruce & Brian.
But within 6 months, both boys develop difficulty urinating. The doctors suggest they be circumcised.
The doctors had chosen an unconventional method of circumcision, one in which the skin would be burned.
The procedure goes horribly wrong, and Bruce's penis is burned so badly it can't be repaired surgically.
The family sought help from many physicians. The Reimers saw a television profile of an American doctor and his theories on sex & gender. Dr. John Money of Johns Hopkins University argued that boys caught early enough could be raised to be girls. Nurture, not nature, determines a child's gender, the doctor argued.
The Reimers took Bruce to Money’s clinic at Johns Hopkins.
At the age of 21 months, Bruce's testicles were removed. What remained of his penis was left, not to interfere with his urinary tract.
When Bruce was released
from hospital, his parents were told to raise him as a girl.
The family was told not to divulge anything to anyone.
They went home with a girl they called Brenda.
Unhappy childhood, felt different, not accepted by boys or girls
When told at 14 about his
past, decided to have surgery to return being a male.
Later, he married a woman who already had children.
Ultimately, David committed suicide.
67
DIRECTION OF HAIR WHORL
Klar (2004) reports that 30% of gay men show an anti-clockwise hair whorl, compared
with 8% of straight men.
The genetic mechanism connects with that responsible for handedness (hence hemispheric brain specialization).
68
SEXUALLY DIMORPHIC NUCLEI IN THE HYPOTHALAMUS
```
LeVay (1991) found differences
between gay and straight men
in certain nuclei in the
hypothalamus that differentiate
men & women and are
concerned with sexual behavior.
```
These were primarily the
interstitial nuclei of the anterior
hypothalamus (INAH-3) and the
suprachiasmic nucleus (SCN).
Because many of his post- mortem subjects had died of
AIDS, he was obliged to show
that this did not account for his
results.
69
WELL CONNECTED BRAINS
Witelson (2008) have shown that that isthmus region of the corpus callosum (the conduit
between the two halves of
the brain) is larger in gay
than straight men.
This supports the idea that gay
men (like women) have less
structural & functional asymmetry in the brain than
straight men.
70
AMYGDALA CONNECTIONS
Using PET & MRI scans, Savic & Lindstrom (2008) showed that the amygdala is wired more for fight-flight reactions (action) in straight men & lesbians, and more to
emotional responses such as anxiety (feelings) in gay men & straight women (see widespread connections on left side).
```
They also found more rightward asymmetry in
straight men (+12cc) and lesbians (+5cc), whereas the two sides were much the same volume in gay men & straight women.
```
71
GRAY MATTER IN THE PERIRHINAL CORTEX
Using structural MRI,
Ponseti (2007) found that lesbian women had less gray matter in the left perirhinal cortex than heterosexual women.
In this respect, they were
more like men.
This area is involved in olfactory & visual processing, but the functional meaning of the finding is not clear.
No such differences were
found between gay & straight men.
72
TASK PERFORMANCE PROFILES
Straight women & gay men excel in verbal fluency and memory.
Lesbians are better than straight women at spatial tasks
(Rahman, Wilson & Abrahams, 2004).
73
PREPULSE INHIBITION IN LESBIAN WOMEN
Startle reactions (strength of eye-blink) are reduced if the startle stimulus (sudden loud noise) is preceded by a weaker version of itself.
PPI occurs less in women, but lesbian women respond more like men.
Since this is an involuntary reaction, it suggests hardwiring rather than social learning.
74
FINGER RATIOS
Men typically have a shorter forefinger than ring finger.
In women, they are much the same or reversed.
This seems to be a marker of
exposure to prenatal testosterone.
Williams (2000) found that gay & straight men were similar in 2D:4D, but lesbians were inclined toward the male pattern.
Relationships were
stronger on the right hand
compared with the left.
There was a significant
tendency for men with older brothers to have a masculinised finger ratio regardless of their sexual orientation.
