Journal of Pediatric Urology
Volume 3, Issue 5 , Pages 354-363 , October 2007

Hypospadias and anorectal malformations mediated by defective Eph/ephrin signaling

  • Selcuk Yucel

      Affiliations

    • Department of Urology, University of Texas Southwestern Medical Center at Dallas, 5325 Harry Hines Boulevard, Dallas, TX 75235, USA
    • Department of Urology, Pediatric Urology Section, Akdeniz University School of Medicine, Antalya, Turkey
    • ,
  • Christopher Dravis

      Affiliations

    • Department of Developmental Biology, University of Texas Southwestern Medical Center at Dallas, USA
    • ,
  • Nilda Garcia

      Affiliations

    • Department of Surgery, Division of Pediatric Surgery, University of Texas Southwestern Medical Center at Dallas, USA
    • ,
  • Mark Henkemeyer

      Affiliations

    • Department of Developmental Biology, University of Texas Southwestern Medical Center at Dallas, USA
    • ,
  • Linda A. Baker

      Affiliations

    • Department of Urology, University of Texas Southwestern Medical Center at Dallas, 5325 Harry Hines Boulevard, Dallas, TX 75235, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 214 648 2278; fax: +1 214 648 8786.

Received 18 October 2006 ,Accepted 4 January 2007.

