Embryology of the Female Genital Tract and Disorders of Abnormal Sexual Development

  • Stanley J. Robboy
  • Peter F. Bernhardt
  • Tim Parmley


An appreciation of the embryologie development of the genital tract provides the background for understanding many pathologic conditions encountered in the female. Among these are disorders of abnormal sexual development, which are closely linked with abnormalities occurring in early embryological development.


Sertoli Cell Leydig Cell Seminiferous Tubule Turner Syndrome External Genitalia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Abbas NE, Toublanc JE, Boucekkine C, Toublanc M, Af-fara NA, Job JC, Fellous M (1990) A possible common origin of “Y-negative” human XX males and XX true hermaphrodites. Hum Geneti 84: 356–360Google Scholar
  2. 2.
    Cantrell MA, Bicknell JN, Pagon RA, Page DC, Walker DC, Saal HM, Zinn AB, Disteche CM (1989) Molecular analysis of 46, XY females and regional assignment of a new Y chromosome specific probe. Human Genetics. 83: 88–92PubMedCrossRefGoogle Scholar
  3. 3.
    de la Chapelle A, Hastbacka J, Korhonen T, Maenpaa J (1990) The etiology of XX sex reversal. Reprod Nutr Devel Suppl 1: 39s–49sCrossRefGoogle Scholar
  4. 4.
    Coulam CB (1979) Testicular regression syndrome. Obstet Gynecol 53: 44–49PubMedGoogle Scholar
  5. 5.
    Cunha GR, Alarid ET, Turner T, Donjacour AA, Boutin EL, Foster BA (1992) Normal and abnormal development of the male genital tract. Role of androgens, mesenchymal-epithelial, and growth factors. J Andrai 13: 465–475Google Scholar
  6. 6.
    Cunha GR, Young P (1992) Role of stroma in oestrogen-induced epithelial proliferation. Epithel Cell Biol 1: 18–31Google Scholar
  7. 7.
    Dean HJ, Shackleton CHL, Winter JSD (1984) Diagnosis and natural history of 17-hydroxylase deficiency in a newborn male. J Clin Endocrinol Metabol 59: 513–520CrossRefGoogle Scholar
  8. 8.
    Disteche CM, Casanova M, Saal H, Friedman C, Sybert V, Graham J, Thuline H, Page DC, Fellous M (1986) Small deletions of the short arm of the Y chromosome in 46, XY females. Proc Nati Acad Sci 83: 7841–7844CrossRefGoogle Scholar
  9. 9.
    Donahoe PK (1992) Mullerian inhibiting substance in reproduction and cancer. Mol Reprod Dev 32: 168–172PubMedCrossRefGoogle Scholar
  10. 10.
    Eicher EM, Beamer WG, Washburn LL, Whitten WK (1980) A cytogenetic investigation of inherited true hermaphroditism in BALB/cWt mice. Cytogenet Cell Genet 28: 104–115PubMedCrossRefGoogle Scholar
  11. 11.
    Fernandes ET, Hollabaugh RS, Young JA, Wilroy SR, Schriock EA (1990) Persistent mullerian duct syndrome. Urology 36: 516–518PubMedCrossRefGoogle Scholar
  12. 12.
    Fil C, Scully RE (1990) Case records of the Massachusetts General Hospital, case 13-1990. Eng J Med 322: 917–925CrossRefGoogle Scholar
  13. 13.
    Furguson-Smith MA, Cooke A, Affara NA, Boyd E, Tomlie JL (1990) Genotype-phenotype correlations in XX males and their bearing on current theories of sex determination. Hum Genet 84: 198–202Google Scholar
  14. 14.
    Fuse H, Satomi S, Kazama T, Katayama T, Nagabuchi S, Tamura T, Nakahori Y, Nakagome Y (1991) DNA hybridization study using Y-specific probes in an XX-male. Andrologia 23: 237–239PubMedCrossRefGoogle Scholar
  15. 15.
    Griffin JE (1992) Androgen resistance—the clinical and molecular spectrum. N Engl J Med 326: 61–68CrossRefGoogle Scholar
  16. 16.
    Gubbay J, Collignon J, Koopman P, Capel B, Economan A, Musterberg A, Vivian N, Goodfellow PN, Lovell-Badge R (1990) A gene mapping to the sex determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature 346: 245–250PubMedCrossRefGoogle Scholar
  17. 17.
    Guerrier D, Tran D, Vanderwinden JM, Hideux S, van Outrive L, Legeai L, Bouchard M, van Vliet G, de Haet MH, Picard JY, Kahn A, Josso N (1989) The persistent müUerian duct syndrome: A molecular approach. J Clin Endocrinol Metab 68: 46–52PubMedCrossRefGoogle Scholar
  18. 18.
