Chapter 3: Sex Determination and Differentiation Flashcards
3 Strategies used to understand human behavioral sex differences
- Animal models.
Can experimentally control environmental conditions and manipulate hormonal conditions. - People that have undergone anomalous sexual differentiation.
“Experiments of nature” - Different cultures to identify commonalities.
Causes of Sex Differences
The BIG QUESTIONS
Ultimate questions:
WHY do sexual dimorphisms arise?
Proximate questions:
HOW do sexual dimorphisms arise?
Why sex?
Asexual reproduction in insects and some vertebrates (i.e. fish and reptiles): parthenogenesis
There’s only one sex (female) in parthenogenic animals
All eggs genetically identical to mother
Pros & cons of asexual vs. sexual reproduction
Efficiency vs. evolutionary flexibility
Why sexual dimorphism?
Relationship between sexual dimorphism and mating system.
Sexual selection favors sexual dimorphisms.
Humans are mildly to moderately polygynous and display several sexual dimorphisms consistent with other polygynous species (Size, ornamentation)
Parthenogenesis
A type of asexual reproduction in which eggs can develop into offspring without fertilization.
polygynous
The condition or practice of having more than one wife at one time.
A mating pattern in which a male mates with more than one female in a single breeding season.
Sexual differentiation
the process of becoming a male or female
Although the two sexes are generally binary, genital development can fall anywhere along this continuum leading to ambiguous genitalia
Mammalian Sexual Differentiation
Begins at fertilization with chromosomal sex and depends on whether the sperm that fertilizes the egg carries an X or Y sex chromosome (Sex determination)
- F: XX, homogametic
- M: XY, heterogametic
- Chromosomal Sex (XX or XY)
- Development of the Gonads
- Development of the Accessory Sex Organs
- Development of the External Genitalia
Mammalian sexual differentiation:
development of the gonads
Gonadal sex: internal organs
Early in ontogeny, XX and XY individuals 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
SRY can be express in one gonad and not the other
Mammalian sexual differentiation:
development of the accessory sex organs
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
Wolffian system
develops into seminal vesicles, vas deferens, epididymis
Müllerian system
develops into fallopian tubes, uterus, cervix
Male development requires 2 hormones from the testes
1) Testosterone:
Promotes development of Wolffian system.
Masculinizing effect.
2) Anti-Mullerian hormone:
Prevents Mullerian system from developing.
Defeminizing effect.
Female development does NOT require hormones
In the presence of ovaries or absence of gonads, Mullerian system develops and Wolffian system regresses
“DEFAULT” program
???
Masculinization
The induction of male traits.
Feminization
The induction of female traits.
Demasculinization
The removal of the potential for male traits.
Defeminization
The removal of the potential for female traits.
Mammalian sexual differentiation:
development of the external genitalia
**Males:
penis, scrotum.
Androgens are responsible for male external genitalia, particularly 5α-dihydrotestosterone, which is converted from testosterone by the enzyme 5α-reductase.
**Females:
labia, clitoris, and outer vagina.
No hormonal activity required for development of female genitalia
Female sex is ‘default’ ?
The idea that embryos develop as females unless they receive specific genetic instructions to become males may be over simplified
Female mice with mutation of Wnt-4 gene develop male sex organs
Wnt-4 normally acts to suppress the male sex system by preventing the production of testosterone and inhibiting the development of the Wolffian duct
Deleted Wnt-4 –> activation of the male pathway in female mice
Over-expressed Wnt-4 –> male feminization, indicating that it is able to block male development even in the presence of SRY.
Argues against the assumption that female development results from a lack of active signalling.
Male-typical gene expression is likely ACTIVELY REPRESSED by epigenetic mechanisms (biochemical gene silencing).
Chromosomes may also directly influence sex differences in brain and behavior
SRY mRNA has been detected in mouse brain (not just testes) during development.
May have other roles.
