Topic 1- Sex differences

sex determination in mamles

Gamites are the reproduction cromesones

Female XX

Male XY

Gamets are haploid

what is the gean that is responsable for turning the fetal gonad into teasteas

SRY

how dose the sex determin in humans

the SRY geane witch is located on the Y chromesones. Which turns the featal gonad ( witch cant telle if testes or oviries at the begging) into testesas

- In its absence, the gonad becomes an ovary

- Males are males because of the Y chromosome

What hormones are produced by early testes during male sex determination?

Early testes produce two types of hormones: Anti-Mullerian Hormone (AMH), which is defeminizing, and androgens, which are masculinizing.

the two types of hormones that the early testes make

Anti-Mullerian Hormone (defeminising)

Androgens (masculinising)

What is the female precursor system called?

The female precursor system in mammals is called the Müllerian system.

if internal system turns male what will happen?

anti maliaran - binad to recepters in maliran system then disintegrates (removes malria system)

andregion- for the wolffian system to be kkep and tp keep developing

Sex Determination in Mammals: External Sex Organs

Starts completely undifferntated

7-8 week after the gonad ahs turned intpo a teste or overir they are sensitive to androgens dht

Dht made by the testes required for external male apendiges

No recepters or no dht develops as a female externally

Gonad cascades to everything els

organizational hormones

effect remains after the hormone has been removed. Often occurs during a sensitive period.

activatinal hormones

effect is reversible, depending on presence or absence of hormone

Orginasuianal vs activation

-              Increased facial hair- A

-              Increased muscle mass- A

-              Brest development- A

-              Wider pelvis in woman- O

-              Wider sholdes in men – O

-              Lower voice in men- O

Puberty

- Organizational and activational role of sex hormones

- Don’t make hormeos until puberties- gonads

- Development of Secondary Sexual Characters- develop at puberty

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

onset of hormones

- During childhood, sex hormone levels are almost undetectably low

- Developmental timing mechanism starts puberty

- Sex differences in mechanisms and timing

studies suggets that pubity around 47kg

evlolutinal funactions

What is the role of the hypothalamus in initiating puberty?

The hypothalamus is responsible for kickstarting puberty by releasing hormones that signal the pituitary gland to stimulate the gonads.

in hypothalumas has collection of nerons

GABA/NPY witch inhibit KnDy nerons (kisspeptin) wich then woudl activate the GnRH nurons witch then would signal to the pituitrygland to create sex hormones

with

GnRH – realed in puses every 2 hours

We don’t know what that swich happen

witch then goes to the pituartary gland signalig to relice sex hormones

hypothalums and pituatry gland and pubity

Midline of human brain the hypothamus sits at the bottom at the brain at the bottom the grnh reasing when stimulated by the kisspeptin nerons

When ditect the gnrh ganodatroping hormin is reliced witch gose to gondaope

Hypothalumas- GnRH

Pituatry gland – gonadotropins (FSH,LH)

(GnRH)goes into the antria pituatry glands

Gonads:

- Testes: testostirosne

- Oviries: oestradiol, pojestirone

Gonadotropins- amid or goes at the gonads

folicula stimulating hormone-

female- causes foliculm to ripen

male sperm production

lutening hormone

female - inducing ovulation and formation of curpos lutum

male testostrone production

The Hypothalamus-Pituitary-Gonadal Axis: a Feedback System

-negative feedback system

keeps teasttrone around aste point

• if it is below a set point the hypothalumas will relice GnRH witch will triggar the relice of

• ganadtropins form the anteria pituatry

• witch will go toi the gonads

• whre fhs stimulate sperm production and lh produce testostrone

• witch will go to the body tissue

• witch will also go to the hypothalumas and indicate there is to much T in the blood stream withch will the tell it to stip relicing GnRH

• so drop of t

• if low wnough it starts the loop again

the mesxnstrial cycle

Four week cycle- not sesnal breeders unlike outher animals

Intractions between hypothalumas pituatry and

Graph of four different hormones

Folcule grows with stimulation of fsh wicth produces estridile

When hits certain level witch estridile

still a feed back loop but slower (around 28 days )

Stage one of teh menstarl cycle

in responce to an increase in FSH small spherases of cells called ovairian follciles begin to grow around individual egg cells (ova)

stage two of the mesnstratl cycles

the follicles begin to realeas estrogins such as estrodial

stage three of the menstral cycle

the estrocles stimulate the hypothalaumas to increase the realease of LH and FSH from the antirour pituartry

stage four of the menstral cycle

in responce to the LH surge, one of the follicles ruptures and realeses its ovum

stage five of the mensatral cycless

the rupptured folicle under the influnec of LH developes into a corpose lutem (yellow body) and begins to reales progetrone, which preapers the lining of the utrus for the implantation of a fertilized ovum

stage six of teh mestarl cycle

mean while the ovum is moved into the follopian tube by the rowing actio of ciliated cells if the ovum is not fertilised pogestrone and estrodol levels fall and walls of the utrus are sloughed off as meanstral flow and the cycle begins once again