    Gustafson ML, Lee MM, Scully RE, Moncure AC, Hirakawa T, Goodman A, Muntz HG, Donahoe PK, Mac-Laughlin DT, Fuller AF (1992) Mullerian inhibiting substance as a marker for ovarian sex cord tumor. N Engl J Med 326: 466–471PubMedCrossRefGoogle Scholar
  19. 19.
    Hall JC, Gilchrist DM (1990) Turner syndrome and its variants. Pediat Clin North Am 37: 1421–1440Google Scholar
  20. 20.
    Harley VR, Jackson DI, Hextall PJ, Hawkins JR, Berkovitz GD, Sockanathan S, Lovell-Badge R, Goodfellow PN (1992) DNA binding activity of recombinant SRY from normal males and XY females. Science 255: 453–456PubMedCrossRefGoogle Scholar
  21. 21.
    Hudson PL, Dougas I, Donahoe PK, Cate RL, Epstein J, Pepinsky RB, MacLaughlin DT (1990) An immunoassay to detect human müllerian inhibiting substance in males and females during normal development. J Clin Endocrinol Metab 70: 16–22PubMedCrossRefGoogle Scholar
  22. 22.
    Imperato-McGinley J, Miller M, Wilson JD, Peterson RE, Schackleton C, and Gajdusek DC (1991) A cluster of male pseudohermaphrodites with 5 alpha-reductase deficiency in Papua New Guinea. Clin Endocrinol 34: 293–298CrossRefGoogle Scholar
  23. 23.
    Jager RJ, Epensperger C, Fraccaro M, Scherer G (1990) A ZFY negative 46, XX true hermaphrodite is positive for the Y pseudoautosomal boundary. Hum Genet 85: 666–668PubMedCrossRefGoogle Scholar
  24. 24.
    Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell-Badge R (1991) Male development of chromosomally female mice transgenic for Sry. Nature 351: 117–21PubMedCrossRefGoogle Scholar
  25. 25.
    Krauss CM, Turksoy RN, Atkins L, McLaughlin C, Brown LG, Page DC (1987) Familial premature ovarian failure due to an interstitial deletion of the long arm of the X chromosome. N Engl J Med 317: 125–131PubMedCrossRefGoogle Scholar
  26. 26.
    Kuroda T, Lee MM, Ragin RC, Hirobe S, Donahoe PK (1991) Mullerian inhibiting substance production and cleavage is modulated by gonadotropins and steroids. Endocrinology 129: 2985–2992PubMedCrossRefGoogle Scholar
  27. 27.
    Lee MW, Stephens RL (1987) Klinefelter’s syndrome and extragonadal germ cell tumors. Cancer 60: 1053–1055PubMedCrossRefGoogle Scholar
  28. 28.
    Lippe B (1990) Turner syndrome. Endocrinol Metab Clin North Am 20: 121–152Google Scholar
  29. 29.
    Mandel JL, Monaco AP, Nelson DL, Schlessinger D, Willard HF (1992) Genome maps III (X Chromosome). Science 258: 87–102PubMedCrossRefGoogle Scholar
  30. 30.
    Manuel M, Katayama KP, Jones HW Jr (1976) The age of occurrence of gonadal tumors in intersex patients with a Y chromosome. Am J Obstet Gynecol 124: 293–300PubMedGoogle Scholar
  31. 31.
    Martinez-Mora J, Saey JM, Toran N, Isnard R, Perez-Lribarme MM, Egozcue J, Audi L (1991) Male pseudohermaph-roditism due to Leydig cell agnesia and absence of testicular LH receptors. Clin Endocrinol 34: 485–491CrossRefGoogle Scholar
  32. 32.
    Mastroyannis C, Wallach EE (1987) Male pseudohermaph-roditism: Inborn errors in testosterone biosynthesis. Semin Reprod Endocrinol: 26-276Google Scholar
  33. 33.
    McCoshen JA (1982) In vivo sex differentiation of congeneic germinal cell aplastic gonads. Am J Obstet Gynecol 142: 83–88PubMedGoogle Scholar
  34. 34.
    McLaren A (1991) Development of the mammalian gonad: The fate of the supporting cell lineage. Bioessays 13: 151–156PubMedCrossRefGoogle Scholar
  35. 35.
    Morel Y (1991) Gene heterogeneity in adrenal 21-hydroxylase. Presse Med 20: 945–949PubMedGoogle Scholar
  36. 36.
