Sex differences

Definitions

• Gender: Cultural identity

• Sex: biology

chromosomes - sex determination

• gametes = reproductive cells

• Females have XX

• Males have XY

• Father determines whether cell is fertilised with an X or Y (50/50 chance)

• Mother always provides X

• Sex is determined by the presence/ absence of the Y chromosome

SRY gene

• identified in 1990s

• Located on Y chromosome

• Turns the fetal gonad (undifferentiated sex cell) into a testis (2 testes)

• Testis determining factor

• In its absence, the gonad becomes an ovary

Hormones - sex determination

• early testis produce 2 types of hormones:

  • anti-mullerian hormone (defeminising): responsible for getting rid of the mullerian system (female). Maintains internal male features. Someone with persistent duct syndrome (only affect men) will have male external genitalia but male and female internal genitalia as it doesnt influence wolffian system but will make mullerian system female

  • Androgens (masculinising): e.g. testosterone - maintains external genitalia and wolffian system (male). Someone with androgen insensitivity syndrome will lack functional receptors for androgens to bind to when maintaining external features so will have female external genitalia

• In the absence of these hormones, female sex organs develop (primary sexual characters)

Development of Internal sex organs

• Mullerian system: develops into internal female sex organs - ovaries, fallopian tube, uterus, vagina etc

• Wolffian system: develops into male internal sex organs - will turn into the tube from testes to urethra

Development of external genitalia

• 7th-8th week of fertilisation we are sensitive to androgens e.g. DHT (dihydrotestosterone) which is made by the testes and will turn external anatomy male

• No DHT leads to external anatomy turning female

Actions of hormones

• organisational:

  • often occurs during a sensitive period

  • Once hormone has made a change, the change will remain regardless of if the hormone is removed

  • E.g. wider pelvis in women and wider shoulders and lowering of voice in men

• Activational:

  • effect is reversible, depending on presence/ absence of hormone (Only effected when hormone is active)

  • Occurs during and after puberty

Puberty/ sexual maturation

• Organisational and activational role of sex hormones

• Development of secondary sexual characteristics

• Pubic and axillary hair are androgen (androstenedione) sensitive in both males and females

Onset of puberty

• During childhood, sex hormone levels are almost undetectably low

• Developmental timing mechanism starts puberty

• Sex differences in mechanisms and timing

• evidence has linked women starting their period with weight reaching 47kg as well as genetically linked onset

Hypothalamus and Pituitary gland - puberty onset

• gonadotropin releasing hormone (GnRH) in the hypothalamus triggers puberty by being released into the bloodstream to the anterior pituitary gland and once it is detected, puberty hormones start being produced by the gonads into tissue

• Positive/ negative feedback influences the subsequent release of hormones and how it influences behaviour

• happens when GABA/ NPY neurons are inhibited

• Males who take anabolic steroids (mimic testosterone) can lead to testes making lower amounts of testosterone causing hypothalamus to produce less GnRH which can cause the testes to shrink as there is no stimulation from FSH and LH (in females it would cause secondary sexual male characteristics)

Gonadotropins

• Hormones that go to the gonads (ovaries/ testes) including:

  • follicle stimulating hormone (FSH): produces sperm in males and causes follicles to ripen in women

  • Luteinising hormone (LH): produces testosterone in males and induces ovulation/ formulation of corpus luteum in women

The menstrual cycle

• lasts approx 28 days

• Increase in FSH causes ovarian follicles to grow around an individual egg cell (ova)

• The follicles then begin to release estrogens such as estradiol Which stimulate the hypothalamus to increase the release of LH and FSH from the anterior pituitary

• In response to the LH surge, one of the follicles ruptures and releases its ovum Which develops into a corpus luteum (yellow body) and begins to release progesterone which prepares the lining of the uterus for the implantation of a fertilised ovum

• The ovum moves into the fallopian tube by the rowing action of ciliates cells - if it is not fertilised, progesterone and estradoil levels fall and the walls of the uterus are sloughed off as menstrual flow and the cycle begins again

Variation in sexual differentiation

• androgen sensitivity syndrome

• 5a-reductase deficiency

• Congenital adrenal hyperplasia

Androgen insensitivity syndrome

• gonads develop as testes (male) but androgen receptors don’t work so testosterone cannot do its normal job so will develop anatomically as female but remain with male internal genitalia

