Gonadal development and tumor formation at the crossroads of male and female sex determination

Sexual Development

Volumn 5, Issue 4, 2011, Pages 167-180

  Cools, M ^a   Wolffenbuttel, K P ^b   Drop, S L S ^c   Oosterhuis, J W ^d   Looijenga, L H J ^d  

^a GHENT UNIVERSITY HOSPITAL   (Belgium)

^b Department of Urology ^*  (Netherlands)

^c SOPHIA CHILDREN S HOSPITAL   (Netherlands)

^d JOSEPHINE NEFKENS INSTITUTE   (Netherlands)

Author keywords

Carcinoma in situ; Disorder of sex development; Dysgerminoma; Germ cell tumor; Gonadal development; Gonadoblastoma

Indexed keywords

FORKHEAD TRANSCRIPTION FACTOR; FOXL2 PROTEIN, HUMAN; SOX9 PROTEIN, HUMAN; TRANSCRIPTION FACTOR SOX; TRANSCRIPTION FACTOR SOX9;

ADOLESCENT; ADULT; ANIMAL; CHILD; FEMALE; GENETICS; HUMAN; INFANT; MALE; MIDDLE AGED; NEOPLASM; NEWBORN; OVARY; PHYSIOLOGY; PRENATAL DEVELOPMENT; PRESCHOOL CHILD; REVIEW; RISK FACTOR; SEX DETERMINATION PROCESS; SEX DIFFERENTIATION; SEX DIFFERENTIATION DISORDER; TESTIS; Y CHROMOSOME;

ADOLESCENT; ADULT; ANIMALS; CHILD; CHILD, PRESCHOOL; CHROMOSOMES, HUMAN, Y; DISORDERS OF SEX DEVELOPMENT; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; INFANT; INFANT, NEWBORN; MALE; MIDDLE AGED; NEOPLASMS, GERM CELL AND EMBRYONAL; OVARY; RISK FACTORS; SEX DETERMINATION PROCESSES; SEX DIFFERENTIATION; SOX9 TRANSCRIPTION FACTOR; SOXB1 TRANSCRIPTION FACTORS; TESTIS;

EID: 79960943028     PISSN: 16615425     EISSN: 16615433     Source Type: Journal    
DOI: 10.1159/000329477     Document Type: Article

References (99)