75
```
Harry Benjamin International Gender
Dysphoria Association (HBIGDA)
```
Standards of Care for Gender Identity Disorders – 2001
Eligibility Criteria for Hormone Therapy
1. 18 years or older
2. Demonstrable knowledge of social & medical risks and benefits of hormones
3. Either
A. Documented real life experience for at least 3 months
OR
B. Psychotherapy for at least 3 months
76
Transgender Hormone Therapy
Heredity limits the tissue response to hormones
More is not always better
77
Female to Male Treatment Options
No Hormones
Depotestosterone:
Testosterone, Enanthate, or Cypionate
100-200 mg IM q 2 wks (22g x 1 ½” needles)
Transdermal Testosterone:
Androderm or Teestoderm TTS 2.5-10mg qd
Testosterone Gel:
Androgel 50, 75, or 100 mg to skin qd
Testosterone Pellet:
Testopel- implant 6-10 pellets q month
78
Testosterone Therapy
| Permanent Changes
Increased facial and body hair
Deeper voice
Male pattern baldness
Clitoral enlargement
79
Testosterone Therapy – Reversible Changes
Cessation of menses
Increased libido, changes in sexual behavior
Increased muscle mass / upper body strength
Redistribution of fat
Increased sweating / change in body odor
Weight gain / fluid retention
Prominence of veins / coarser skin
Acne
Mild breast atrophy
Emotional changes
80
SURGICAL OPTIONS FOR FTMs
Mastectomy
Continue CBE/SBE on residual tissue
Hysterectomy/oophorectomy
Consider adding low dose estrogen or estrogen vaginal cream
Genital reconstruction
◦ Phalloplasty
◦ Metoidioplasty
81
Male to Female Treatment Options
No hormones
Estrogens:
Premarin 1.25-10mg po qd or divided as bid
Ethinyl Estradiol (Estinyl) 0.1-1.0 mg po qd
Estradiol Patch 0.1-0.3mg q3-7 days
Estradiol Valerate inj. 20-60mg IM q2wks
Antiandrogen
Spironolactone 50-100 mg po bid
Progesterone
Not usually recommended
82
Estrogen Treatment May Lead To
Breast Development
Redistribution of body fat
Softening of skin
Loss of erections
Testicular atrophy
Decreased upper body strength
Slowing or cessation of scalp hair loss
83
Sex difference in masculine and feminine indexes was clear in the drawings by unaffected boys and
girls.
Their drawings do not or mostly do not contain
characteristics typical of the opposite sex.
Boys tend to draw mobile objects & mechanical objects with dark or cold colors and often use bird’s-eye-view composition when they draw pictures.
Girls like to draw human motifs (esp girls & women), flowers, and butterflies with light
& warm colors and tend to arrange motifs in a row on
the ground.
Analyses were made on the drawings of girls with congenital adrenal hyperplasia (CAH) and unaffected
boys & girls, using masculine and feminine indexes.
Compared with those of unaffected girls, the pictures of CAH girls more strongly showed masculine characteristics.
The feminine index for the pictures of CAH girls was significantly lower than that for unaffected girls, while the
masculine index for CAH girls was significantly higher
than that for unaffected girls.
Furthermore, the masculine
index for CAH girls was not significantly different
from that of unaffected boys.
These results suggest that
androgen exposure during fetal life may contribute to shaping masculine characteristics in children’s free drawings.
84
Androgen Insensitivity Syndrome (AIS) also known as testicular feminization mutation (TFM) in rodents
• XY genotype
* Gonads develop as testes which release Testosterone and Mullerian Inhibitory Hormone
* Genetic mutation prevents the formation of androgen receptors which disrupts normal development of the Wolffian system and external genitalia
• Anti-Mullerian hormone still has a defeminizing effect
• Normal-appearing female external gentalia, female appearance and female gender identity

• Usually not discovered until puberty
85
Hermaphrodites
Individuals who have both ovaries and testes
| • Extremely rare