• Puberty is typically late, sometimes helped with hormone supplements

• People suffering with this will typically identify as female as they will develop female secondary characteristics too due to lack of testosterone so will appear female but biologically are male

5a- reductase deficiency

• 5a reductase turns testosterone into DHT which is crucial for prenatal external genital development in men

• 46, XY children suffering with this will be born with female external genitalia but male internal genitalia

• At puberty, the high levels of testosterone can mimic DHT, causing the development of male genitalia (guevedoces)

• Will tend to identify/ appear female before puberty but identify/ appear male after puberty

Congenital adrenal hyperplasia

• hypothalmo-pituitary adrenal (HPA) axis adrenal gland makes cortisol requiring 21-hydroxylase but without this, there will be no cortisol so the adrenal gland will make testosterone instead

• Treated using external cortisol leading to the suppression of the HPA axis to reduce testosterone

• Causes high levels of prenatal testosterone in girls which can cause ambiguous external genitalia So some of these children assigned male at birth

• 5% of these girls assigned female at birth have gender dysphoria but only 12% assigned male have gender dysphoria

Sex differentiation in the brain

• can be structural or functional

• Due to hormones (activational vs organisational), genetics (genes on sex chromosomes) and environment (practice of behaviour can change the brain)

Mccarthy and Arnold - sex differences in mice

• found the different sex chromosomes effect habit formation, alcohol preference, aggression and nociception by swapping genes/ chromosomes

• Found gonads effect sex behaviour, LH secretion, aggression and nociception by swapping hormones

• Shows how changing chromosomes/ hormones can demonstrate sex differences

Sex differentiation in humans

• can’t be manipulated

• Information can be gathered from congenital adrenal hyperplasia, androgen insensitivity and hormone treatment in transgender individuals but aren’t controlled for so may be impacted by confounding variables

Alexander and Hines - sex typical toys in monkeys

Found infant vervet monkeys had sex typical toy preference (female and doll, male and car)

Sex toy preference differences

• different toy preferences

• CAH 46, XX have more masculine toy preferences

• CAIS 46, XY have more feminine toy preferences

• Correlation between play style and prenatal testosterone (hormonal influence) - higher fetal testosterone = more likely to play with male toys (auyeung et al)

Sex spatial metal rotation task differences

• men tend to be faster

• CAH 46, XX perform better than other 46, XX

• CAIS 46, XY are indistinguishable from 46, XX

• Suggests a role of testosterone in spatial mental rotation

• More et al found males are more likely to play with LEGO/ blocks when they’re young so are better because of their environment not biology

Structural sex differences

• male brains are ~10% larger

• Female cortex is thicker (more grey matter) - doesn’t necessarily mean they have more neurons as males have bigger brains to account for that

• Males have larger white matter volume (axons) and subcortical strictures/ corpus callosum

• CAIS 46, XY have some features that are masculine (genetics) and some that are female (hormonal/ environment)

• Sex differences in the brain are complex and specific and due to many different things

Sexual orientation sex differences

• one of the most extreme sex differences

• 90-95% males are attracted to females exclusively (gynophile)

• 85-90% females are attracted to males exclusively (androphile)

• CAH females are more likely to identify as gynophile (balthazart)

Sexual orientation and brain differences

• super charismatic nucleus (SCN) larger in androphiles - swaab and hofman

• INAH-3 (located in hypothalamus) found to be smaller in androphiles - levay (only studied people who died of AIDS)

• Anterior commissure found to be larger in androphiles - Allen and gorski

• Unsure if these differences are causal to sexual orientation or a consequence

Origins of sex differences in brain and behaviour

• experiential/ cultural effects

• Activational hormonal effects

• Organisational hormonal effects

• Genetic effects

Environmental effects on sex differences

• influences brain development (what you’re exposed to in childhood)

• Effects of practice (better at what you spend more time doing)

• Social effects (expectations/ stereotypes)

• But there is little to no evidence that it effects sexual orientation as most people feel it has always been this way

Sexual orientation in sheep

• 8% male sheep are exclusively interested in other males

• Sexual dimorphic nucleus (SDN) of pre optic area is smaller in these males (similar to females)

• Shows size of SDN is influenced by developmental T levels (lower = smaller SDN)