Androgen insensitivity syndrome

- Gonads develop as testes

- Androgen receptors do not work

- Testosterone cannot do its normal job

- 46(total=al number of cromesons) , XY individuals develop anatomically as female, but without internal female genitalia

- Puberty is typically late, sometimes helped with hormone supplements

- They typically identify as women

• teastes produce enough oestragen to go thriugh female punity without peirod

- Usaly dicribed in XY individuals

- Grow up female

- The testes make endrogiles tp go through female pubertie

- Don’t have utras or oviries

- They do produce tetstostrone but doesn’t affect the secondery male atrabutes

• anti maliral is working fine - so no internal femal

• external female

5α-reductase deficiency

- 5α-reductase turns testosterone into DHT

- DHT is crucial for prenatal external genital development

- 46, XY children are born with female external genitalia, but male internal genitalia

- At puberty, the high levels of testosterone can “mimic” DHT

- They develop male genitalia (“Guevedoces”)

- After puberty, they mostly identify as men

- But when hit pubity they grow a male external genitalia – genetic component

- Can be very common in small groups in like giutamala because of interbreeding

- Built into the culture

woman with 46 XX with androgen senstivity syndrome

just lack pubity hair because testorstrone is reponsable to that but are still fertial

Congenital Adrenal Hyperplasia

21-hydroxylase deficiency

Hypothalamo-pituatary adrenal (HPA) Axis

Adrenal cortex makes cortisol

Ther is a ensymes 21 hydroxal is need ed to make the final step of cortisol

So they don’t make cortisol so they have symptoms of low cortisols

the precersers to curtisosl turn into testostrone

so you get some more male secondary cartoristics

so by giving external cortisol it will stop this loop because it is a negative feedbackloop - stops low cortasal and extra t

easy to spot in girls not in boys

teh extreanl will masculinise- have a partoial penius when born, some have such a devloped pienous thay are brought up as a boy

In the womb – anything before birth- high

When treaing CAH they gove externl cortical witch suproses the HAP loop wich stops the low cortisol and the increased testosterone

Dots get picked up everu easaly in males but in felamles dose sterigth after birth

- High levels of prenatal testosterone in girls

- Ambiguous external genitalia in girls

- Often treated once diagnosed

- Some 46,XX children assigned male at birth

- 5% of CAH girls assigned female at birth have gender dysphoria

- 12% of CA bH “girls” assigned male at birth have gender dysphoria

Shows how complex gender identity is

There are structural and functional sex differences in the brain- this can be due to the

- Hormones (activational and organizational)

- Genetics (genes on sex chromosomes)

- Environment (e.g. peers, culture,…)- shouldn’t rule out the enviremntal effects, structal bhevior may shap brain structure- prcatice of behvior- London taxi drivers

Sex Differentiation in the Brain: Mice

Mice- exsclude cultural influence

Four core genotypes and sperated them

Xy removed the sry geam meint that they have overies but have the rest of the Y geans- male geneans

XX sry- add an sry gean to make teastes but with the female geans

Are pleant of sex differences in mice

Separate the egntivcc effects and the hormone effects

Dubble sissosiation effect

Sex Differentiation in the Brain: Humans

No experimental manipulations possible

Information can be gathered from:

-            Congenital Adrenal Hyperplasia in 46,XX- high testosterone donst

-            Complete Androgen Insensitivity in 46,XY

-            Hormone treatment in transgender individuals

we can use the intesex peopole who have diifrent hormones compared to genes

dubble dissocated

can also look at transgender poeple and look at the diffrentt ages that they

Sex Differentiation in the Brain: Behavioural Differences

boys and girls have diffrent toy prefrences

boys and girls have different toy preferences- bab girl still goes for the dolls not always but on avarhge

gender specif toy prtrefrance not just a houman thing- highly controversial

looka t the paper

no different is absolutrte

sex diffrence- cah, cais and testostroene

- CAH 46,XX individuals have more masculine toy preferences- studied a lot in this context have hoig levels of testosterone mening thay have a more

CAH(exsperenecsed t in utro) - higher boy typical

Highly replicable

- CAIS 46,XY individuals typically have feminine toy preferences- play with girl toys -not purely cultural- cnat evan move yet but hard to pull apat- suggest that there is something hormonal to it

- Correlation between play style and prenatal testosterone- rare and hard to measure because mneed to mesure amniotic fulid

spcail and mental rotationn

- Men tend to be faster in spatial mental rotation tasks-

- CAH 46,XX individuals perform better than non-CAH 46,XX individuals

- CAH 46,XX individuals are more masculine in some measures than other 46,XX individual

