Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism

Journal of Clinical Investigation

Volumn 118, Issue 4, 2008, Pages 1479-1490

  Welsh, Michelle ^a   Saunders, Philippa T K ^a   Fisken, Mark ^a   Scott, Hayley M ^a   Hutchison, Gary R ^a   Smith, Lee B ^a   Sharpe, Richard M ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN; ANTIANDROGEN; FLUTAMIDE; TESTOSTERONE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; AZOOSPERMIA; CONTROLLED STUDY; CRYPTORCHISM; FETUS; HORMONE ACTION; HYPOSPADIAS; IMMUNOHISTOCHEMISTRY; MALE; NONHUMAN; PENIS; PRIORITY JOURNAL; RAT; STATISTICAL ANALYSIS; TESTIS CANCER; TESTOSTERONE SYNTHESIS; TISSUE DIFFERENTIATION; VIRILIZATION;

ANDROGENS; ANIMALS; CRYPTORCHIDISM; EMBRYO, MAMMALIAN; FEMALE; GONADS; HYPOSPADIAS; MALE; RATS; RATS, WISTAR; RECEPTORS, ANDROGEN; SEX CHARACTERISTICS; SEX DIFFERENTIATION; TESTOSTERONE;

EID: 41849107583     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI34241     Document Type: Article

References (59)

