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CMHC201 > Lecture 20: Biology of sex > Flashcards

Lecture 20: Biology of sex Flashcards

1
Q

what is sex?

A

biological classification based on gonads, reproductive system and genetic

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2
Q

what is gender?

A

gender identity is a person’s sense of identification as male, female, both or neither. society based concept not biological-based

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3
Q

how does sex differ from gender?

A

sex is more of a binary system, it is either a male gamete or a female gamete

gender identity is more fluid

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4
Q

what are the biological sex characteristics?

A
  1. Genetic (XX or XY)
  2. Gonads (Ovary or a testis)
  3. Hormones (which sex steroid is dominant)
  4. Internal reproductive anatomy
  5. External genitalia
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5
Q

what are the 2 stages of sex determination?

A

Primary sex determination:

  • is the development of the gonads
  • and is genetically determined
  • occurs during embryogenesis
  • there is no default state (if there is no signal there will be no ovaries or testes

Secondary sex determination:

  • is the development and maturation of associated structures
  • determined by gonadal hormones
  • occurs during embryogenesis and puberty
  • the default state is female (no signal coming from gonads = female formation)
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6
Q

where do gonads arise from?

A

Primary sex determination
- involves the formation of either ovary or testis from the bi-potential gonad

  • gonads develop from a “bi-potential tissue” - called the urogenital ridge (this forms into the testis or ovaries)
  • the tissue is the same in males and females until gonadal sex determination (approx 6 weeks)
  • then the bi-potential gonad cells adopt a sex-specific fate

XX cells - Theca cells, granulosa cells

XY cells - Leydig cells, Sertoli cells

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7
Q

How is male development triggered?

A

SRY is the only gene on the Y chromosome needed to trigger male development

SRY = sex-determining region of the Y chromosome

  • it is expressed only on the Y chromosome from 41 days after fertilisation and a transcription factor is made
  • This starts a cascade of expression of all the genes on other chromosomes which are needed for testis development
  • Two ‘X’ chromosomes are needed to repress the male development and drive the development of the ovaries
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8
Q

What is the breakdown of sex determination by day?

A

day 0 = Fertilisation (Y or X chromosome)

day 41-42 = Expression of SRY from the Y chromosome (XY) OR repression of the testicular pathways (XX) and development of ovaries

**2 X chromosomes are required for full ovarian development and maturation

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9
Q

what is secondary sex determination?

A

Secondary sex determination involves the development of the female and male phenotypes

The phenotype is driven by the response to hormones secreted by the ovaries and testes

2 phases:

1) In the embryo during organogenesis
2) Puberty

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10
Q

What is the development of the reproductive tract for males and females?

A

Males:

The mesonephric (wolffian) duct because the vas deferns of the male reproductive tract

Females:

The paramesonephric (mullerian) duct becomes the uterus and uterine tube of the female reproductive tract

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11
Q

how to gonads drive the production of the reproductive tract?

A

In secondary sex determination the default sex is female.

But testes make 2 hormones which allow the production of the reproductive tract:

1) Anti-mullerian hormone (AMH)
- is produced by sertoli cells in the testis
- it inhibits the development of the Mullerian/paramesonephric ducts and the female reproductive tract which stops it into developing into a uterus

2) Testosteron
- is produced by Leydig cells
- it is required for the development of the Wolffian/mesoneprhic ducts, and the male reproductive organs

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12
Q

What are DSDs?

A

Disorders of sex determination!
- variations in sex determination

  • they are congential conditions in which the development of chromosomal, gonadal and anatomical sex is atypical
  • i.e. when the 5 biological sex characteristics aren’t all male or all female

can be due to:

  • disruption of gonadal development
  • variations related to androgen excess or insensitivity
  • issues with genetics or hormone action
  • mismatches between gonads and reproductive organs and external genitalia
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13
Q

What are examples of DSDs?

A
  1. Klinefelter syndrome
  2. Gonadal Dysgenesis
  3. Androgen insensitivity syndrome
  4. Congenital adrenal hyperplasia
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14
Q

what is Klinefelter syndrome?