- CAIS 46,XY individuals are indistinguishable from non-CAIS 46,XX individuals

- Suggests a role of testosterone in spatial mental rotation

- Exists in childhood and increases after pubity but not cativatinal- not corrlated with testosterone

- Some evidence that testortrone plays a part

Sex Differentiation in the Brain: Structural Differences

- Male brains are ~ 10% larger

- Female cortex is thicker (more grey matter)- same number of nerons overall

- No implication of them functing very differently- just structed slightly different

- Males have larger white matter volume & subcortical structures

- Female larger corsum collsums

- Some are done in the embvroyo

- CAIS 46,XY individuals have some features that are masculine (genetics), and some that are feminine (hormones or environment)

- Sex differences in the brain are complex and specific, and due to many different causes

- Both erly hormones but also the enviremntal factors

Sex Differences: Sexual orientation

• - One of the most extreme sex differences

  - 90-95% of human males are attracted to human females exclusively (“gynophile”)

  - 85-90% of human females are attracted to human males exclusively (“androphile”)

  - Old stats

Sex differences in the brain that co-vary with sexual orientation in humans

- SCN larger in androphile(attracted to dick exclusively) individuals (Swaab & Hofman 1988)

- INAH-3 smaller in androphile individuals (Levay 1991)

- Anterior commissure larger in androphile(attracted to dick exclusively) individuals (Allen & Gorski 1992)

- Sex differences in the brian are accutly the androfial and gynofile in the brain

Brain differences in sexul oprientation

- Could be causal to sexual orientation- farely unlicaly due to the scn could be corllialtion impatected by the sem hormopnal

- Could also be purely correlation, as indicators of other mechanisms (hormonal, genetic)

- Could be consequence of sexual orientation!

- Behvior impacts brain structure

Environmental Effects on Sex Differences- sexual orientation

- Influences on brain development (e.g. what you’re exposed to in childhood)

- Effects of practice (e.g. you are better at what you spend more time doing)

- Social effects (expectations, stereotypes,…)

- HOWEVER – little to NO evidence that this affects sexual orientation

Experience and Sexual Orientation

- Most people feel their sexual orientation has always been this way

- No good evidence to support effects of parenting, learning, etc.

- Evidence from other species

sexual orientation in sheep

- 8% of male sheep are exclusively interested in other males

- Sexually Dimorphic Nucleus (SDN) of preoptic area is smaller in these males

- Size of SDN is influenced by developmental T levels in enbrotic development

- Sexually Dimorphic Nucleus (SDN) bigger in male animals

Sex Differences in Behaviour: Activational Hormonal Effects?

-            Variations with varying testosterone levels

-            Variations with varying estradiol levels

-            Variations with the menstrual cycle

-            No evidnace to show it changes who they are interested in- just the instesity of sexual feeling

Activational role of hormones?

- No differences detected in adulthood between different sexual orientations

- Hormone fluctuations, manipulations, or treatments affect sexual motivation, but not orientation

- Gay and straight men dot have diffrnec in t

Organizational Hormonal Effects

There are two periods during development during which T is high in boys:

1.Weeks 8-24 of pregnancy

- Early: external genitalia

- Late: brain differentiation

First 3 months after birth

- potential further brain differentiation

Evidence for organizational role of hormones

• Correlations with measured prenatal hormones

• Have no direct corrlation between t and sexual orientation later

• Correlations with adult correlates of prenatal hormones

• Conditions with varying prenatal hormone levels

• Congenital Adrenal Hyperplasia (CAH)

• Androgen Insensitivity Syndrom

Correlates of embryonic T

• cognative proformance

• sex diffrence in 2d/4d rations - fingers

• Oto-acoustic emissions

Cognitive performance

Verbal abilities are better in androphile (dick) men than gynophile men

Visuo-spatial performance is worse in androphile(dick) men than gynophile men

Mental rotation is faster in gynophile women than in androphile(dick) women

Ratio of 2nd and 4th finger lengths (2D/4D)- length of the secod diget to the fourth diget

Sex differences in 2D/4D ratios (male: 0.95, female 0.97)

Early testosterone dependent

Butch lesbians have more masculine 2D/4D

No consistent finding in androphile men, but may differ between sub-groups – 2D/4D correlates with gender non-conformity (Swift-Gallant et al., Sci Rep 2021)

Doesn’t just apply to humans applies to other spices as well

Oto-acoustic emissions

When stimulated with a click, ears make a sound back

This is louder and more frequent in women (and females of other species)

