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Hormones

, Volume 14, Issue 4, pp 515–530 | Cite as

Testicular Descent

  • Charalampos Mamoulakis
  • Spyridon Antypas
  • Frank Sofras
  • Atsushi Takenaka
  • Nikolaos Sofikitis
Review
  • 16 Downloads

Key words

Cryptorchidism Human Mammal Testis Undescended testis 

References

  1. 1.
    Hutson JM, Balic A, Nation T, Southwell B, 2010 Cryptorchidism. Semin Pediatr Surg 19: 215–224.PubMedCrossRefGoogle Scholar
  2. 2.
    Toppari J, Kaleva M, 1999 Maldescendus testis. Horm Res 6: 261–291.Google Scholar
  3. 3.
    Bay K, Main KM, Toppari J, Skakkebæk NE, 2011 Testicular descent: INSL3, testosterone, genes and the intrauterine milieu. Nat Rev Urol 8: 187–196.PubMedCrossRefGoogle Scholar
  4. 4.
    Massart F, Saggese G, 2009 Sex steroidal targets & genetic susceptibility to idiopathic cryptorchidism. Pediatr Endocrinol Rev 6: 481–490.PubMedGoogle Scholar
  5. 5.
    Jensen MS, Toft G, Thulstrup AM, et al, 2010 Cryptorchidism concordance in monozygotic and dizygotic twin brothers, full brothers, and half-brothers. Fertil Steril 93: 124–129.PubMedCrossRefGoogle Scholar
  6. 6.
    Mamoulakis C, Sofikitis N, Tsounapi P, et al, 2013 The (TAAAA)(n) polymorphism of sex hormone-binding globulin gene is not associated with testicular maldescent. Andrologia 45: 40–45.PubMedCrossRefGoogle Scholar
  7. 7.
    Mamoulakis C, Georgiou I, Dimitriadis F, et al, 2013 Screening for Y chromosome microdeletions in childhood: lack of evidence for a direct association with testicular maldescent. Andrologia 45: 409–416.PubMedCrossRefGoogle Scholar
  8. 8.
    Mamoulakis C, Georgiou I, Dimitriadis F, et al, 2014 Genetic analysis of the human Insulin-like 3 gene: absence of mutations in a Greek paediatric cohort with testicular maldescent. Andrologia 46: 986–996.PubMedCrossRefGoogle Scholar
  9. 9.
    Hutson JM, Beasley SW 1992 Descent of the Testis. Edward Arnold, London.Google Scholar
  10. 10.
    Carrick FN, Setchell BP 1977 The evolution of the scrotum. In: Calaby JH and Tyndale-Biscoe T (eds) Reproduction and evolution. Australian Academy of Science, Camberra; pp, 165–170.Google Scholar
  11. 11.
    Harrison RM, Lewis RW 1986 The male reproductive tract and its fluids. In: Dukelow WR, Ervin J (eds) Comparative Primate Biology. Alan R Liss, New York; pp, 101–148.Google Scholar
  12. 12.
    Kinzey WG 1971 Male reproductive system and spermatogenesis. In: Hafez ESE, Springfield IL, Charles C (eds), Comparative Reproduction of Nonhuman Primates. McGraw-Hill Company of Canada, Scarborough, Ontario; pp, 85–114.Google Scholar
  13. 13.
    Moore KL, Persaud TV 1993 Clinically oriented Embryology. WB Saunders Co, Philadelphia.Google Scholar
  14. 14.
    Moore CR, 1926 The biology of the mammalian testis and scrotum. Q Rev Biol 1: 4–50.CrossRefGoogle Scholar
  15. 15.
    Short RV, 1997 The testis: the witness of the mating system, the site of mutation and the engine of desire. Acta Paediatr Suppl 422: 3–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Portman A 1952 Animal forms and Patterns. Schocken, New York.Google Scholar
  17. 17.
    Bedford JM, 1978 Anatomical evidence for the epididymis as the prime mover in the evolution of the scrotum. Am JAnat 152: 483–507.Google Scholar
  18. 18.
    Freeman S, 1990 The evolution of the scrotum: a new hypothesis. J Theor Biol 145: 429–445.PubMedCrossRefGoogle Scholar
  19. 19.
    Setchell BP, 1998 The Parkes Lecture. Heat and the testis. J Reprod Fertil 114: 179–194.PubMedCrossRefGoogle Scholar
  20. 20.
    Cowles RB, 1965 Hyperthermia, aspermia, mutation rates and evolution. Q Rev Biol 40: 728 341–367.CrossRefGoogle Scholar
  21. 21.
    VanDemark NL, Free MJ 1970 Temperature effects. In: Johnson AD, Gomes WR, VanDemark NL (eds), The Testis. Academic Press, New York; pp, 233–312.Google Scholar
  22. 22.
    Waites GM 1970 Temperature regulation and the testis. In: Johnson AD, Gomes WR, VanDemark NL (eds) The Testis. Academic Press, New York; pp, 241–279.Google Scholar
  23. 23.
    Blix AS, Fay FH, Ronald K, 1983 On testicular cooling in phocid seals. Polar Res 1: 231–233.CrossRefGoogle Scholar
  24. 24.
