Descent of scrotal testes and temperature regulation

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Descent of scrotal testes and temperature
regulation
Rebecca C. Bott, MS Erica K. Gee, BVSc, PhD BS
640 Fall 2006
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Importance of scrotal descent

• Failure of testis descent into the scrotum is one
  of the two most frequent male reproductive
  pediatric complications.
• 3 mature male newborns (up to 4-5)
• 1 in 1 year old boys
• 30 prevalence in premature boys

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Importance of scrotal descent

• Undescended testes leads to an increased
  incidence in testicular cancer.
• 15-fold increase in unilateral crytporchidism
• 30-fold increase in bilateral cryptorchidism
• Descent is essential for normal fertility as
  spermatogenesis can be greatly affected.

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Scrotal Animals
Scrotal Swine, Cattle, Goats, Sheep, Felids,
Canines, Primates, Rodents Non-scrotal Birds,
Reptiles, Elephants, Dolphins, Fish
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Comparative view of testes
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Testis development migration

• Intra-abdominal
• Inguino-scrotal

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Testis development migration
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Gubernacular development

• Thick ligamentous structure comprised of
  condensed mesenchymal cells.
• Peritoneal cells infiltrate the gubernaculum at
  the levels of the inguinal cannal.

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Role of gubernaculum in descent

• Gubernaculum penetrates the inguinal ring and
  grows rapidly from the distal end.

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Role of gubernaculum in descent

• Once the testes are in the inguinal region the
  first phase of testicular descent in complete.

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Role of gubernaculum in descent

• The gubernaculum begins to regress. This
  regression is the driving force pulling testes
  into the scrotum.

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Orchestrators of testis descent

• In 1973 scientists removed one or both testes
  from dogs and found abnormal gubernacular growth.
  
• Testes or testis extract must be present to
  stimulate gubernacular growth in vivo and in
  vitro.
• descendin

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Role of INSL3

• Produced and secreted by Leydig cells prior to
  mesenchymal proliferation and gubernacular
  growth.
• Transgenic INSL3 -/- mice are cryptorchid with
  undeveloped gubernaculum.

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Role of INSL3
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Role of INSL3

• Many labs have found implications for INSL3 in
  cryptorchidism
• Very few clinical cases of cryptorchidism have
  been linked to mutations in INSL3 or its
  receptor.

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Role of Androgens

• Androgens have been implicated as the primary
  factors involved in the second phase of testis
  descent.
• Androgens are important for gubernacular bulb
  development.
• When given anti-androgens, gubernaculum growth
  and testis descent is inhibited. This is easily
  reversed by addition of androgens.
• Timing of the actions of androgens is critical!!!

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Additional Factors
We know more about what we dont know, than what
we do know.
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Problems with testicular descent

• Cryptorchidism
• Aetiology is multifactorial
• Risk factors include low birth weight when
  adjusted for gestational age, twinning, maternal
  exposure to estrogen in 1st trimester
• May be heritable, some breeds appear more at risk
• Surgical correction, prevent loss of germ cells
  in humans
• Induced promotion of rapid, lean muscle growth
  investigated as a form of contraception in
  humans

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Problems with testicular descent

• Ectopic testes
• Inguinal hernia
• Rabbits and rats have a patent inguinal canal
  throughout life

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Thermoregulation

• Maintenance of testicular temperature of 2-7C
  below body temperature is essential for
  spermatogenesis
• Five main anatomical features for
  thermoregulation
• Thin scrotal skin, often hairless, lots of sweat
  glands
• Tunica dartos
• Pampiniform plexus
• Cremaster muscle
• Absence of fat

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Thermoregulation

• Scrotum thermosensor, cooler and protector
• Supports testes
• Bilobed sac, 4 major layers
• Skin sweat glands and thermosensitive nerves

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Thermoregulation
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Scrotum as a swamp cooler

• Scrotum has many sweat glands
• Innervated by sympathetic nerves
• Hypothalamus is sensitive to increases in testis
  or core body temperature
• Stimulates sweat glands to provide evaporative
  cooling.
• Respiration

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Scrotum as a swamp cooler
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Importance of thermoregulation

• Waites (1961 and 1962)
• Heating device for scrotum of ram
• Scrotal exposure to 40C for 30 minutes resulted
  in the ram panting (up to 200 bpm), and lowering
  core body temperature by 1 degree
• Heating other areas of the body had little
  influence on respiratory rate

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Importance of thermoregulation
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Countercurrent exchange

• Testicular artery is highly convoluted and passed
  through the spermatic cord and surrounds the
  testes (ventromedial)
• Testicular veins are in close proximity to the
  tortuous testicular artery in spermatic cord
• Pampiniform plexus is the spermatic venous
  network which has lots of finger-like wrappings
  surrounding the spermatic artery. This allows for
  countercurrent heat exchange of veins with the
  testicular artery

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Countercurrent exchange
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Thermoregulation

• Tunica dartos smooth muscle in the scrotum
• Capable of sustained contraction, elevating
  testes in cold environmental temperatures
• Cremaster muscle is continuous with internal
  abdominal oblique muscle
• Capable of short-term contraction
• Short term elevation of testicles during fear or
  excitement
• Contraction and relaxation acts as a pump on the
  pampiniform plexus

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Thermoregulation

• Men and underwear.
• Varicoeles
• Inguinal lipomas

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Thermoregulation and testicular descent

• Testicular descent allow testicles to be kept at
  lower than core body temperature, essential for
  normal spermatogenesis
• Core body temperature is lethal for germ cells
• But there are always exceptions

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Exceptions.

• Approximately 1500 species of mammals are
  non-scrotal
• Most of these still have a trans-abdominal
  migration phase
• Why is spermatogenesis still successful?
• Some have testicles in a cooler position
• Eg tapir has subcutaneous testicles
• Some have specialized cooling systems
• E.g dolphin and vascular counter-current heat
  exchanger (dorsal fin and tail flukes)
• Some have a low core body temperature
• Eg hedgehog
• Some we just dont know

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Questions!
If you would like copies of our slides, or a list
of our references we would be happy to share!
Please email rebecca.bott_at_colostate.edu.
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Role of Androgens

• Androgens may act by regulating calcitonin gene
  related peptide (CGRP).
• CGPR localized in the genitofemoral nerve.
• Potential neurotransmitter dictating growth of
  the tip of the gubernaculum and directed
  migration of the gubernaculum into the scrotum
• Role of key factors is still debatable!

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