    Muller J (1984) Morphometry and histology of gonads from 12 children and adolescents with the androgen insensitivity (testicular feminization) syndrome. J Clin Endocrinol Metab 59: 785–789PubMedCrossRefGoogle Scholar
  37. 37.
    Murphy GF, Welch WR, Urcuyo R (1979) Brenner tumor and mucinous cystaderoma of borderline malignancy in a patient with Turner’s syndrome. Obstet Gynecol 54: 660–663PubMedGoogle Scholar
  38. 38.
    Nakagome Y, Seki S, Fukutani K, Nagafuchi S, Nakahori Y, Tamura T (1991) PCR detection of distal Yp sequences in an XX true hermaphrodite. Am J Med Genet 41: 112–114PubMedCrossRefGoogle Scholar
  39. 39.
    New MI (1992) Genetic disorders of adrenal hormone synthesis. Horm Res 37 (suppl 3): 22–33PubMedCrossRefGoogle Scholar
  40. 40.
    Page DC (1987) Hypothesis: A Y-chromosomeal gene causes gonadoblastoma in dysgenetic gonads. Development 101 (suppl): 151–155PubMedGoogle Scholar
  41. 41.
    Pereira ET, Cabal de Almeida JC, Gunha ACYRG, Patton M, Taylor R, Jeffery S (1991) Use of probes for ZFY, SRY, and the Y pseudoautosomal boundary in XX males, XX true hermaphrodites and an XX female. J Med Genet 28: 591–595PubMedCrossRefGoogle Scholar
  42. 42.
    Pierre-Louis ML, Kovi J, Sampson CC, Worrell RG, Rosser SB (1983) Ultrastructure of the gonads in the testicular feminization syndrome. J Natl Med Assoc 75: 1177–1184PubMedGoogle Scholar
  43. 42a.
    Porter S, Gilles CB (1993) Genomic imprinting. A proposed explanation for the different behaviours of testicular and ovarian germ cell tumors. Med Hypoth 41: 37–41.CrossRefGoogle Scholar
  44. 43.
    Robboy SJ, Miller T, Donahoe PK, Jahre C, Welch WR, Haseltine FP, Miller WA, Atkins L, Crawford JD (1982) Dysgenesis of testicular and streak gonads in the syndrome of mixed gonadal dysgenesis: Perspective derived from a clinicopathologic analysis of twenty-one cases. Hum Pathol 13: 700–716PubMedCrossRefGoogle Scholar
  45. 44.
    Roth LM, Eglen DE, Gonadoblastoma (1989) Immunohis-tochemical and ultrastructural observations. Int J Gynecol Pathol 8: 72–81PubMedCrossRefGoogle Scholar
  46. 44a.
    Russell P, Bannatyne P. (1989) Surgical pathology of the ovaries. New York, Churchill Livingstone, p 492Google Scholar
  47. 45.
    Rutgers JL (1991) Advances in the pathology of intersex conditions. Hum Pathol 22: 884–891PubMedCrossRefGoogle Scholar
  48. 46.
    Rutgers JL, Scully RE (1991) The androgen insensitivity syndrome (testicular feminization). A clinicopathologic study of 43 cases. Int J Gynecol Pathol 10: 126–144PubMedCrossRefGoogle Scholar
  49. 47.
    Sadler TW (1985): Langman’s Medical Embryology, 5th ed. Baltimore: Williams amp; WilkinsGoogle Scholar
  50. 48.
    Saenger P, Levine LS, New MI (1981) Male pseudoher-maphroditism due to abnormal testosterone biosynthesis and metabolism. Clin Andrai 7: 87–97Google Scholar
  51. 49.
    Schwartz ID, Root AW (1991) The Klinefelter syndrome of testicular dysgenesis. Endocrinol Metab Clin North Am 20: 153–163PubMedGoogle Scholar
  52. 50.
    Scully RE (1970) Gonadoblastoma. A review of 74 cases. Cancer 25: 1340–1356PubMedCrossRefGoogle Scholar
  53. 50a.
    Scully RE (1987) Ovarian tumours with functioning stroma. In Fox H, Obstetrical and gynaecological pathology, 2nd ed Churchill Livingstone, New York, 1987; 724–736Google Scholar
  54. 51.
    Scully RE (1991) Gonadal pathology of genetically determined diseases. In Kraus FT, Damjanov (eds), The pathology of reproductive failure (International Academy of Pathology Monograph No. 33). Raltimore, Williams and Wilkins. pp 257–285Google Scholar
  55. 52.
    Shinobara M, Minowada S, Aso Y, Yamada K, Nakahori Y, Tamura T, Nakagome Y (1991) A t(Y;15) translocation with a deletion of the proximal Yq in a boy with mixed gonadal dysgenesis. Hum Genet 86: 422–423Google Scholar
  56. 53.