A
  • chromosome abnormalities
  • 47 XXY (example of trisomy, is genetically male)
  • 1 in 600 males, diagnosed at puberty
  • Disruption of the HPG axis
  • low range of normal for testosterone
  • low body hair, muscle mass, facial hair
  • high estrogen, increased breast growth
  • infertility

What happens:
Y chromosome -> so has SRY -> so can develop testis -> so can develop AMH -> so the mullerian ducts degenerate bu there is low testosterone production which leads to variable masculinisation and more feminised bodies

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15
Q

what is gonadal dysgenesis?

A

a geneitc issue with sex chromosomes
- aka Swyer’s syndrome

  • XY (genetically male)
  • No SRY expression or mutation in pathway downstream of SRY
  • ‘Streak’ gonads
  • They don’t develop ovaries or testis as there is no signal, but female is the default so they will develop female phenotype: female genitalia, female reproductive structures including uterus and uterine tubes
  • no sex steroids produced in puberty
  • can’t go through puberty without medical intervention

What happens:
- Y chromosome but no SRY -> so no testis -> no AMH -> mullerian ducts remain -> female reproductive tract; low testosterone -> wolffian ducts regress

  • most identify as female but are genetically male
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16
Q

what is androgen insensitivity syndrome?

A

a genetic issue with autosomal chromosome

  • XY (genetically male)
  • 1 in 100,000
  • Mutation in androgen receptor (can’t respond to androgens)
  • feminsation/ambiguous genitalia
  • no mullerian ducts so has no uterus

What happens:
Y chromosome -> has SRY -> so can develop testis -> so will produce AMH -> so mullerian ducts regress (partly) -> will have partial female reproductive tract (no uterus); will make testosterone but no androgen receptor -> wolffian ducts regress -> underdeveloped male genetalia and a more feminised phenotype

17
Q

what is congenital adrenal hyperplasia?

A

genetic issue with autosomal chromosom

  • adrenal gland condition
  • gene mutation in a key enzyme results in excessive androgen production instead of cortisol because androgen and cortisol are produced the same way until an enzyme signals androgen to turn into cortisol
  • XX: ambiguous birth genitalia
  • XX and XY: rapid growth, early puberty, early fusion of growth plates, tall child/short adult (males are less affected as they have high androgen anyway)

What happens:
XX -> no SRY -> no testis -> no AMH -> mullerian ducts remain -> female reproductive tract develops; high adrenal androgens are insufficient for wolffians ducts retention, but may cause clitoral enlargement

18
Q

is there a male vs female brain?

A

there are sex differences is aspects of the brain but both sexes brains are more similar than they are different

19
Q

what is useful about sex differences in the brain?

A

sex-differences could help to explain differences in susceptibility to neurodevelopmental disorders e.g. ASD

other disorders with gender bias:

Male:

  • ADHD
  • autism
  • dyslexia
  • stuttering
  • tourettes
  • early onset schizophrenia

Female:

  • late onset schizophrenia
  • anorexia
  • bulemia
  • multiple sclerosis
  • PTSD
  • anxiety
  • depression
20
Q

what are structural differences in the brain?

A
  • male brain is larger, 11-14% due to differences in physical size
  • female brain has greater cortical thickness (folds of the cerebral cortex with layers of neurons)
21
Q

what are the differences in brain growth during childhood?

A
  • female brain reaches “peak volume” earlier than the male
  • females go through pruning process earlier
22
Q

what are the hypothesised reasons for sex differences in the brain?

A
  • genetic (Y’s and X chromosome)
  • circulating hormones
23
Q

what evidence do we have about the brain, hormones and sex differences? how to we study it?

A

much of the evidence for hormones and their role in pre-natal sex-dimorphic brain development comes from animal studies

androgens influence brain development and this may explain some structural and behavioural differences between the sexes

Human studies:

Girls with congenital adrenal hyperplasia:

  • report reduced satisfaction with female gender roles
  • reduced female-typical gender identity
  • prefer to play with boy toys

Boys with congenital adrenal dysplasia:

  • show no alterations in gender identity
  • exposed to androgen concentrations similar to those without CAH (prenatal)
  • this suggests that prenatal androgen exposure could play a role in gender identity development in healthy children

CMHC201 (15 decks)

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