1. Aaronson IA, Aaronson AJ: How should we classify intersex disorders? J Pediatr Urol 6: 443- 446 (2010).
2. Achermann JC, Meeks JJ, Jameson JL: Phenotypic spectrum of mutations in DAX-1 and SF-1 Mol Cell Endocrinol 185: 17-25 (2001). (Pubitemid 33103949)
3. Ahmed SF, Rodie M: Investigation and initial management of ambiguous genitalia. Best Pract Res Clin Endocrinol Metab 24: 197-218 (2010).
4. Ahmed SF, Khwaja O, Hughes IA: The role of a clinical score in the assessment of ambiguous genitalia. BJU Int 85: 120-124 (2000). (Pubitemid 30072462)
5. Aksglaede L, Wikstrom AM, Rajpert-De Meyts E, Dunkel L, Skakkebaek NE, Juul A: Natural history of seminiferous tubule degeneration in Klinefelter syndrome. Hum Reprod Update 12: 39-48 (2006). (Pubitemid 43013745)
6. Barbaro M, Cicognani A, Balsamo A, Löfgren A, Baldazzi L, et al: Gene dosage imbalances in patients with 46,XY gonadal DSD detected by an in-house-designed synthetic probe set for multiplex ligation-dependent probe amplification analysis. Clin Genet 73: 453-464 (2008). (Pubitemid 351517260)
7. Biason-Lauber A: Control of sex development. Best Pract Res Clin Endocrinol Metab 24: 163-186 (2010).
8. Biason-Lauber A, Schoenle EJ: Apparently normal ovarian differentiation in a prepubertal girl with transcriptionally inactive steroidogenic factor 1 (NR5A1/SF-1) and adrenocortical insufficiency. Am J Hum Genet 67: 1563-1568 (2000).
9. Biason-Lauber A, Konrad D, Navratil F, Schoenle EJ: A WNT4 mutation associated with Mullerian-duct regression and virilization in a 46,XX woman. N Engl J Med 351: 792-798 (2004). (Pubitemid 39095314)
10. Biermann K, Steger K: Epigenetics in male germ cells. J Androl 28: 466-480 (2007). (Pubitemid 47057026)
11. Bowles J, Koopman P: Sex determination in mammalian germ cells: Extrinsic versus intrinsic factors. Reproduction 139: 943-958 (2010).
12. Bullejos M, Koopman P: Delayed Sry and Sox9 expression in developing mouse gonads underlies B6-Y(DOM) sex reversal. Dev Biol 278: 473-481 (2005). (Pubitemid 40175043)
13. Canto P, Soderlund D, Reyes E, Mendez JP: Mutations in the desert hedgehog (DHH) gene in patients with 46,XY complete pure gonadal dysgenesis. J Clin Endocrinol Metab 89: 4480-4483 (2004). (Pubitemid 39244458)
14. Cools M, van Aerde K, Kersemaekers AMF, Boter M, Drop SL, et al: Morphological and immunohistochemical differences between gonadal maturation delay and early germ cell neoplasia in patients with undervirilisation syndromes. J Clin Endocrinol Metab 90: 5295-5303 (2005). (Pubitemid 41262289)
15. Cools M, Honecker F, Stoop H, Veltman JD, de Krijger RR, et al: Maturation delay of germ cells in trisomy 21 fetuses results in increased risk for the development of testicular germ cell tumors. Hum Pathol 37: 101-111 (2006a). (Pubitemid 41790509)
16. Cools M, Stoop H, Kersemaekers AM, Drop SL, Wolffenbuttel KP, et al: Gonadoblastoma arising in undifferentiated gonadal tissue within dysgenetic gonads. J Clin Endocrinol Metab 91: 2404-2413 (2006b). (Pubitemid 43855034)
17. Cools M, Drop SL, Wolffenbuttel KP, Oosterhuis JW, Looijenga LH: Germ cell tumors in the intersex gonad: Old paths, new directions, moving frontiers. Endocr Rev 27: 468-484 (2006). (Pubitemid 44213228)
18. Cools M, Looijenga LH, Wolffenbuttel KP, Drop SL: Disorders of sex development: Update on the genetic background, terminology and risk for the development of germ cell tumors. World J Pediatr 5: 93-102 (2009).
19. Cools M, Pleskacova J, Stoop H, Hoebeke P, Van Laecke E, et al: Gonadal pathology and tumor risk in relation to clinical characteristics in patients with 45,X/46,XY mosaicism. J Clin Endocrinol Metab (2011) [E-pub ahead of print].