    Pabst DA, Rommel SA, McLellan WA, Williams TM, Rowles TK, 1995 Thermoregulation of the intra-abdominal testes of the bottlenose dolphin (Tursiops truncatus) during exercise. J Exp Biol 198: 221–226.PubMedGoogle Scholar
  25. 25.
    Macdonald D 1984 The encyclopedia of mammals. Unwin Hynam, London, UK.Google Scholar
  26. 26.
    Hanks J 1977 Comparative aspects of reproduction in the male hyrax and elephant. In Calaby JG, Tyndale-Biscoe HD (eds) Reproduction and evolution. Australian Academy of Sience, Cambera, Australia, pp, 155–164.Google Scholar
  27. 27.
    Shimmin LC, Chang BH and Li WH, 1993 Male-driven evolution of DNA sequences. Nature 362: 745–747.PubMedCrossRefGoogle Scholar
  28. 28.
    Shimmin LC, Chang BH, Li WH, 1994 Contrasting rates of nucleotide substitution in the X-linked and Y-linked zinc finger genes. J Mol Evol 39: 569–578.PubMedCrossRefGoogle Scholar
  29. 29.
    Ehrenberg L, Ehrenstein GV, Hedgran A, 1957 Gonadal temperatures and spontaneous mutation rates in man. Nature 180: 1433–1434.PubMedCrossRefGoogle Scholar
  30. 30.
    Wolfson A, 1954 Sperm storage at lower-than-body temperature outside the body cavity of some passerine birds. Science 120: 68–71.PubMedCrossRefGoogle Scholar
  31. 31.
    Woodal PF, 1995 The male reproductive system and the phylogeny of elephant-shrews. Mammal Rev 25: 87–93.CrossRefGoogle Scholar
  32. 32.
    Waites GM, Sethell BP 1969 Some physiological aspects of the function of the testis. In Meckerns KW (ed), The gonads. Appleton-Century-Crofts, New York;, pp, 649–714.Google Scholar
  33. 33.
    Eckert R, Randall D 1983 Animal physiology. Freeman, New York.Google Scholar
  34. 34.
    Ginsberg JR, Huck UW, 1989 Sperm competition in mammals. Trends Ecol Evol 4: 74–79.PubMedCrossRefGoogle Scholar
  35. 35.
    Hunter J 1786 A description of the situation of the testis in the foetus, with its descent into the scrotum. In Observations on certain parts of the animal oeconomy. London, 13 Castle St, pp, 1–26.Google Scholar
  36. 36.
    Williams MP, Hutson JM, 1991 The history of ideas about testicular descent. Pediatr Surg Int 6: 180–184.Google Scholar
  37. 37.
    Cleland J 1856 The mechanism of the gubernaculum testis, with an introductory sketch of the development of the testes, and an appendix on the purpose of their descent from the abdomen. Edinburgh, Maclachan and Stewart.Google Scholar
  38. 38.
    Gier HT, Marion GB, 1969 Development of mammalian testes and genital ducts. Biol Reprod 1(Suppl): 1–23.CrossRefGoogle Scholar
  39. 39.
    Hutson JM, 1985 A biphasic model for the hormonal control of testicular descent. Lancet 2: 419–421.PubMedCrossRefGoogle Scholar
  40. 40.
    Backhouse KM, 1982. Embryology of testicular descent and maldescent. Urol Clin North Am 9: 315–325.PubMedGoogle Scholar
  41. 41.
    Heyns CF, 1987 The gubernaculum during testicular descent in the human fetus. J Anat 153: 93–112.PubMedPubMedCentralGoogle Scholar
  42. 42.
    Hadziselimovic F, Herzog B, Kruslin E, 1979 Morphological background of estrogen-induced cryptorchidism in the mouse. Pediatr Adolesc Endocrinol 6: 79–87.Google Scholar
  43. 43.
    Hutson JM, Hasthorpe S, Heyns CF, 1997 Anatomical and functional aspects of testicular descent and cryptorchidism. Endocr Rev 18: 259–280.PubMedGoogle Scholar
  44. 44.
    Wensing CJ, 1973 Testicular descent in some domestic mammals 2. The nature of the gubernacular change during the process of testicular descent in the pig. Proc K Ned Akad Wet C 76: 190–195.Google Scholar
  45. 45.
    Hadziselimovic F, Herzog B, Kruslin E, 1980 Estrogen induced cryptorchidism in animals. Clin Androl 3: 166–174.Google Scholar
  46. 46.
    van der Schoot P, 1993 Doubts about the ‘first phase of testis descent’ in the rat as a valid concept. Anat Embryol (Berl) 187: 203–208.CrossRefGoogle Scholar
  47. 47.
    Clarnette TD, Hutson JM, Beasley SW, 1996 Factors affecting the development of the processus vaginalis in the rat. J Urol 156: 1463–1466.PubMedCrossRefGoogle Scholar
  48. 48.
    Wensing CJ, Colenbrander B, van Straaten HW 1980 Normal and abnormal testicular descent in some mammals. In ESE Hafez (ed) Clinics in Andrology: Descended and Cryptorchid Testis. Martinus Nijhoff, The Hague; pp, 125–137.CrossRefGoogle Scholar
  49. 49.
    Tayakkanonta K, 1963 The gubernaculum testis and its nerve supply. Aust NZ J Surg 33: 61–67.CrossRefGoogle Scholar
  50. 50.