    Simpson JL, Golbus MS (1992) Genetics in obstetrics and gynecology, 2nd ed, Philadelphia, WR Saunders, 350Google Scholar
  57. 54.
    Sinclair AH, Rerta P, Palmer MS, Hawkins JR, Griffiths RL, Smith MJ, Foster JW, Frischauf AM, Lovell-Radge R, Goodfellow PN (1990) A gene for the human sex determining region encodes a protein with homology to a conserved DNA binding motif. Nature 346: 240–244PubMedCrossRefGoogle Scholar
  58. 55.
    Smith NM, Ryard RW, Rourne AJ (1991) Testicular regression syndrome—a pathological study of 77 cases. Histopa-thology 19: 269–272CrossRefGoogle Scholar
  59. 56.
    Strachan T, White PC (1991) Molecular pathology of steroid 21-hydroxylase deficiency. J Steroid Riochem Mol Riol 40: 537–543CrossRefGoogle Scholar
  60. 57.
    Taketo T, Saeed J, Nishioka Y, Donahoe PK (1991) Delay of testicular maturation in the R6.Y (Dom) ovotestis demonstrated by immunohistochemical staining for müllerian inhibiting substance. Devel Riol 146: 386–395CrossRefGoogle Scholar
  61. 58.
    Talerman A, Verp MS, Senekjian E, Gilewski T, Vogelzang N (1990) True hermaphrodite with bilateral ovotestes, bilateral gonadoblastomas and dysgerminomas, 46 XX/46 XY karyotype, and a successful pregnancy. Cancer 66: 2668–2672PubMedCrossRefGoogle Scholar
  62. 59.
    Thigpen AE, Davis DL, Gautier T, Imperato-McGinley J, Russell DW (1992) The molecular basis of steroid 5 alpha-reductase deficiency in a large Dominican kindred. N Engl J Med 327: 1216–1219PubMedCrossRefGoogle Scholar
  63. 60.
    Tsuji M, Shima H, Yonemura CY, Rrody J, Donahoe PK, Cunha GR (1992) Effect of human recombinant müllerian inhibiting substance on isolated epithelial and mesenchymal cells during müllerian duct regression in the rat. Endocrinology 131: 1481–1488PubMedCrossRefGoogle Scholar
  64. 61.
    van Haarhoven CJHM, Juttmaran JR, Pypers PM, Roukema JA (1991) A testicular tumor in the left adnexa. The persistent müllerian duct syndrome with testicular malignancy. Eur J Surg Oncol 17: 97–98Google Scholar
  65. 62.
    van Niekerk WA, Retief AE (1981) The gonads of human true hermaphrodites. Human Genet 58: 117–122CrossRefGoogle Scholar
  66. 63.
    Van Slooten AJ, Rechner SF, Dodds WG (1992) Recurrent maternal virilization during pregnancy caused by benign androgen-producing ovarian lesions. Am J Obstet Gynecol 167: 1342–1344Google Scholar
  67. 64.
    Voutilainen R, Miller WL (1989) Potential relevance of müllerian inhibiting substance to ovarian physiology. Semin Reprod Endocrinol 7: 88–93CrossRefGoogle Scholar
  68. 65.
    Wallace TM, Levin HS (1990) Mixed gonadal dysgenesis. Arch Pathol Lab Med 114: 679–688PubMedGoogle Scholar
  69. 66.
    Weckworth PF, Johnson HW, Pantzar JT, Coleman GU, Masterson JST, McGillivray R, Tze WJ (1988) Dicentric Y chromosome and mixed disgenesis. J Ural 139: 91–94Google Scholar
  70. 67.
    Welch WR, Robboy SJ (1981) Abnormal sexual development: A classification with emphasis on pathology and neoplastic conditions. Pediatr Andrai 7:71–85CrossRefGoogle Scholar
  71. 68.
    Wertelecki W, Fraurneni JF, Mulvihill JJ (1970) Nongo-nadal neoplasia in Turner’s syndrome. Cancer 26: 485–488PubMedCrossRefGoogle Scholar
  72. 69.
    Yamanaka J, Raker M, Metcalfe S, Hutson JM (1991) Serum levels of müllerian inhibiting substance in boys with cryptorchidism. J Pediatr Surg 26: 621–623PubMedCrossRefGoogle Scholar
  73. 70.
    Zakharia G, Krauss DJ (1990) Sex reversal syndrome (XX male). Urology 36: 322–324PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Stanley J. Robboy
  • Peter F. Bernhardt
  • Tim Parmley

There are no affiliations available

Personalised recommendations