20. Coutant R, Mallet D, Lahlou N, Bouhours-Nouet N, Guichet A, et al: Heterozygous mutation of steroidogenic factor-1 in 46,XY subjects may mimic partial androgen insensitivity syndrome. J Clin Endocrinol Metab 92: 2868-2873 (2007). (Pubitemid 47236341)
21. Davies JH, Knight EJ, Savage A, Brown J, Malone PS: Evaluation of terminology used to describe disorders of sex development. J Pediatr Urol (2010) [Epub ahead of print].
22. De Baere E, Fellous M, Veitia RA: The transcription factor FOXL2 in ovarian function and dysfunction. Folia Histochem Cytobiol 47:S43-49 (2009).
23. de Jong J, Stoop H, Dohle GR, Bangma CH, Kliffen M, et al: Diagnostic value of OCT3/4 for pre-invasive and invasive testicular germ cell tumours. J Pathol 206: 242-249 (2005). (Pubitemid 40754029)
24. Domenice S, Correa RV, Costa EM, Nishi MY, Vilain E, et al: Mutations in the SRY, DAX1, SF1 and WNT4 genes in Brazilian sex-reversed patients. Braz J Med Biol Res 37: 145-150 (2004). (Pubitemid 38240156)
25. Duffin K, Bayne RA, Childs AJ, Collins C, Anderson RA: The forkhead transcription factor FOXL2 is expressed in somatic cells of the human ovary prior to follicle formation. Mol Hum Reprod 15: 771-777 (2009).
26. Ferraz-de-Souza B, Lin L, Achermann JC: Steroidogenic factor-1 (SF-1, NR5A1) and human disease. Mol Cell Endocrinol 336: 198- 205 (2010).
27. Fleming A, Vilain E: The endless quest for sex determination genes. Clin Genet 67: 15-25 (2005).
28. Gillis AJ, Stoop HJ, Hersmus R, Oosterhuis JW, Sun Y, et al: High-throughput micro- RNAome analysis in human germ cell tumours. J Pathol 213: 319-328 (2007). (Pubitemid 350074022)
29. Grumbach MM, Hughes IA, Conte FA: Disorders of sex differentiation, in Larsen PR, Kronenberg HM, Melmed S, Polonsky KM (eds): Williams Textbook of Endocrinology, 10th ed, pp 842-1002 (W.B. Saunders, Philadelphia 2003).
30. Hersmus R, de Leeuw BH, Wolffenbuttel KP, Drop SL, Oosterhuis JW, et al: New insights into type II germ cell tumor pathogenesis based on studies of patients with various forms of disorders of sex development (DSD). Mol Cell Endocrinol 291: 1-10 (2008a).
31. Hersmus R, Kalfa N, de Leeuw B, Stoop H, Oosterhuis JW, et al: FOXL2 and SOX9 as parameters of female and male gonadal differentiation in patients with various forms of disorders of sex development (DSD). J Pathol 215: 31-38 (2008b). (Pubitemid 351619873)
32. Hersmus R, de Leeuw BH, Stoop H, Bernard P, van Doorn HC, et al: A novel SRY missense mutation affecting nuclear import in a 46,XY female patient with bilateral gonadoblastoma. Eur J Hum Genet 17: 1642-1649 (2009).
33. Hoei-Hansen CE, Holm M, Rajpert-De Meyts E, Skakkebaek NE: Histological evidence of testicular dysgenesis in contralateral biopsies from 218 patients with testicular germ cell cancer. J Pathol 200: 370-374 (2003). (Pubitemid 36827311)
34. Honecker F, Stoop H, de Krijger RR, Chris Lau YF, Bokemeyer C, Looijenga LH: Pathobiological implications of the expression of markers of testicular carcinoma in situ by fetal germ cells. J Pathol 203: 849-857 (2004). (Pubitemid 38961572)
35. Houmard B, Small C, Yang L, Naluai-Cecchini T, Cheng E, et al: Global gene expression in the human fetal testis and ovary. Biol Reprod 81: 438-443 (2009).
36. Hughes I, Houk C, Ahmed SF, Lee PA: Consensus statement on the management of intersex disorders. Arch Dis Child 91: 554-563 (2006). (Pubitemid 44023350)
37. Kanetsky PA, Mitra N, Vardhanabhuti S, Li M, Vaughn DJ, et al: Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer. Nat Genet 41: 811-815 (2009).