    Heyns CF, 1982 The gubernaculum during testicular descent and maldescent. Urol Clin N Am 9: 315–325.Google Scholar
  51. 51.
    Elder JS, Isaacs JT, Walsh PC, 1982 Androgenic sensitivity of the gubernaculum testis: evidence for hormonal/mechanical interactions in testicular descent. J Urol 127: 170–176.PubMedCrossRefGoogle Scholar
  52. 52.
    Frey HL, Peng S, Rajfer J, 1983 Synergy of abdominal pressure and androgens in testicular descent. Biol Reprod 29: 1233–1239.PubMedCrossRefGoogle Scholar
  53. 53.
    Hutson JM, Terada M, Zhou B, Williams MP, 1995 Normal testicular descent and the aetiology of cryptorchidism. Adv Anat Embryol Cell Biol 132: 1–56.Google Scholar
  54. 54.
    Kersten W, Molenaar GJ, Emmen JM, van der Schoot P, 1996 Bilateral cryptorchidism in a dog with persistent cranial testis suspensory ligaments and inverted gubernacula: report of a case with implications for understanding normal and aberrant testis descent. J Anat 189: 171–176.PubMedPubMedCentralGoogle Scholar
  55. 55.
    van der Schoot P, Emmen JM, 1996 Development, structure and function of the cranial suspensory ligaments of the mammalian gonads in a cross-species perspective; their possible role in effecting disturbed testicular descent. Hum Reprod Update 2: 399–418.PubMedCrossRefGoogle Scholar
  56. 56.
    Barthold JS, Mahler HR, Newton BW, 1994 Lack of feminization of the cremaster nucleus in cryptorchid androgen insensitive rats. J Urol 152: 2280–2286.PubMedCrossRefGoogle Scholar
  57. 57.
    van der Schoot P, Elger W, 1992 Androgen-induced prevention of the outgrowth of cranial gonadal suspensory ligaments in fetal rats. J Androl 13: 534–542.PubMedGoogle Scholar
  58. 58.
    Clarnette TD, Sugita Y, Hutson JM, 1997 Genital anomalies in human and animal models reveal the mechanisms and hormones governing testicular descent. Br J Urol 79: 99–112.PubMedCrossRefGoogle Scholar
  59. 59.
    Hutson JM, 1986 Testicular feminization: a model for testicular descent in mice and men. J Pediatr Surg 21: 195–198.PubMedCrossRefGoogle Scholar
  60. 60.
    Emmen JM, McLuskey A, Grootegoed JA, Brinkmann AO, 1998 Androgen action during male sex differentiation includes suppression of cranial suspensory ligament development. Hum Reprod 13: 1272–1280.PubMedCrossRefGoogle Scholar
  61. 61.
    Scott JE, 1987 The Hutson hypothesis. A clinical study. Br J Urol 60: 74–76.PubMedCrossRefGoogle Scholar
  62. 62.
    Husmann DA, Levy JB, 1995 Current concepts in the pathophysiology of testicular undescent. Urology 46: 267–276.PubMedCrossRefGoogle Scholar
  63. 63.
    Backhouse KM, Butler H, 1960 The gubernaculum testis of the pig (sus scropha). J Anat 94: 107–121.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Heyns CF, Human HJ, DeKlerk DP, 1986 Hyperplasia and hypertrophy of the gubernaculum during testicular descent in the fetus. J Urol 135: 1043–1047.PubMedCrossRefGoogle Scholar
  65. 65.
    Heyns CF, Human HJ, Werely CJ, De Klerk DP, 1990 The glycosaminoglycans of the gubernaculum during testicular descent in the fetus. J Urol 143: 612–617.PubMedCrossRefGoogle Scholar
  66. 66.
    Lillie FR, 1917 The freemartin: a study of the action of sex hormones in the foetal life of a cattle. J Exp Zool 23: 371–452.CrossRefGoogle Scholar
  67. 67.
    Van der Schoot P, Vigier B, Prepin J, Perchellet JP, Gittenberger de Groot A, 1995 Development of the gubernaculum and processus vaginalis in freemartinism: further evidence in support of a specific fetal testis hormone governing male-specific gubernacular development. Anat Rec 241: 211–224.PubMedCrossRefGoogle Scholar
  68. 68.
    van der Schoot P, 1993 Foetal testes control the prenatal growth and differentiation of the gubernacular cones in rabbits-a tribute to the late Professor Alfred Jost. Development 118: 1327–1334.PubMedGoogle Scholar
  69. 69.
    Habenicht UF, Neumann F, 1983 Hormonal regulation of testicular descent. Adv Anat Embryol Cell Biol 81: 1–54.PubMedCrossRefGoogle Scholar
  70. 70.
    Bentvelsen FM, George FW, 1993 The fetal rat gubernaculum contains higher levels of androgen receptor than does the postnatal gubernaculum. J Urol 150: 1564–1566.PubMedCrossRefGoogle Scholar
  71. 71.
    Husmann DA, McPhaul MJ, 1991 Localization of the androgen receptor in the developing rat gubernaculum. Endocrinology 128: 383–387.PubMedCrossRefGoogle Scholar
  72. 72.