A number of genes are differentially expressed between male and female brains prior to gonadal formation
X chromosome inactivation
One X-chromosome randomly inactivated in each cell of females
Gene dosage equivalence with males
Females are a mosaic
Is inactivation random?
Is it complete?
X chromosome escapees
Not all genes on x-chromosome are inactivated, so females sometimes get ‘double the dose’ of certain genes
That means, for these genes, females have 2x the gene, 2x the protein as males.
X- Escapees even differ between tissues!
Disorders of Sex Development (DSD)
Anomalies in the process of sexual differentiation
Result of chromosomal or hormonal abnormalities
“Experiments of nature”
There’s been NO record of viable organism that has a single Y chromosome
Turner Syndrome (XO):
Female typical external appearance and genitalia
Ovarian underdevelopment
Require hormone treatment at puberty
Other hormonal abnormalities that slow growth as well as hearing loss, intellectual disability, kidney dysfunction
Severity depends on which parent they get their X from, it’s better if they get it from mom.
Klinefelter syndrome (XXY):
Appear male but genitalia are underdeveloped
Usually sterile because of reduced sperm production
Gynecomastia, disproportionally long limbs
Severe learning disabilities
XYY:
Male appearance but usually sterile
Above average height
Below average intelligence
Increased Aggression?
Congential Adrenal Hyperplasia (CAH)
XY males are unaffected
Problem with synthesis of hormones in adrenal gland (which makes stress hormones).
ANDROGENS
Genetic (XX) females have masculinized genitalia with an ‘intersex’ appearance
Behavioral masculinization too…
Congenital adrenal hyperplasia (CAH) =
A genetic deficiency that results in the overproduction of androgens by the adrenal glands. This syndrome has no reported ill effects in males, but causes various degrees of masculinization of the external genitalia in females, which may lead to erroneous assignment of sex at birth.
5α-reductase deficiency
XY males that lack the 5-alpha-reductase enzyme which converts Testosterone to 5-alpha-dihydrotestosterone (the androgen responsible for masculinization of the external genitalia).
Normal brain male development.
Have ambiguous external genitalia but development of testes and accessory sex organs not affected (because testosterone and anti-mullerian hormone function normally)
Raised as girls but at puberty, testosterone causes development of secondary sex characteristics and masculinization of external genitalia
Typically have male gender identity from childhood
Prenatal testosterone
Guevadoces of the Dominican Republic
Steroid 5alpha-reductase deficiency in man:
an inherited form of male pseudohermaphroditism
Androgen Insensitivity Syndrome (AIS),
a.k.a., testicular feminization mutation (TFM) in rodents
XY genotype
Gonads develop as testes which release T and AMH
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
UNAMBIGUOUS Female gender identity (no androgens acting on brain development)
Tons of hormone, bad receptors
Almost always retain identity as a woman, are usually very feminine.
Hermaphrodites
Individuals who have both ovaries and testes
Extremely rare
Organizational/Activational Hypothesis
Behavioral sex differences result from:
- differential exposure to hormones that act early in development to organize NEURAL circuitry underlying sexually dimorphic behaviors. SOFTWARE
- differential exposure to sex steroid hormones later in life that activate the neural circuitry previously organized. HARDWARE
William C. Young (1899-1965)
Young’s classic experiment
William C. Young (1899-1965)
**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 T restores it.
- However, adult females given T 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).
Young’s classic experiment..
continued
Hypothesis: hormonal events early in development are important for adult reproductive behavior
Experiment:
T given to pregnant guinea pigs
As adults, female offspring were ovariectomized and given:
1) Estrogens & Progestins to stimulate female sexual behavior
2) given T 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
**Guinea pigs are more like humans than rats and mice in their prenatal development.
This is why they are often used in studies of this type.