38. Kehler J, Tolkunova E, Koschorz B, Pesce M, Gentile L, et al: Oct4 is required for primordial germ cell survival. EMBO Rep 5: 1078-1083 (2004). (Pubitemid 39600207)
39. Kersemaekers AM, Honecker F, Stoop H, Cools M, Molier M, et al: Identification of germ cells at risk for neoplastic transformation in gonadoblastoma. Hum Pathol 36: 512-521 (2005).
40. Kim Y, Kobayashi A, Sekido R, DiNapoli L, Brennan J, et al: Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. PLoS Biol 4:e187 (2006).
41. Kobayashi A, Behringer RR: Developmental genetics of the female reproductive tract in mammals. Nat Rev Genet 4: 969-980 (2003). (Pubitemid 37474644)
42. Kocer A, Reichmann J, Best D, Adams IR: Germ cell sex determination in mammals. Mol Hum Reprod 15: 205-213 (2009).
43. Kohler B, Achermann JC: Update - steroidogenic factor 1 (SF-1, NR5A1). Minerva Endocrinol 35: 73-86 (2010).
44. Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell-Badge R: Male development of chromosomally female mice transgenic for Sry Nature 351: 117-121 (1991). (Pubitemid 21896542)
45. Lau YF: Gonadoblastoma, testicular and prostate cancers, and the TSPY gene. Am J Hum Genet 64: 921-927 (1999).
46. Lau Y, Chou P, Iezzoni J, Alonzo J, Komuves L: Expression of a candidate gene for the gonadoblastoma locus in gonadoblastoma and testicular seminoma. Cytogenet Cell Genet 91: 160-164 (2000). (Pubitemid 32110359)
47. Li Y, Vilain E, Conte F, Rajpert-De Meyts E, Lau YF: Testis-specific protein Y-encoded gene is expressed in early and late stages of gonadoblastoma and testicular carcinoma in situ. Urol Oncol 25: 141-146 (2007a). (Pubitemid 46349748)
48. Li Y, Tabatabai ZL, Lee TL, Hatakeyama S, Ohyama C, et al: The Y-encoded TSPY protein: A significant marker potentially plays a role in the pathogenesis of testicular germ cell tumors. Hum Pathol 38: 1470-1481 (2007b). (Pubitemid 47418969)
49. Liao LM, Green H, Creighton SM, Crouch NS, Conway GS: Service users' experiences of obtaining and giving information about disorders of sex development. BJOG 117: 193-199 (2010).
50. Lin L, Achermann JC: Steroidogenic factor-1 (SF-1, Ad4BP, NR5A1) and disorders of testis development. Sex Dev 2: 200-209 (2008).
51. Looijenga LH, Stoop H, de Leeuw HP, de Gouveia Brazao CA, Gillis AJ, et al: POU5F1 (OCT3/4) identifies cells with pluripotent potential in human germ cell tumors. Cancer Res 63: 2244-2250 (2003a). (Pubitemid 36538633)
52. Looijenga LH, de Leeuw H, van Oorschot M, van Gurp RJ, Stoop H, et al: Stem cell factor receptor (c-KIT) codon 816 mutations predict development of bilateral testicular germ-cell tumors. Cancer Res 63: 7674-7678 (2003b). (Pubitemid 37466695)
53. Looijenga LH, Hersmus R, Oosterhuis JW, Cools M, Drop SL, Wolffenbuttel KP: Tumor risk in disorders of sex development (DSD). Best Pract Res Clin Endocrinol Metab 21: 480-495 (2007). (Pubitemid 47393445)
54. Looijenga LH, Hersmus R, de Leeuw BH, Stoop H, Cools M, et al: Gonadal tumours and DSD. Best Pract Res Clin Endocrinol Metab 24: 291-310 (2010).
55. Lourenco D, Brauner R, Lin L, De Perdigo A, Weryha G, et al: Mutations in NR5A1 associated with ovarian insufficiency. N Engl J Med 360: 1200-1210 (2009).
56. Loveland KL, Schlatt S: Stem cell factor and c- KIT in the mammalian testis: Lessons originating from Mother Nature's gene knockouts. J Endocrinol 153: 337-344 (1997). (Pubitemid 27261243)
57. Matin MM, Walsh JR, Gokhale PJ, Draper JS, Bahrami AR, et al: Specific knockdown of Oct4 and beta2-microglobulin expression by RNA interference in human embryonic stem cells and embryonic carcinoma cells. Stem Cells 22: 659-668 (2004). (Pubitemid 39166924)