    Heyns CF, Pape VC, 1991 Presence of a low capacity androgen receptor in the gubernaculum of the pig fetus. J Urol 145: 161–167.PubMedCrossRefGoogle Scholar
  73. 73.
    Ahmed SF, Cheng A, Dovey L, et al, 2000 Phenotypic features, androgen receptor binding, and mutational analysis in 278 clinical cases reported as androgen insensitivity syndrome. J Clin Endocrinol Metab 85: 658–665.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Fentener van Vlissingen JM, Colenbrader B, Verbruggen A, Wensing CJ 1984 Testicular feminized males (TFM) in Nyctereutes procyonoides (Raccoon, dog). In Recent Progress in Cellular Endocrinology of the Testis. INSERM Symposium, Elsevier, Amsterdam; pp, 335–340.Google Scholar
  75. 75.
    Wensing CJ, Colenbrander B, Bosma AA, 1975 Testicular feminisation syndrome and gubernacular development in a pig. Proc K Ned Akad Wet C 78: 402–405.Google Scholar
  76. 76.
    Elger W, Richter J, Korte R 1977 Failure to detect androgen dependence of the descensus testiculorum in foetal rabbits, mice and monkeys. In: Bierich JR, Rager K, Ranke MB (eds) Maldescensus testis. Urban & Schwarzenberg, Baltimore; pp, 187–191.Google Scholar
  77. 77.
    Hutson JM, Beasley SW, 1988 Embryological controversies in testicular descent. Semin Urol 6: 68–73.PubMedGoogle Scholar
  78. 78.
    Wensing CJ, 1973 Testicular descent in some domestic mammals. 3. Search for the factors that regulate the gubernacular reaction. Proc K Ned Akad Wet C 76: 196–202.PubMedGoogle Scholar
  79. 79.
    Shono T, Ramm Anderson S, Goh DW, Hutson JM, 1994 The effect of flutamide on testicular descent in rats examined by scanning electron microscopy. J Pediatr Surg 29: 839–844.PubMedCrossRefGoogle Scholar
  80. 80.
    Baumans V, Dijkstra G, Wensing CJ, 1982 The effect of orchidectomy on gubernacular outgrowth and regression in the dog. Int J Androl 5: 387–400.PubMedCrossRefGoogle Scholar
  81. 81.
    Baumans V, Dijkstra G, Wensing CJ, 1983 The role of a non-androgenic testicular factor in the process of testicular descent in the dog. Int J Androl 6: 541–552.PubMedCrossRefGoogle Scholar
  82. 82.
    Emmen JM, McLuskey A, Adham IM, Engel W, Grootegoed JA, Brinkmann AO, 2000 Hormonal control of gubernaculum development during testis descent: gubernaculum outgrowth in vitro requires both insulin-like factor and androgen. Endocrinology 141: 4720–4727.PubMedCrossRefGoogle Scholar
  83. 83.
    Fentener van Vlissingen JM, van Zoelen EJ, Ursem PJ, Wensing CJ, 1988 In vitro model of the first phase of testicular descent: identification of a low molecular weight factor from fetal testis involved in proliferation of gubernaculum testis cells and distinct from specified polypeptide growth factors and fetal gonadal hormones. Endocrinology 123: 2868–2877.PubMedCrossRefGoogle Scholar
  84. 84.
    Kubota Y, Temelcos C, Bathgate RA, et al, 2002 The role of insulin 3, testosterone, Mullerian inhibiting substance and relaxin in rat gubernacular growth. Mol Hum Reprod 8: 900–905.PubMedCrossRefGoogle Scholar
  85. 85.
    Visser JH, Heyns CF, 1995 Proliferation of gubernaculum cells induced by a substance of low molecular mass obtained from fetal pig testes. J Urol 153: 516–520.PubMedCrossRefGoogle Scholar
  86. 86.
    Hadziselimovic F 1983 Embryology of Testicular Descent and Maldescent. In: Hadziselimovic F (ed) Cryptorchidism. Management and Implications. Springer-Verlag, Berlin; pp, 11–34.CrossRefGoogle Scholar
  87. 87.
    Raynaud A, 1958 Inhibition, sous l’effect d’une hormone oestrogène, du développement du gubernaculum du fœtus mâle de souris. CR Acad Sc Paris 246: 176–179.Google Scholar
  88. 88.
    Shono T, Hutson JM, Watts L, et al, 1996 Scanning electron microscopy shows inhibited gubernacular development in relation to undescended testes in oestrogen-treated mice. Int J Androl 19: 263–270.PubMedCrossRefGoogle Scholar
  89. 89.
    Hutson JM, 1987 Exogenous oestrogens prevent transabdominal testicular descent in mice with complete androgen resistance (testicular feminization). Pediatr Surg Int 2: 242–246.Google Scholar
  90. 90.
    Hutson JM, Watts LM, 1990 Both gonadotropin and testosterone fail to reverse estrogen-induced cryptorchidism in fetal mice: further evidence for nonandrogenic control of testicular descent in the fetus. Pediatr Surg Int 5: 13–18.CrossRefGoogle Scholar
  91. 91.
    Hutson JM, Donahoe PK, 1986 The hormonal control of testicular descent. Endocr Rev 7: 270–283.PubMedCrossRefGoogle Scholar
  92. 92.
