Sex Determination and Differentiation

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Sex Determination and Differentiation
Page 97-116, 126-135
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Levels of sex determination
Chromosomal sex
Gonadal sex
Hormonal sex
Morphological sex
Behavioral sex
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Mammalian sexual differentiation
TDF/SRY
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Hormones determine sexual development

• The female pattern is default
• Embryonic ovaries are quiescent
• Presence of ovaries or absence of any gonads -
  female pathway

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The Müllerian and Wolffian Systems
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• Feminization and demasculinization
• Masculinization and defeminization

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Sexual differentiation in mammals
Female
Male
Chromosomal sex
XX XY
TDF/SRY
No Yes
Gonadal development
Ovary Testis
Local T secreted
No Yes
Müllerian duct dev.
Yes No
Wolffian duct dev.
No Yes
T in circulation
No Yes
External genitalia
Female Male
Behavior
Female Male
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Anomalies in females

• Turner Syndrome XO - treat with gonadal hormones
  in the mid-teens to induce puberty
• Exposure to androgens
• Exogenous - environment or steroid treatments
• Endogenous - ovaries or adrenal glands
• e.g. congenital adrenal hyperplasia (CAH) fetal
  adrenal glands produce androgens masculinizing
  genitalia in females

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Anomalies in males
Testicular feminization mutation (TFM) lack of
functional androgen receptors - normal appearance
of female external genitalia, sexed and reared
as girls
5?-reductase deficiency Genetic males born with
ambiguous genitalia and small undescended testes,
sexed and reared as girls until puberty when
androgens masculinize the body
Trisomic anomalies possess an extra chromosome.
XXY (Klinefelter
syndrome) considered as males at birth, Y is
sufficient for masculinization, -- sterile due to
reduced sperm production. XYY considered as
males at birth, sterile, and an additional Y is
associated with aggressiveness
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Hormone effects on sexually dimorphic behavior
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Mating in rats
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• Hypothesis
• Hormonal events early in development are
  responsible for induction of masculine and
  feminine behavior and for shifting of
  probabilities of masculine and feminine mating
  behaviors in females and males.

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gestation
T
high T
low T
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Androgen given early in life

• less lordosis behavior
• more mounting behavior in response to T
• no effects on males

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Youngs speculations

• Distinction between organization and the
  activation effects
• Critical periods during perinatal development
• Organization of the neural tissues mediating
  mating behavior is analogous to development of
  the genital tracts

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The organization/activation hypothesis

• Exposure to sex steroid hormones in early
  development permanently organizes or establishes
  the neural substrate that will be needed for
  subsequent male- or female-typical behaviors.
• The same hormones activate, modulate, or inhibit
  the behavioral functions in adulthood by acting
  upon these organized neural structures.

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The Study of Freemartinism
Freemartin a sterile, female twin of a male
found in cattle, sheep, goats, and pigs.

• A female calf (XX) born as a twin to a normal
  male
• 90 of females having male twins are freemartins
• The external genitalia is of the female type
• The gonads resemble testes more than ovaries

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• Hormonal hypothesis androgens or other
  masculinizing factors are able to reach to the
  female through the vascular connections of the
  placenta, and affect the internal anatomy of the
  female

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Rat pups gestating in uterus
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The intrauterine position affects physiological
and behavioral functions of female rodents

• Inter-female aggression is higher in 2-M than in
  0-M females.
• 0-M females are more attractive to males than 2-M
  females.
• 2-M females have longer ovarian cycles than 0-M
  females.

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Hormonal control of ovulation

• Gonadal functions females-cyclic and males-tonic
• Reproductive behaviors fellow similar patterns
• Regulations the hypothalamus-pituitary-gonadal
  axis with feedback mechanisms

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A negative feedback regulation
Ovaries
Estrogen
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Female
Male
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Sex differences in the regulation of ovulation

• The pituitary glands?
• An androgen exposure
• A critical period for androgen organization
• The hypothalamus is in control
• Perinatal androgens destroy the GnRH surge
  center in the hypothalamus and permanently
  eliminate the potential for a positive feedback
  effect.

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A feedback regulation of the hypothalamus-pituitar
y-gonadal axis
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The purse and surge centers
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• Androgens in a critical period permanently
  organize the brain.
• The same hormones activate adult behaviors by
  acting on the organized neural substrates.
• The masculinizing effects of T on behavior is
  dependent upon its conversion to E.
• The ?-fetoprotein binds to E to protect females
  from masculinization.