58. Meduri G, Bachelot A, Duflos C, Bständig B, Poirot C, et al: FOXL2 mutations lead to different ovarian phenotypes in BPES patients: Case report. Hum Reprod 25: 235-243 (2010).
59. Modi DN, Sane S, Bhartiya D: Accelerated germ cell apoptosis in sex chromosome aneuploid fetal human gonads. Mol Hum Reprod 9: 219-225 (2003). (Pubitemid 36503463)
60. Molyneaux K, Wylie C: Primordial germ cell migration. Int J Dev Biol 48: 537-544 (2004). (Pubitemid 39360404)
61. Nakamura S, Aoki Y, Saito D, Kuroki Y, Fujiyama A, et al: Sox9b/sox9a2-EGFP transgenic medaka reveals the morphological reorganization of the gonads and a common precursor of both the female and male supporting cells. Mol Reprod Dev 75: 472-476 (2008). (Pubitemid 351214148)
62. Nef S, Vassalli JD: Complementary pathways in mammalian female sex determination. J Biol 8: 74 (2009).
63. Niwa H, Miyazaki J, Smith AG: Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet 24: 372-376 (2000). (Pubitemid 30187435)
64. Ogunbiyi JO, Shittu OB, Aghadiuno PU, Lawani J: Seminoma arising in cryptorchid testes in Nigerian males. East Afr Med J 73: 129-132 (1996). (Pubitemid 126354129)
65. Okamura D, Tokitake Y, Niwa H, Matsui Y: Requirement of Oct3/4 function for germ cell specification. Dev Biol 317: 576-584 (2008).
66. Oosterhuis JW, Looijenga LH: Testicular germcell tumours in a broader perspective. Nat Rev Cancer 5: 210-222 (2005). (Pubitemid 40314952)
67. Oram SW, Liu XX, Lee TL, Chan WY, Lau YF: TSPY potentiates cell proliferation and tumorigenesis by promoting cell cycle progression in HeLa and NIH3T3 cells. BMC Cancer 6: 154 (2006).
68. Ottolenghi C, Omari S, Garcia-Ortiz JE, Uda M, Crisponi L, et al: Foxl2 is required for commitment to ovary differentiation. Hum Mol Genet 14: 2053-2062 (2005). (Pubitemid 41418041)
69. Ottolenghi C, Uda M, Crisponi L, Omari S, Cao A, et al: Determination and stability of sex. Bioessays 29: 15-25 (2007). (Pubitemid 46181801)
70. Page DC: Hypothesis: A Y-chromosomal gene causes gonadoblastoma in dysgenetic gonads. Development 101: 151-155 (1987). (Pubitemid 18044531)
71. Parma P, Radi O, Vidal V, Chaboissier MC, Dellambra E, et al: R-spondin1 is essential in sex determination, skin differentiation and malignancy. Nat Genet 38: 1304-1309 (2006). (Pubitemid 44646293)
72. Pasterski V, Prentice P, Hughes IA: Impact of the consensus statement and the new DSD classification system. Best Pract Res Clin Endocrinol Metab 24: 187-195 (2010).
73. Pesce M, Wang X, Wolgemuth DJ, Scholer H: Differential expression of the Oct-4 transcription factor during mouse germ cell differentiation. Mech Dev 71: 89-98 (1998). (Pubitemid 28153521)
74. Piprek RP: Genetic mechanisms underlying male sex determination in mammals. J App Genet 50: 347-360 (2009).
75. Rajpert-De Meyts E, Skakkebaek NE: Expression of the c-KIT protein product in carcinoma- in-situ and invasive testicular germ cell tumours. Int J Androl 17: 85-92 (1994). (Pubitemid 24125601)
76. Rajpert-De Meyts ER, Jorgensen N, Muller J, Skakkebaek NE: Prolonged expression of the c-KIT receptor in germ cells of intersex fetal testes. J Pathol 178: 166-169 (1996). (Pubitemid 26057968)
77. Rajpert-De Meyts E, Jorgensen N, Brondum- Nielsen K, Muller J, Skakkebaek NE: Developmental arrest of germ cells in the pathogenesis of germ cell neoplasia. Apmis 106: 198-204 (1998).
78. Rajpert-De Meyts E, Hanstein R, Jorgensen N, Graem N, Vogt PH, Skakkebaek NE: Developmental expression of POU5F1 (OCT-3/4) in normal and dysgenetic human gonads. Hum Reprod 19: 1338-1344 (2004). (Pubitemid 38807705)