    Hutson JM, Chow DW, Ng WD, 1987 Persistent Mullerian duct syndrome with transverse testicular ectopia. An experiment of the nature with clues for understanding testicular descent. Pediatr Surg Int 2: 191–194.Google Scholar
  93. 93.
    Hutson JM, Davidson PM, Reece LA, Baker M, Zhou B, 1994 Failure of gubernacular development in the persistent Müllerian duct syndrome allows herniation of the testes. Pediatr Surg Int 9: 544–546.Google Scholar
  94. 94.
    Tran D, Picard JY, Vigier B, Berger R, Josso N, 1986 Persistence of mullerian ducts in male rabbits passively immunized against bovine anti-mullerian hormone during fetal life. Dev Biol 116: 160–167.PubMedCrossRefGoogle Scholar
  95. 95.
    Bartlett JE, Lee SM, Mishina Y, et al, 2002 Gubernacular development in Mullerian inhibiting substance receptor-deficient mice. BJU Int 89; 113–118.PubMedCrossRefGoogle Scholar
  96. 96.
    Behringer RR, Finegold MJ, Cate RL, 1994 Mullerian-inhibiting substance function during mammalian sexual development. Cell 79: 415–425.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Mishina Y, Rey R, Finegold MJ, et al, 1996 Genetic analysis of the Mullerian-inhibiting substance signal transduction pathway in mammalian sexual differentiation. Genes Dev 10: 2577–2587.PubMedCrossRefGoogle Scholar
  98. 98.
    Catlin EA, MacLaughlin DT, Donahoe PK, 1993 Mullerian inhibiting substance: new perspectives and future directions. Microsc Res Tech 25: 121–133.PubMedCrossRefGoogle Scholar
  99. 99.
    Guerrier D, Tran D, Vanderwinden JM, et al, 1989 The persistent Mullerian duct syndrome: a molecular approach. J Clin Endocrinol Metab 68: 46–52.PubMedCrossRefGoogle Scholar
  100. 100.
    Josso N, Picard JY, Imbeaud S, di Clemente N, Rey R, 1997 Clinical aspects and molecular genetics of the persistent mullerian duct syndrome. Clin Endocrinol (Oxf) 47: 137–144.CrossRefGoogle Scholar
  101. 101.
    Nef S, Parada LF, 1999 Cryptorchidism in mice mutant for Insl3. Nat Genet 22: 295–299.PubMedCrossRefGoogle Scholar
  102. 102.
    Zimmermann S, Steding G, Emmen JM, et al, 1999 Targeted disruption of the Insl3 gene causes bilateral cryptorchidism. Mol Endocrinol 13: 681–691.PubMedCrossRefGoogle Scholar
  103. 103.
    Adham IM, Burkhardt E, Benahmed M, Engel W, 1993 Cloning of a cDNA for a novel insulin-like peptide of the testicular Leydig cells. J Biol Chem 268: 26668–26672.PubMedGoogle Scholar
  104. 104.
    Zimmermann S, Schottler P, Engel W, Adham IM, 1997 Mouse Leydig insulin-like (Ley I-L) gene: structure and expression during testis and ovary development. Mol Reprod Dev 47: 30–38.PubMedCrossRefGoogle Scholar
  105. 105.
    Ivell R, Balvers M, Domagalski R, Ungefroren H, Hunt N, Schulze W, 1997 Relaxin-like factor: a highly specific and constitutive new marker for Leydig cells in the human testis. Mol Hum Reprod 3: 459–466.PubMedCrossRefGoogle Scholar
  106. 106.
    Adham IM, Emmen JM, Engel W, 2000 The role of the testicular factor INSL3 in establishing the gonadal position. Mol Cell Endocrinol 160: 11–16.PubMedCrossRefGoogle Scholar
  107. 107.
    Irving Rodgers HF, Bathgate RA, Ivell R, Domagalski R, Rodgers RJ, 2002 Dynamic changes in the expression of relaxin-like factor (INSL3), cholesterol side-chain cleavage cytochrome p450, and 3beta-hydroxysteroid dehydrogenase in bovine ovarian follicles during growth and atresia. Biol Reprod 66: 934–943.PubMedCrossRefGoogle Scholar
  108. 108.
    Kubota Y, Nef S, Farmer PJ, Temelcos C, Parada LF, Hutson JM, 2001 Leydig insulin-like hormone, gubernacular development and testicular descent. J Urol 165: 1673–1675.PubMedCrossRefGoogle Scholar
  109. 109.
    Nguyen MT, Showalter PR, Timmons CF, Nef S, Parada LF, Baker LA, 2002 Effects of orchiopexy on congenitally cryptorchid insulin-3 knockout mice. J Urol 168: 1779–1783.PubMedCrossRefGoogle Scholar
  110. 110.
    Adham IM, Steding G, Thamm T, et al, 2002 The overexpression of the insl3 in female mice causes descent of the ovaries. Mol Endocrinol 16: 244–252.PubMedCrossRefGoogle Scholar
  111. 111.
    Kumagai J, Hsu SY, Matsumi H, et al, 2002 INSL3/Leydig insulin-like peptide activates the LGR8 receptor important in testis descent. J Biol Chem 277: 31283–31286.PubMedCrossRefGoogle Scholar
  112. 112.
