Sexual Differentiation and Puberty

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Sexual Differentiation and Puberty
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Sexual Differentiation
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Ovulation
Corpus luteum
Oocyte
Cumulus mass
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Determination of Genetic Sex

• Genetic sex is determined by the chromosomal
  complement of the sperm
• All oocytes are 23 X
• Half of sperm are 23 X
• Half of sperm are 23 Y
• Genetic sex is determined at the time of
  fertilization

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Fertilizing Oocyte
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Fertilized Embryo Determination of Genetic Sex
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Embryology

• Primordial germ cells migrate to the gonadal
  ridges during the 4th-5th weeks of gestation
• Recognizable testicular development antecedes
  ovarian development by 5-6 weeks
• Anatomically separate structures give rise to
  internal genitalia
• External genitalia are derived from common anlagen

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Early embryologic development of gonads Migration
of germ cells
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EmbryologyMale

• First sign of testicular development is
  appearance of Sertoli cells that migrate to form
  testicular cords
• Testicular cords later enclose the germ cells
• Leydig cells form the interstices between the
  seminiferous tubules, discernible at 60 days
• Leydig cells secrete testosterone
• Sertoli cells secrete ABP, inhibin and
  Anti-Mullerian Hormone (AMH)

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EmbryologyFemale

• Development occurs later than testes
• Not until the 10th-11th week are structures
  recognizable as ovaries
• Primary oocytes develop into primordial follicles

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Sexual Differentiation Timeline
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Development of Internal Genitalia

• Derived from Wolffian ducts in male
• Derived from Mullerian ducts in female
• Both of these ducts develop alongside the
  mesonephric duct
• Mesonephric duct is part of developing urinary
  tract
• Without gonadal influence, development will
  proceed and result in female internal genitalia

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Sexual differentiation Male Female differences
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Development of Internal GenitaliaMale

• Requires testosterone for differentiation of
  Wolffian ducts
• Mullerian ducts regress under influence of
  Anti-Mullerian Hormone (AMH)
• AMH is a protein hormone, similar to inhibin,
  produced by Sertoli cells
• AMH also called Mullerian Inhibiting Factor (MIF)

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Development of Internal GenitaliaFemale

• Female internal genitalia developed from the
  Mullerian ducts
• In the absence of either ovarian or testicular
  signals, development of normal female structures
  occurs

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Wolffian and Mullerian Ducts
Paratubal cysts
Gardners duct cysts
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Development of External Genitalia

• External male genitalia develop under influence
  of dihydrotestosterone (DHT)
• DHT is a potent androgen derived from 5?
  reduction of testosterone
• Female external genitalia develop in the absence
  of gonadal signals

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External Genitalia Common embryologic anlagen
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Testicular Development

• The presence of the Y chromosome does not assure
  that testicular development will occur
• There are 46 XX males and 46 XY females
• A region of the Y chromosome called SRY (sex
  determining region of Y) has been identified
• SRY contains key genes that code for testicular
  development
• If SRY is absent, testes do not develop

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Sexual DifferentiationGenetic Factors

• SRY
• testes determining factor
• SOX9 MIS-R
• activate MIF
• SF-1 WT1
• transcriptional factors
• DAX1
• inhibitory regulator

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Gonadal Dysgenesis

• Many clinical syndromes exist in which the gonads
  do not develop normally
• In most cases, this will result in a female
  phenotype
• These individuals do not progress through normal
  puberty and do not develop secondary sexual
  characteristics

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Puberty
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Puberty

• Hypothalamic-pituitary-gonadal axis
  differentiates and functions during fetal life
  and early infancy
• Fluctuations in gonadotropins and gonadal
  steroids occur commonly throughout first 6 months
  of life and up to 2 years of age
• May be associated with development of ovarian
  follicles (cysts)
• Levels of gonadotropins and gonadal steroids
  decline to very low levels during first 1-2 years
  of life and remain suppressed until onset of
  puberty (juvenile pause)

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Fetal Reproductive Activity Female
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Fetal Reproductive Activity Male
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PubertyHormonal Onset

• Puberty does really represent initiation of
  pulsatile GnRH and gonadotropins, but
  reactivation from suppression
• Nocturnal amplification of gonadotropin release
  occurs in early puberty
• By late puberty, pulsatile LH pattern is stable
  throughout the 24 hour clock and similar to adults

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Onset of Puberty Nocturnal LH pulses
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Chronology of Puberty Male
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Tanner Stages Male
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Female Puberty

• Thelarche breast development
• Adrenarche (pubarche) pubic and axillary hair
• Menarche menstrual bleeding

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Chronology of Puberty Female
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Tanner Stages Female
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Menarche

• First episode of menstrual bleeding
• Last event in female puberty
• Decline in age of menarche occurred in last
  century
• No further decline over last 25 years
• Maybe nutritionally related

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Age at Menarche
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Menarche

• Obesity accelerates menarche
• Malnutrition delays menarche
• Chronic illness delays menarche
• Vigorous physical exercise delays menarche

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Reproductive Capacity

• 50-90 of menstrual cycles during first 2 years
  after menarche are anovulatory
• Less than 20 are anovulatory by 5 years after
  menarche
• Onset of fertility in males is difficult to
  detect. Spermaturia occurs at approximately 14
  years of age

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Skeletal Growth

• Girls grow 5.5 cm/yr until pubertal growth spurt
• Girls grow 8 cm/yr during growth spurt (1-2
  years)
• Boys grow 5 cm/yr until growth spurt
• Boys grow 10 cm/yr during growth spurt
• Final height difference about 13 cm

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Muscular Growth

• Muscular growth lags behind skeletal growth by
  about 1 year
• Largely driven by androgen
• Muscular strength in females does not appreciably
  change after menarche
• Muscular strength in males increases until about
  age 25

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Fat ChangesMales

• Boys lose fat, especially in limbs during puberty
• Boys gain truncal fat in late puberty
• Reach approximately 12 body fat by completion of
  puberty

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Fat ChangesFemales

• Girls have continuous increase in body fat
  throughout puberty
• Rapid and extensive accumulation of fat in arms,
  lower trunk and hips
• Reach approximately 18 body fat by completion of
  puberty