1. Koopman, P., Gubbay, J., Vivian, N., Goodfellow, P., and Lovell-Badge, R. 1991. Male development of chromosomally female mice transgenic for Sry. Nature. 351:117-121.
2. Lovell-Badge, R., and Robertson, E. 1990. XY female mice resulting from a heritable mutation in the primary testis-determining gene, Tdy. Development. 109:635-646.
3. Capel, B. 2000. The battle of the sexes. Mech. Dev. 92:89-103.
4. Jost, A. 1972. A new look at the mechanisms controlling sex differentiation in mammals. Johns Hopkins Med. J. 130:38-53.
5. Hughes, I.A., and Deeb, A. 2006. Androgen resistance. Best Pract. Res. Clin. Endocrinol. Metab. 20:577-598.
6. Sarafoglou, K., and Ostrer, H. 2000. Clinical review 111: familial sex reversal: a review. J. Clin. Endocrinol. Metab. 85:483-493.
7. Virtanen, H.E., et al. 2007. Development and descent of the testis in relation to cryptorchidism. Acta Paediatr. 96:622-627.
8. Baskin, L.S., Himes, K., and Colborn, T. 2001. Hypospadias and endocrine disruption: is there a connection? Environ. Health Perspect. 109:1175-1183.
9. Boisen, K.A., et al. 2005. Hypospadias in a cohort of 1072 Danish newborn boys: prevalence and relationship to placental weight, anthropometrical measurements at birth, and reproductive hormone levels at three months of age. J. Clin. Endocrinol. Metab. 90:4041-4046.
10. Boisen, K.A., et al. 2004. Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries. Lancet. 363:1264-1269.
11. Skakkebaek, N.E., Rajpert-De Meyts, E., and Main, K.M. 2001. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum. Reprod. 16:972-978.
12. Fisher, J.S., Macpherson, S., Marchetti, N., and Sharpe, R.M. 2003. Human 'testicular dysgenesis syndrome': a possible model using in-utero exposure of the rat to dibutyl phthalate. Hum. Reprod. 18:1383-1394.
13. Sharpe, R.M., and Skakkebaek, N.E. 2003. Male reproductive disorders and the role of endocrine disruption: advances in understanding and identification of areas for future research. Pure Appl. Chem. 75:2023-2038.
14. Sharpe, R.M. and Skakkebaek, N.E. 2008. Testicular dysgenesis syndrome: mechanistic insights and potential new downstream effects. Fertil. Steril. In press.
15. Peets, E.A., Henson, M.F., and Neri, R. 1974. On the mechanism of the anti-androgenic action of flutamide (alpha-alpha-alpha-trifluoro-2-methyl- 4′-nitro-m-propionotoluidide) in the rat. Endocrinology. 94:532-540.
16. Schaufele, F., et al. 2005. The structural basis of androgen receptor activation: intramolecular and intermolecular amino-carboxy interactions. Proc. Natl. Acad. Sci. U. S. A. 102:9802-9807.
17. Siiteri, P.K., and Wilson, J.D. 1974. Testosterone formation and metabolism during male sexual differentiation in the human embryo. J. Clin. Endocrinol. Metab. 38:113-125.
18. Habert, R., and Picon, R. 1984. Testosterone, dihydrotestosterone and estradiol-17 beta levels in maternal and fetal plasma and in fetal testes in the rat. J. Steroid Biochem. 21:193-198.
19. George, F.W., and Wilson, J. 1994. Gonads and ducts in mammals. In The physiology of reproduction. E. Knobil and J.D. Neill, editors. 2nd ed. Raven Press. New York, New York, USA. 3-28.
20. Reyes, F.I., Winter, J.S., and Faiman, C. 1973. Studies on human sexual development. I. Fetal gonadal and adrenal sex steroids. J. Clin. Endocrinol. Metab. 37:74-78.
21. Price, D. 1936. Normal development of the prostate and seminal vesicles of the rat, with a study of experimental post-natal modifications. Am. J. Anat. 60:79-125.
22. Inomata, T., Eguchi, Y., and Nakamura, T. 1985. Development of the external genitalia in rat fetuses. Jikken Dobutsu. 34:439-444.
23. Jirasek, J.E. 1977. Morphogenesis of the genital system in the human. Birth Defects Orig. Artic. Ser. 13:13-39.
24. Wyndham, N.R. 1943. A morphological study of testicular descent. J. Anat. 77:179-188.
25. Wilhelm, D., and Koopman, P. 2006. The makings of maleness: towards an integrated view of male sexual development. Nat. Rev. Genet. 7:620-631.
26. Amann, R.P., and Veeramachaneni, D.N. 2007. Cryptorchidism in common eutherian mammals. Reproduction. 133:541-561.
27. Goy, R.W., Bercovitch, F.B., and McBrair, M.C. 1988. Behavioral masculinization is independent of genital masculinization in prenatally androgenized female rhesus macaques. Horm. Behav. 22:552-571.
28. Welsh, M., Saunders, P.T., Marchetti, N.I., and Sharpe, R.M. 2006. Androgen-dependent mechanisms of Wolffian duct development and their perturbation by flutamide. Endocrinology. 147:4820-4830.
29. Imperato-McGinley, J., Sanchez, R.S., Spencer, J.R., Yee, B., and Vaughan, E.D. 1992. Comparison of the effects of the 5 alpha-reductase inhibitor finasteride and the antiandrogen flutamide on prostate and genital differentiation: dose-response studies. Endocrinology. 131:1149-1156.
30. McIntyre, B.S., Barlow, N.J., and Foster, P.M. 2002. Male rats exposed to linuron in utero exhibit permanent changes in anogenital distance, nipple retention, and epididymal malformations that result in subsequent testicular atrophy. Toxicol. Sci. 65:62-70.
31. Welsh, M., Saunders, P.T., and Sharpe, R.M. 2007. The critical time window for androgen-dependent development of the Wolffian duct in the rat. Endocrinology. 148:3185-3195.