    Kawamura K, Kumagai J, Sudo S, et al, 2004 Paracrine regulation of mammalian oocyte maturation and male germ cell survival. Proc Natl Acad Sci USA 101: 7323–7328.PubMedCrossRefGoogle Scholar
  113. 113.
    Burkhardt E, Adham IM, Brosig B, Gastmann A, Mattei MG, Engel W, 1994 Structural organization of the porcine and human genes coding for a Leydig cell-specific insulin-like peptide (LEY I-L) and chromosomal localization of the human gene (INSL3). Genomics 20: 13–19.PubMedCrossRefGoogle Scholar
  114. 114.
    Donaldson KM, Tong SY, Washburn T, et al, 1996 Morphometric study of the gubernaculum in male estrogen receptor mutant mice. J Androl 17: 91–95.PubMedGoogle Scholar
  115. 115.
    Koskimies P, Virtanen H, Lindström M, et al, 2000 A common polymorphism in the human relaxin-like factor (RLF) gene: no relationship with cryptorchidism. Pediatr Res 47: 538–541.PubMedCrossRefGoogle Scholar
  116. 116.
    Krausz C, Quintana-Murci L, Fellous M, et al, 2000 Absence of mutations involving the INSL3 gene in human idiopathic cryptorchidism. Mol Hum Reprod 6: 298–302.PubMedCrossRefGoogle Scholar
  117. 117.
    Tomboc M, Lee PA, Mitwally MF, et al, 2000 Insulin-like 3/relaxin-like factor gene mutations are associated with cryptorchidism. J Clin Endocrinol Metab 85: 4013–4018.PubMedGoogle Scholar
  118. 118.
    Lim HN, Raipert-de Meyts E, Skakkebaek NE, et al, 2001 Genetic analysis of the INSL3 gene in patients with maldescent of the testis. Eur J Endocrinol 144: 129–137.PubMedCrossRefGoogle Scholar
  119. 119.
    Ferlin A, Arredi B, Foresta C, 2006 Genetic causes of male infertility. Reprod Toxicol 22: 133–141.PubMedCrossRefGoogle Scholar
  120. 120.
    Ferlin A, Arredi B, Zuccarello D, Garolla A, Selice R, Foresta C, 2006 Paracrine and endocrine roles of insulin-like factor 3. J Endocrinol Invest 29: 657–664.PubMedCrossRefGoogle Scholar
  121. 121.
    Ferlin A, Bogatcheva NV, Gianesello L, et al, 2006 Insulin-like factor 3 gene mutations in testicular dysgenesis syndrome: clinical and functional characterization. Mol Hum Reprod 12: 401–406.PubMedCrossRefGoogle Scholar
  122. 122.
    Bay K, Virtanen HE, Hartung S, et al, 2007 Insulin-like factor 3 levels in cord blood and serum from children: effects of age, postnatal hypothalamic-pituitary-gonadal axis activation, and cryptorchidism. J Clin Endocrinol Metab 92: 4020–4027.PubMedCrossRefGoogle Scholar
  123. 123.
    Foresta C, Zuccarello D, Garolla A, Ferlin A, 2008 Role of hormones, genes, and environment in human cryptorchidism. Endocr Rev 29: 560–580.PubMedCrossRefGoogle Scholar
  124. 124.
    Gorlov IP, Kamat A, Bogatcheva NV, Jones E, Lamb DJ, Truong A, et al, 2002 Mutations of the GREAT gene cause cryptorchidism. Hum Mol Genet 11: 2309–2318.PubMedCrossRefGoogle Scholar
  125. 125.
    Bogatcheva NV, Ferlin A, Feng S, et al, 2007 T222P mutation of the insulin-like 3 hormone receptor LGR8 is associated with testicular maldescent and hinders receptor expression on the cell surface membrane. Am J Physiol Endocrinol Metab 292: E138–144.PubMedCrossRefGoogle Scholar
  126. 126.
    Ars E, Lo Giacco D, Bassas L, et al, 2011 Further insights into the role of T222P variant of RXFP2 in non-syndromic cryptorchidism in two Mediterranean populations. Int J Androl 34: 333–338.PubMedCrossRefGoogle Scholar
  127. 127.
    Nuti F, Marinari E, Erdei E, et al, 2008 The leucine-rich repeat-containing G protein-coupled receptor 8 gene T222P mutation does not cause cryptorchidism. J Clin Endocrinol Metab 93: 1072–1076.PubMedCrossRefGoogle Scholar
  128. 128.
    Roh J, Virtanen H, Kumagai J, et al, 2003 Lack of LGR8 gene mutation in Finnish patients with a family history of cryptorchidism. Reprod Biomed Online 2003 7: 400–406.CrossRefGoogle Scholar
  129. 129.
    El Houate B, Rouba H, Imken L, et al, 2008 No association between T222P/LGR8 mutation and cryptorchidism in the Moroccan population. Horm Res 70: 236–239.PubMedCrossRefGoogle Scholar
  130. 130.
    Kaplan LM, Koyle MA, Kaplan GW, Farrer JH, Rajfer J, 1986 Association between abdominal wall defects and cryptorchidism. J Urol 136: 645–647.PubMedCrossRefGoogle Scholar
  131. 131.
    Koivusalo A, Taskinen S, Rintala RJ, 1998 Cryptorchidism in boys with congenital abdominal wall defects. Pediatr Surg Int 13: 143–145.PubMedCrossRefGoogle Scholar
  132. 132.