• Could SDN be the equivalent of humans INAH3

Activational hormonal effects on sex differences

• variations in testosterone/ estradiol levels

• Variations with the menstrual cycle

• No differences detected in adulthood between different sexual orientations

• Hormone fluctuations, manipulations and treatments can affect sexual motivation but not orientation

Organisational role of hormones

• Most evidence points towards a role of prenatal testosterone in developing as a gynophile adult

• two periods during development (before/ just after birth) where T is high in boys:

  • weeks 8-24 of pregnancy (early= external genitalia, late= brain differentiation

  • First 3 months of life - potential further brain differentiation

Organisational hormonal effects on sex differences

• correlations with prenatal hormones - although this is hard to measure as retrieving amniotic fluid is risky

• Congenital adrenal hyperplasia (CAH)

• Androgen sensitivity syndrome

Correlates of embryonic Testosterone

• cognitive performance

• Ratio of 2nd and 4th finger lengths (2D/4D)

• Oto-acoustic emissions

Sex differences and Cognitive performance

• verbal abilities better in androphile men (similar to females)

• Visuo-spatial performance is worse in androphile men (similar to females)

• Mental rotation is faster in gynophile women (similar to men)

• Suggests people who have the same sexual orientation share similar characteristics

Sex differences and 2D/ 4D ratios

• males 2nd digit is slightly shorter than their 4th (0.95) vs females who have similar lengths (0.97)

• Suggested to be early testosterone dependent

• Butch lesbians have more masculine 2D/4D ratios

• No consistent finding in androphile men but may differ between sub-groups - 2D/4D correlates with gender non-conformity (swift-gallant et al) e.g. males who present themselves as more feminine during development (linked to testosterone) tend to have more female 2D/4D ratios

Oto-acoustic emissions effects on sex differences

• when stimulated with a click, ears make a sound back but this has been found to be louder and more frequent in women

• Early T dependent

• Gynophile women OAEs closer to gynophile men’s

Genetic effects on sex differences

• twin studies

• Genetic mapping

• Concerns from an evolutionary angle

• Fraternal birth order effect

Twin studies

• higher concordance in MZ twins - suggests a genetic component to sexual orientation

• Twins grow up in similar environments but if MZ are more similar it suggests a genetic component

• Concordance rates estimate from 30-100% And tend to be higher for women

Genetic mapping

androphile men often have androphile maternal uncles suggesting this is inherited from the mothers side and an x-chromosome inheritance pattern to sexual orientation

Evolutionary concerns

• should homosexuals have fewer offspring and how does this sexual orientation not get selected out of the population?

• Possible mechanisms for maintaining the homosexuality gene:

  • heterozygote advantage - only one copy of the gene may be required to pass on

  • Different effects in males vs females

  • Kin selection - someone else in the family who carries the gene but isn’t gay can pass it on

Fraternal birth order effect/ maternal immune hypothesis

• Balthazart found you’re more likely to be a gay man if you have more brothers (from the same mother) suggesting a maternal immune response

• Bogaert et al found Mothers immune response to protein neuroligin 4 Y-linked predicts probability of having an androphilic son

Sexual orientation conclusions

• biological developmental influences

• No influence is absolute

• Influenced by a number of different factors

Gender identity

• has an even larger sex difference than sexual orientation

• Isn’t binary

• Childhood gender dysphoria doesn’t always continue after puberty (but does for approx 40%)

Influences on gender identity

• not a single phenotype/ description

• Genetic predispositions

• Pre transitional brain differences

Genetic predispositions to gender dysphoria

• Fernandez et al looked at trans men/ women and compared them to cis en/ women

• Mapped their genetics and found genes associated with gender dysphoria

• Found trans men had long ERB and alpha ERa alleles

• Trans women had long AR, short ERB and alpha ERa

Pre transitional brain differences and gender identity

• brain volumes are in line with natal sex

• Male to females show more feminine cortical thickness and white matter in some brain areas

• Female to male individuals show more masculine basal ganglia and some white matter tracts

• Some aspects of brain anatomy are different from both cis males and females

• Suggests difficulties of gender dysphoria can lead to brain changes before transition or perhaps having these differences are what causes gender dysphoria

Conclusions

• genetic and hormonal factors cause sexual differentiation

• Different aspects of brain and behaviour can be masculinised/ feminised leading to a wide diversity of combinations of gendered traits