79. Rapley EA, Turnbull C, Al Olama AA, Dermitzakis ET, Linger R, et al: A genome-wide association study of testicular germ cell tumor. Nat Genet 41: 807-810 (2009).
80. Schlessinger D, Garcia-Ortiz JE, Forabosco A, Uda M, Crisponi L, Pelosi E: Determination and stability of gonadal sex. J Androl 31: 16- 25 (2010).
81. Scully RE: Gonadoblastoma. A review of 74 cases. Cancer 25: 1340-1356 (1970).
82. Sekido R: SRY: A transcriptional activator of mammalian testis determination. Int J Biochem Cell Biol 42: 417-420 (2010).
83. Sekido R, Lovell-Badge R: Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer. Nature 453: 930-934 (2008). (Pubitemid 351832560)
84. Sekido R, Lovell-Badge R: Sex determination and SRY: Down to a wink and a nudge? Trends Genet 25: 19-29 (2009).
85. Sharpe RM, McKinnell C, Kivlin C, Fisher JS: Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood. Reproduction 125: 769-784 (2003). (Pubitemid 36722545)
86. Skakkebaek NE: Testicular dysgenesis syndrome: New epidemiological evidence. Int J Androl 27: 189-191 (2004). (Pubitemid 39062079)
87. Skakkebaek NE, Rajpert-De Meyts E, Jorgensen N, Main KM, Leffers H, et al: Testicular cancer trends as 'whistle blowers' of testicular developmental problems in populations. Int J Androl 30: 198-204 (2007). (Pubitemid 47254416)
88. Stoop H, Honecker F, Cools M, de Krijger R, Bokemeyer C, Looijenga LH: Differentiation and development of human female germ cells during prenatal gonadogenesis: An immunohistochemical study. Hum Reprod 20: 1466-1476 (2005). (Pubitemid 40852235)
89. Stoop H, Honecker F, van de Geijn GJ, Gillis AJ, Cools MC, et al: Stem cell factor as a novel diagnostic marker for early malignant germ cells. J Pathol 216: 43-54 (2008).
90. Tannour-Louet M, Han S, Corbett ST, Louet JF, Yatsenko S, et al: Identification of de novo copy number variants associated with human disorders of sexual development. PloS One 5:e15392 (2010).
91. Tomaselli S, Megiorni F, De Bernardo C, Felici A, Marrocco G, et al: Syndromic true hermaphroditism due to an R-spondin1 (RSPO1) homozygous mutation. Hum Mutat 29: 220-226 (2008). (Pubitemid 351240593)
92. Uhlenhaut NH, Jakob S, Anlag K, Eisenberger T, Sekido R, et al: Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation. Cell 139: 1130-1142 (2009).
93. van de Geijn GJ, Hersmus R, Looijenga LH: Recent developments in testicular germ cell tumor research. Birth Defects Res C Embryo Today 87: 96-113 (2009).
94. Verp MS, Simpson JL: Abnormal sexual differentiation and neoplasia. Cancer Genet Cytogenet 25: 191-218 (1987). (Pubitemid 17057632)
95. Virtanen HE, Cortes D, Rajpert-De Meyts E, Ritzén EM, Nordenskjöld A, et al: Development and descent of the testis in relation to cryptorchidism. Acta Paediatr 96: 622-627 (2007). (Pubitemid 46653180)
96. Wilhelm D, Koopman P: The makings of maleness: Towards an integrated view of male sexual development. Nat Rev Genet 7: 620-631 (2006). (Pubitemid 44100519)
97. Wilhelm D, Palmer S, Koopman P: Sex determination and gonadal development in mammals. Physiol Rev 87: 1-28 (2007a). (Pubitemid 46207711)
98. Wilhelm D, Hiramatsu R, Mizusaki H, Widjaja L, Combes AN, et al: SOX9 regulates prostaglandin D synthase gene transcription in vivo to ensure testis development. J Biol Chem 282: 10553-10560 (2007b). (Pubitemid 47093441)
99. Wilhelm D, Washburn LL, Truong V, Fellous M, Eicher EM, Koopman P: Antagonism of the testis- and ovary-determining pathways during ovotestis development in mice. Mech Dev 126: 324-336 (2009).