    Attah AA, Hutson JM, 1993 The role of intra-abdominal pressure in cryptorchidism. J Urol 150: 994–996.PubMedCrossRefGoogle Scholar
  133. 133.
    Fallat ME, Williams MPL, Farmer PJ, Hutson JM, 1992 Histologic evaluation of inguinoscrotal migration of the gubernaculum in rodents during testicular descent and its relationship to the genitofemoral nerve. Pediatr Surg Int 7: 265–270.Google Scholar
  134. 134.
    Radhakrishnan J, Donahoe PK 1981 The Gubernaculum and Testicular Descent. In: Fonkalsrud EW, Mengel W (eds) The Undescended Testis. Year Book Medical Publishers, Chicago; pp, 30–41.Google Scholar
  135. 135.
    Hrabovszky Z, Di Pilla N, Yap T, Farmer PJ, Hutson JM Carlin JB, 2002 Role of the gubernacular bulb in cremaster muscle development of the rat. Anat Rec 267: 159–165.PubMedCrossRefGoogle Scholar
  136. 136.
    Costa WS, Sampaio FJ, Favorito LA, Cardoso LE, 2002 Testicular migration: remodeling of connective tissue and muscle cells in human gubernaculum testis. J Urol 167: 2171–2176.PubMedCrossRefGoogle Scholar
  137. 137.
    Grocock CA, Charlton HM, Pike MC, 1988 Role of the fetal pituitary in cryptorchidism induced by exogenous maternal oestrogen during pregnancy in mice. J Reprod Fertil 83: 295–300.PubMedCrossRefGoogle Scholar
  138. 138.
    Goh DW, Middlesworth W, Farmer PJ, Hutson JM, 1994 Prenatal androgen blockade with flutamide inhibits masculinization of the genitofemoral nerve and testicular descent. J Pediatr Surg 29: 836–838.PubMedCrossRefGoogle Scholar
  139. 139.
    McMahon DR, Kramer SA, Husmann DA, 1995 Antiandrogen induced cryptorchidism in the pig is associated with failed gubernacular regression and epididymal malformations. J Urol 154: 553–557.PubMedCrossRefGoogle Scholar
  140. 140.
    Spencer JR, Torrado T, Sanchez RS, Vaughan ED, Imperato McGinley J, 1991 Effects of flutamide and finasteride on rat testicular descent. Endocrinology 129: 741–748.PubMedCrossRefGoogle Scholar
  141. 141.
    Husmann DA, McPhaul MJ, 1991 Time-specific androgen blockade with flutamide inhibits testicular descent in the rat. Endocrinology 129: 1409–1416.PubMedCrossRefGoogle Scholar
  142. 142.
    Husmann DA, McPhaul MJ, 1992 Reversal of flutamide-induced cryptorchidism by prenatal time-specific androgens. Endocrinology 131: 1711–1715.PubMedCrossRefGoogle Scholar
  143. 143.
    Johansen TE, Klein H, 1993 Evidence of androgen receptivity in the pathway of testicular descent in humans. A postnatal study. Eur Urol 23: 466–468.PubMedCrossRefGoogle Scholar
  144. 144.
    Oprins AC, Fentener van Vlissingen JM, Blankenstein MA, 1988 Testicular descent: androgen receptors in cultured porcine gubernaculum cells. J Steroid Biochem 31: 387–391.PubMedCrossRefGoogle Scholar
  145. 145.
    Heyns CF, Pape VC, DeKlerk DP, 1988 Demonstration of a cytosolic androgen receptor in the gubernaculum of the pig fetus. J Urol 139: 236.Google Scholar
  146. 146.
    Heyns CF, Tate R, Sargent NS, Habib FK, Chisholm GD, 1993 Absence of 5 alpha-reductase activity in the gubernaculum during descent of the fetal pig testis. J Urol 150: 510–513.PubMedCrossRefGoogle Scholar
  147. 147.
    George FW, Peterson KG, 1988 Partial characterization of the androgen receptor of the newborn rat gubernaculum. Biol Reprod 39: 536–539.PubMedCrossRefGoogle Scholar
  148. 148.
    Hutson JM, Beasley SW, 1987 The mechanisms of testicular descent. Aust Paediatr J 23: 215–216.PubMedGoogle Scholar
  149. 149.
    Lewis LG, 1948. Cryptorchidism. J Urol 60: 345–346.PubMedCrossRefGoogle Scholar
  150. 150.
    Cain MP, Kramer SA, Tindall DJ, Husmann DA, 1994 Expression of androgen receptor protein within the lumbar spinal cord during ontologic development and following antiandrogen induced cryptorchidism. J Urol 152: 766–769.PubMedCrossRefGoogle Scholar
  151. 151.
    Larkins SL, Hutson JM, 1991 Fluorescent anterograde labelling of the genitofemoral nerve shows that it supplies the scrotal region before migration of the gubernaculum. Pediatr Surg Int 6: 167–171.Google Scholar
  152. 152.
    Beasley SW, Hutson JM, 1988 The role of the gubernaculum in testicular descent. J Urol 140: 1191–1193.PubMedCrossRefGoogle Scholar
  153. 153.