Early T- dependent in other species

Gynophile women’s OAEs closer to gynophile men’s than androphile women’s

Congenital Adrenal Hyperplasia- sexual preffrance

- CAH females are also more likely to identify as gynophile

- High

- Suggesting that erly t can indicate gynophile

getic effect- twin studies

- Higher concordance in monozygotic than dizygotic twins

- Estimates from 30-100%- lost of bias so looking at neaerer 30%

- Possibly higher concordance for women than men

- Looked at minority sexual preference

gentic effect- gentic mapping

- Androphilic men often have androphilic maternal uncles

- Suggests an X-chromosome inheritance pattern

- A region of the X-chromosome has been identified as related to sexual orientation

- Regions on other chromosomes have also been identified

evolutinary concern

- Should homosexuals not have fewer offspring?- leads to lower odds of having affspring

- How does a putative genetic basis not get selected out of the population then?

Possible mechanisms for maintaining such genes:- sexuality

- Heterozygote advantage- have both copies of a gene but having one copie of the gean means you have an advantage eg sicle cell, one coppie has protection for malaria but both cause sickle cell

- Different effects in males vs females- geanes may not have the eefcts in the male compared tpo the females the andropohilic grnas in men may cause the females to have more kids

- Kin selection- if there where a geen that inflineces a gean in men the relitives carry the geane the geans will be passed on through the realitives

faternal birth order effect

The odds of havinga androfil boy the more boys that you have had as a mother

if they have older brothers by the same mouther it increases the likelihood of being gay – male older siblings

something to dowith tehe mothers response to carrying the male babbies

Fraternal Birth Order Effect:Maternal immune hypothesis

Mother’s immune response to protein neuroligin 4 Y-linked predicts probability of having male-oriented son (Bogaert et al. PNAS 2017)

There is an immune response that is built up a responec to a single proteas

influnec om gemder idntity

- Not a single phenotype

- Genetic predispositions

- Pre-transition brain differences

gneder identity

-            Gender identity evan larger than sex diffrneces than sex orientation

-            Dose not seem binary

-            Childhood dysphoria soe not always continue after pubity (dose for ~40%)

influences on gender identity

-            Not a single phenotype

-            Genetic predispositions

Pre-transition brain differences

Genetic predisposition to gender dysphoria

Stodie did on spain that looked at trans and cis people and looked at the genetic mapping off theatse people- looked like thare are specific genans with athere assosiacted with gender  disforia

large sample size

gentic mapping excerisize specfic allies that are collrated with gender dysfiria

trans males having an long version of estrogen recepterbata (ERb) and the ERa corrlated with rans

trans woman corrlated with long AR short ERa and ERb

Pre-transition brain differences

•        Brain volumes are in line with natal sex

•        MtF individuals show more feminine cortical thickness and white matter in some brain areas

•        FtM individuals show more masculine basal ganglia and some white matter tracts

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

•        Behvior can shape brain

What is the male precursor system called?

The male precursor system is called the Wolffian system

What is the initial state of sex organs in mammals?

Sex organs in mammals start completely undifferentiated.

What happens 7-8 weeks after the gonad has turned into a testis or ovary?

7-8 weeks after the gonad has turned into a testis or ovary, they become sensitive to androgens, particularly dihydrotestosterone (DHT).

What is required for the development of external male appendages?

DHT, which is made by the testes, is required for the development of external male appendages. Without receptors for DHT or if DHT is absent, the external organs develop as female.

what happerns if a male has no DHT receptors or DHT

they will not develop male external genatailia but have internal male oragns

if a male dosnt produce the anti mallirain hormone but created the androgin system

internal male and female structure

what dose a person with persistant mullerian uduct syndrom have

male exterbal genilaia with teasteas and female internal internal genitaila

XY, has internal female and internal and male externial

androgen insesntivity syndrone

A condition where a person with XY chromosomes is resistant to androgens, causing them to develop female external genitalia despite having male internal structures.

Term: What role do GABA and NPY play in puberty?

Definition: GABA and NPY inhibit the activation of KNDy neurons (kisspeptin), which are involved in activating GnRH neurons. witch realeaces GNRH into the blood streame

How frequently is GnRH released during puberty?

GnRH is released in pulses every 2 hours during puberty.

What does GnRH signal to the pituitary gland?

GnRH signals the anteria pituatary gland to release gonadtropins witch goe to the gonas FSH and LGH

what does FSH and LH do to males

FSH- sperm production

LH- testostrone production

what dose fsh and LH do to th efemale

fsh- folcule to ripen

lh- ovulationand formation of corpus luteum

a person with persistanat malirian duct syndrome has

male external with testes, male female internal gentailia

what is the exsternal genitalia of a person with androgen insensitivity syndrome are

female

androgen insesntive syndorme of XX, 46 leads to

lack of pubic hair