References 

  1. Paulozzi LJ, Erickson D, Jackson RJ. Hypospadias trends in two US surveillance systems. Pediatrics. 1997;100:831–834
  2. Wilson JD, Griffin JE, George FW, Leshin M. The endocrine control of male phenotypic development. Aust J Biol Sci. 1983;36:101–128
  3. Wilson JD, Griffin JE, Russell DW. Steroid 5 alpha-reductase 2 deficiency. Endocr Rev. 1993;14:577
  4. Holmes N, Miller W, Baskin L. Lack of defects in androgen production in children with hypospadias. J Clin Endocrinol Metab. 2004;89:2811–2816
  5. Paulozzi L. International trends in rates of hypospadias and cryptorchidism. Environ Health Perspect. 1999;107:297–302
  6. Sharpe R. The ‘oestrogen hypothesis’ – where do we stand now?. Int J Androl. 2003;26:2–15
  7. Fisher J. Environmental anti-androgens and male reproductive health: focus on phthalates and testicular dysgenesis syndrome. Reproduction. 2004;127:305–315
  8. Brock WA, Pena A. Urological implications of imperforate anus. AUA Update Series. 1991;10:202–207
  9. Metts JC, Kotkin L, Kasper S, Shyr Y, Adams MC, Brock JW. Genital malformations and coexistent urinary tract or spinal anomalies in patients with imperforate anus. J Urol. 1997;158:1298–1300
  10. Lerone M, Bolino A, Martucciello G. The genetics of anorectal malformations: a complex matter. Semin Pediatr Surg. 1997;6:170–179
  11. Christensen K, Madsen CM, Hauge M, Kock K. An epidemiological study of congenital anorectal malformations: 15 Danish birth cohorts followed for 7 years. Pediatr Perinat Epidemiol. 1990;4:269–275
  12. Kiesewetter W, Chang J. Imperforate anus: a five to thirty year follow-up perspective. Prog Pediatr Surg. 1977;10:111–120
  13. Spounge D, Baird P. Imperforate anus in 100,000 consecutive liveborn infants. Am J Med Genet. 1986;2:151–161
  14. Smith E. Incidence, frequency of types, and etiology of anorectal malformations, anorectal malformations in children: update 1988. In:  Stephens F,  Smith E editor. New York, NY: Liss; 1988;p. 231–247
  15. Kim J, Kim P, Hui CC. The VACTERL association: lessons from the Sonic hedgehog pathway. Clin Genet. 2001;59:306–315
  16. Mo R, Kim JH, Zhang J, Chiang C, Hui CC, Kim PC. Anorectal malformations caused by defects in sonic hedgehog signaling. Am J Pathol. 2001;159:765–774
  17. Ramalho-Santos M, Melton DA, McMahon AP. Hedgehog signals regulate multiple aspects of gastrointestinal development. Development. 2000;127:2763–2772
  18. Arsic D, Qi BQ, Beasley SW. Hedgehog in the human: a possible explanation for the VATER association. J Paediatr Child Health. 2002;38:117–121
  19. Kimmel SG, Mo R, Hui CC, Kim PC. New mouse models of congenital anorectal malformations. J Pediatr Surg. 2000;35:227–230[discussion, p. 230–1]
  20. Rogers DS, Paidas CN, Morreale R, Huthcins G. Septation of the anorectal and genitourinary tract in the human embryo: crucial role of the catenoidal shape of the urorectal sulcus. Teratology. 2002;66:144–152
  21. Hynes PJ, Fraher JP. The development of the male genitourinary system. I. The origin of the urorectal septum and the formation of the perineum. Br J Plast Surg. 2004;57:27–36
  22. Colborn T. The wildlife/human connection: modernizing risk decisions. Environ Health Perspect. 1994;102:55–59
  23. Colborn T, vom Saal FS, Soto AM. Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ Health Perspect. 1993;101:378–384
  24. Semenza JC, Tolbert PE, Rubin CH, Guillette LJ, Jackson RJ. Reproductive toxins and alligator abnormalities at Lake Apopka, Florida. Environ Health Perspect. 1997;105:1030–1032
  25. Warner MR, Warner RL, Clinton CW. Reproductive tract calculi, their induction, age incidence, composition and biological effects in Balb/c Crgl mice injected as newborns with estradiol-17beta. Biol Reprod. 1979;20:310–322
  26. Miyagawa S, Buchanan DL, Sato T, Ohta Y, Nishina Y, Iguchi T. Characterization of diethylstilbestrol-induced hypospadias in female mice. Anat Rec. 2002;266:43–50
  27. McLachlan J. Rodent models for perinatal exposure to diethylstilbestrol and their relation to human disease in the male. In:  Herbst AL,  Bern HA editor. Developmental effects of diethylstilbestrol (DES) in pregnancy. New York: Thieme-Stratton, Inc.; 1981;
  28. Kim KS, Torres CR, Yucel S, Raimondo K, Cunha GR, Baskin LS. Induction of hypospadias in a murine model by maternal exposure to synthetic estrogens. Environ Res. 2004;94:267–275
  29. Yucel S, Cavalcanti AG, Desouza A, Wang Z, Baskin LS. The effect of oestrogen and testosterone on the urethral seam of the developing male mouse genital tubercle. BJU Int. 2003;92:1016–1021
  30. Kim KS, Liu W, Cunha GR, Russell DW, Huang H, Shapiro E, et al. Expression of the androgen receptor and 5 alpha-reductase type 2 in the developing human fetal penis and urethra. Cell Tissue Res. 2002;307:145–153
  31. Kurzrock EA, Jegatheesan P, Cunha GR, Baskin LS. Urethral development in the fetal rabbit and induction of hypospadias: a model for human development. J Urol. 2000;164:1786–1792
  32. Mellitzer G, Xu Q, Wilkinson DG. Control of cell behaviour by signalling through Eph receptors and ephrins. Curr Opin Neurobiol. 2000;10:400–408
  33. Wilkinson DG. Multiple roles of EPH receptors and ephrins in neural development. Nat Rev Neurosci. 2001;2:155–164
  34. Knoll B, Drescher U. Ephrin-As as receptors and ephrins in neural development. Nat Rev Neurosci. 2002;25:145–149
  35. Kullander K, Klein R. Mechanisms and functions of eph and ephrin signaling. Nat Rev Mol Cell Biol. 2002;3:475–486
  36. Wang HU, Chen ZF, Anderson DJ. Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell. 1998;93:741–753
  37. Gale NW, Baluk P, Pan L, Kwan M, Holash J, DeChiara TM, et al. Ephrin-B2 selectively marks arterial vessels and neovascularization sites in the adult, with expression in both endothelial and smooth-muscle cells. Dev Biol. 2001;230:151–160
  38. Barrios A, Poole RJ, Durbin L, Brennan C, Holder N, Wilson SW. Eph/Ephrin signaling regulates the mesenchymal-to-epithelial transition of the paraxial mesoderm during somite morphogenesis. Curr Biol. 2003;13:
  39. Dravis C, Yokoyama N, Chumley MJ, Cowan CA, Silvany RE, Shay J, et al. Bidirectional signaling mediated by ephrin-B2 and EphB2 controls urorectal development. Dev Biol. 2004;271:272–290
  40. Lorenzo AJ, Nguyen MT, Sozubir S, Henkemeyer M, Baker LA. Dihydrotestesterone induction of EPHB2 expression in the female genital tubercle mimics male pattern of expression during embryogenesis. J Urol. 2003;170:1618–1623[discussion, p. 1623]
  41. Larsen WJ. Development of the urogenital system, human embryology. 2nd ed.. New York: Churchill Livingstone; 1997;p. 261–310
  42. Fairbanks TJ, De Langhe S, Sala FG, Warburton D, Anderson KD, Bellusci S, et al. Fibroblast growth factor 10 (Fgf10) invalidation results in anorectal malformation in mice. J Ped Surg. 2004;39:360–365
  43. Cowan CA, Henkemeyer M. Ephrins in reverse, park and drive. Trends Cell Biol. 2002;12:339–346

☆ This work was funded in part by NIH R01 DK 59164 (Baker, PI), NIH R01 DK 59164-S1 (Baker, PI – Garcia, Mentoree) and a Children's Medical Center at Dallas Clinical Research Grant (Garcia, PI).

☆☆ Selcuk Yucel is supported by Akdeniz University Scientific Research and Project Unit.

PII: S1477-5131(07)00223-9

doi: 10.1016/j.jpurol.2007.01.199

Journal of Pediatric Urology
Volume 3, Issue 5 , Pages 354-363 , October 2007

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