Sensitive or Critical Period
A period of time when an animal is maximally sensitive to 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 days after birth
Guinea pigs: halfway though their 69 day gestation period
Humans: end of first trimester and first few weeks of second trimester
Once the critical period has ended, no amount of hormones can have an organizational effect
We now think that adolescence may be an additional mini-critical period for sex specific brain development.
Especially for feminization
Sensitive period: not just when hormones usually act, but when hormones can even have any type of permanent effect.
Activational Effects
Adulthood
No sensitive or critical period
Transitory
Organizational Effects
Occurs before the brain matures
Critical period
Relatively permanent
Organizational and Activational Effects of Hormones
Many adult behavioral sex differences in rats are organized and activated by hormones:
aggression, parental behavior, and emotional behavior
Organizational (
For Females:
Organizational: nothing
Activational: Estrogens & Progestins
Organizational and Activational 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 & behavior develop in a female-typical fashion.
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 (basically all non-primate species do something different), females are protected from estradiol by: Alpha fetoprotein (mostly) The placenta (a little)
But not the spotted hyena!
Hyenas don’t have alpha fetoprotein, so females in this species are pretty masculine-like.
Masculinization and defeminization of brain and behavior are 2 different processes:
Both processes (in rats) depend on estradiol
Estradiol induces masculinization of the preoptic area via a downstream mediator (prostaglandin E2).
Treating baby female rats with the prostaglandin masculinizes copulatory behavior (masculinization), but leaves maternal behavior (feminization) intact.
Masculinized but not De-Feminized because need activtional hormones are still needed.
Treating baby males with inhibitor of prostaglandin synthesis leaves them de-masculinized but not feminized
CONCLUDE: 2 processes occurring side by side
In rodents, estrogens derived from androgens are masculinizing to BRAIN.
In humans, just androgens!!
!!!!
Two stage model for organizational effects on behavior
Perinatal
Adolescent
Environmental Influences on Mammalian Sexual Differentiation
Intrauterine environment
Maternal stress
Differences in maternal care
Exposure to environmental chemicals
Effects of the intra-uterine environment
Female rat pups’ position in the uterine horn can impact her physiology and behavior as an adult
Fetal girls pups situated between two fetal males are affected by the males’ hormones
2-M females are more aggressive (some masculination), less attractive to males (different behavior? different pheromones?) and have longer ovarian cycles (their brains are a bit different)
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 and tumble play
Mom is more stressed… Fetal boys are less masculine and less de-feminized.
Mom’s stress hormones, glucocorticoids may interfere with fetal boy androgens
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
Male pups are more demanding of and more receptive to mom’s care
Endocrine disrupting chemicals (EDC) mimic the effects of estrogen, androgen or thyroidple: DDT
mimic the effects of estrogen, androgen or thyroid hormones
example: DDT
DDT:
Flame-Retardent.
Stays around in the environment.
Can act on hormone receptors.
Atrazine
Endocrine disrupting chemical
Commonly used herbicide
Does not affect adult frogs but modest levels affect sexual development in frogs producing testicular abnormalities
Amphibians in particular are very sensitive to hormone disruptions relative to other animals, likely because their metamorphosis process is driven by hormones
Potent organizational effects
Bisphenol A
Excreted estrogens derived from birth control pills
Effects of EDC in humans include:
Males: Double the rate of cryptorchidism (no testes) and hypospadias (urethra opens on underside of penis) in boys, triple the rate of testicular cancer, reduced sperm counts
Females: MUCH earlier onset of puberty
Body fat is one of the triggers for puberty, so larger girls tend to start puberty earlier.
But the obesity issue is not enough to explain these huge effects across the board.
Greasy birth control hormones urinated into the water supply
Environmental sex determination
NO sex chromosomes in some species of reptiles
Temperature involved in sex determination
Effects of temperature can be overriden by steroids
If eggs are incubated at male-producing temperatures but given estrogen, then females develop.
If eggs are incubated at female producing temps but are given androgen, males develop.
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 (Nemo lol)
“If Mom dies, Dad becomes a female!”