32. Herman, R.A., Jones, B., Mann, D.R., and Wallen, K. 2000. Timing of prenatal androgen exposure: anatomical and endocrine effects on juvenile male and female rhesus monkeys. Horm. Behav. 38:52-66.
33. Jost, A., Vigier, B., Prepin, J., and Perchellet, J.P. 1973. Studies on sex differentiation in mammals. Recent Prog. Horm. Res. 29:1-41.
34. Ogawa, S., and Nozawa, A. 1969. Effect of prenatal administration of androgen on the reproductive function in female rats. Endocrinol. Jpn. 16:599-607.
35. Stinnakre, M.G. 1975. Period of sensitivity to androgens of the Wolff duct of the rat fetus [In French]. Arch. Anat. Microsc. Morphol. Exp. 64:45-59.
36. Wolf, C.J., Hotchkiss, A., Ostby, J.S., LeBlanc, G.A., and Gray, L.E., Jr. 2002. Effects of prenatal testosterone propionate on the sexual development of male and female rats: a dose-response study. Toxicol. Sci. 65:71-86.
37. Neri, R., Florance, K., Koziol, P., and Van Cleave, S. 1972. A biological profile of a nonsteroidal antiandrogen, SCH 13521 (4′-nitro- 3′trifluoromethylisobutyranilide). Endocrinology. 91:427-437.
38. Anonymous. 2008. Eulexin: clinical pharmacology. RxList: the Internet drug index. http://www.rxlist.com/cgi/generic/flutam_cp.htm.
39. Salazar-Martinez, E., Romano-Riquer, P., Yanez-Marquez, E., Longnecker, M.P., and Hernandez-Avila, M. 2004. Anogenital distance in human male and female newborns: a descriptive, cross-sectional study. Environ. Health. 3:8.
40. Hughes, I.A. 1998. Congenital adrenal hyperplasia - a continuum of disorders. Lancet. 352:752-754.
41. McIntyre, B.S., Barlow, N.J., and Foster, P.M. 2001. Androgen-mediated development in male rat offspring exposed to flutamide in utero: permanence and correlation of early postnatal changes in anogenital distance and nipple retention with malformations in androgen-dependent tissues. Toxicol. Sci. 62:236-249.
42. Mylchreest, E., Sar, M., Cattley, R.C., and Foster, P.M. 1999. Disruption of androgen-regulated male reproductive development by di(n-butyl) phthalate during late gestation in rats is different from flutamide. Toxicol. Appl. Pharmacol. 156:81-95.
43. Foster, P.M., and Harris, M.W. 2005. Changes in androgen-mediated reproductive development in male rat offspring following exposure to a single oral dose of flutamide at different gestational ages. Toxicol. Sci. 85:1024-1032.
44. Spencer, J.R., Torrado, T., Sanchez, R.S., Vaughan, E.D., Jr., and Imperato-McGinley, J. 1991. Effects of flutamide and finasteride on rat testicular descent. Endocrinology. 129:741-748.
45. Baskin, L.S., et al. 1997. The effect of testosterone on androgen receptors and human penile growth. J. Urol. 158:1113-1118.
46. Sajjad, Y., Quenby, S., Nickson, P., Lewis-Jones, D.I., and Vince, G. 2004. Immunohistochemical localization of androgen receptors in the urogenital tracts of human embryos. Reproduction. 128:331-339.
47. Murakami, R. 1987. A histological study of the development of the penis of wild-type and androgen-insensitive mice. J. Anat. 153:223-231.
48. Boas, M., et al. 2006. Postnatal penile length and growth rate correlate to serum testosterone levels: a longitudinal study of 1962 normal boys. Eur. J. Endocrinol. 154:125-129.
49. Sinnecker, G.H., Hiort, O., Nitsche, E.M., Holterhus, P.M., and Kruse, K. 1997. Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor gene. German Collaborative Intersex Study Group. Eur. J. Pediatr. 156:7-14.
50. Gorski, R.A. 2002. Hypothalamic imprinting by gonadal steroid hormones. Adv. Exp. Med. Biol. 511:57-70; discussion 70-73.
51. Knickmeyer, R.C., and Baron-Cohen, S. 2006. Fetal testosterone and sex differences in typical social development and in autism. J. Child Neurol. 21:825-845.
52. Perakis, A., and Stylianopoulou, F. 1986. Effects of a prenatal androgen peak on rat brain sexual differentiation. J. Endocrinol. 108:281-285.
53. Bowman, C.J., Barlow, N.J., Turner, K.J., Wallace, D.G., and Foster, P.M. 2003. Effects of in utero exposure to finasteride on androgen-dependent reproductive development in the male rat. Toxicol. Sci. 74:393-406.
54. Swan, S.H., et al. 2005. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ. Health Perspect. 113:1056-1061.
55. Foster, P.M., Mylchreest, E., Gaido, K.W., and Sar, M. 2001. Effects of phthalate esters on the developing reproductive tract of male rats. Hum. Reprod. Update. 7:231-235.
56. Mylchreest, E., Cattley, R.C., and Foster, P.M. 1998. Male reproductive tract malformations in rats following gestational and lactational exposure to Di(nbutyl) phthalate: an antiandrogenic mechanism? Toxicol. Sci. 43:47-60.
57. Mylchreest, E., Wallace, D.G., Cattley, R.C., and Foster, P.M. 2000. Dose-dependent alterations in androgen-regulated male reproductive development in rats exposed to Di(n-butyl) phthalate during late gestation. Toxicol. Sci. 55:143-151.
58. Scott, H.M., et al. 2007. Role of androgens in fetal testis development and dysgenesis. Endocrinology. 148:2027-2036.
59. Hsieh, M.H., Breyer, B.N., Eisenberg, M.L., and Baskin, L.S. 2008. Associations among hypospadias, cryptorchidism, anogenital distance, and endocrine disruption. Curr. Urol. Rep. In press.