    Bergh A, Heiander HF, Wahlquist L, 1978 Studies on factors governing testicular descent in the rat-particularly the role of gubernaculum testis. Int J Androl 1: 342–356.CrossRefGoogle Scholar
  154. 154.
    Hutson JM, Beasley SW, Bryan AD, 1988 Cryptorchidism in spina bifida and spinal cord transection: a clue to the mechanism of transinguinal descent of the testis. J Pediatr Surg 23: 275–277.PubMedCrossRefGoogle Scholar
  155. 155.
    Park WH, Hutson JM, 1991 The gubernaculum shows rhythmic contractility and active movement during testicular descent. J Pediatr Surg 26: 615–617.PubMedCrossRefGoogle Scholar
  156. 156.
    Momose Y, Griffiths AL, Hutson JM, 1992 Testicular descent. III. The neonatal mouse gubernaculum shows rhythmic contraction in organ culture in response to calcitonin gene-related peptide. Endocrinology 131: 2881–2884.PubMedCrossRefGoogle Scholar
  157. 157.
    Beasley SW, Hutson JM, 1987 Effect of division of the genitofemoral nerve on testicular descent in the rat. Aust NZJ Surg 57: 49–51.CrossRefGoogle Scholar
  158. 158.
    Zuccarello D, Morini E, Douzgou S, et al, 2004 Preliminary data suggest that mutations in the CgRP pathway are not involved in human sporadic cryptorchidism. J Endocrinol Invest 27: 760–764.PubMedCrossRefGoogle Scholar
  159. 159.
    Barthold JS, Mahler HR, Sziszak TJ, Newton BW, 1996 Lack of feminization of the cremaster nucleus by prenatal flutamide administration in the rat and pig. J Urol 156:767–771.PubMedCrossRefGoogle Scholar
  160. 160.
    Goh DW, Farmer PJ, Hutson JM, 1994 Absence of normal sexual dimorphism of the genitofemoral nerve spinal nucleus in the mutant cryptorchid (TS) rat. J Reprod Fertil 102: 195–199.PubMedCrossRefGoogle Scholar
  161. 161.
    Larkins SL, Williams MPL, Hutson JM, 1991 Localization of calcitonin gene-related peptide within the spinal nucleus of the genitofemoral nerve. Pediatr Surg Int 6: 176–179.Google Scholar
  162. 162.
    Newton BW, Unger J, Hamill RW, 1990 Calcitonin gene-related peptide and somatostatin immunoreactivities in the rat lumbar spinal cord: sexually dimorphic aspects. Neuroscience 37: 471–489.PubMedCrossRefGoogle Scholar
  163. 163.
    Schwindt B, Farmer PJ, Watts LM, Hrabovszky Z, Hutson JM, 1999 Localization of calcitonin gene-related peptide within the genitofemoral nerve in immature rats. J Pediatr Surg 34: 986–991.PubMedCrossRefGoogle Scholar
  164. 164.
    Hrabovszky Z, Farmer PJ, Hutson JM, 2000 Does the sensory nucleus of the genitofemoral nerve have a role in testicular descent? J Pediatr Surg 35: 96–100.PubMedCrossRefGoogle Scholar
  165. 165.
    Hrabovszky Z, Farmer PJ, Hutson JM, 2001 Undescended testis is accompanied by calcitonin gene related peptide accumulation within the sensory nucleus of the genitofemoral nerve in trans-scrotal rats. J Urol 165: 1015–1018.PubMedCrossRefGoogle Scholar
  166. 166.
    Hutson JM, Southwell BR, Li R, et al 2013, The regulation of testicular descent and the effects of cryptorchidism. Endocr Rev 34: 725–752.PubMedCrossRefGoogle Scholar
  167. 167.
    Kaftanovskaya EM, Feng S, Huang Z, et al, 2011 Suppression of insulin-like 3 receptor reveals the role of β-catenin and Notch signaling in gubernaculum development. Mol Endocrinol 25: 170–183.PubMedCrossRefGoogle Scholar
  168. 168.
    Yuan FP, Li X, Lin J, et al, 2010 The role of RXFP2 in mediating androgen-induced inguinoscrotal testis descent in LH receptor knockout mice. Reproduction 139: 759–769.PubMedPubMedCentralCrossRefGoogle Scholar
  169. 169.
    Laguë E, Tremblay JJ 2008 Antagonistic effects of testosterone and the endocrine disruptor mono-(2-ethylhexyl) phthalate on INSL3 transcription in Leydig cells. Endocrinology 149: 4688–4694.PubMedCrossRefGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2015

Authors and Affiliations

  • Charalampos Mamoulakis
    • 1
  • Spyridon Antypas
    • 2
  • Frank Sofras
    • 1
  • Atsushi Takenaka
    • 3
  • Nikolaos Sofikitis
    • 4
  1. 1.Department of Urology, University General Hospital of HeraklionUniversity of Crete Medical SchoolHeraklion, CreteGreece
  2. 2.First Pediatric Surgery ClinicAghia Sophia Children’s HospitalAthensGreece
  3. 3.Department of UrologyTottori University School of MedicineYonagoJapan
  4. 4.Laboratory of Molecular Urology and Genetics of Human Reproduction, Department of UrologyIoannina University School of MedicineIoanninaGreece

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