Changes in androgen-mediated reproductive development in male rat offspring following exposure to a single oral dose of flutamide at different gestational ages

Toxicological Sciences

Volumn 85, Issue 2, 2005, Pages 1024-1032

  Foster, Paul M D ^a   Harris, Martha W ^a  

^a NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

Author keywords

Antiandiogen; Disruptor; Endocrine; Flutamide; Gestational exposure

Indexed keywords

ANDROGEN; CORN OIL; FLUTAMIDE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLADDER MALFORMATION; BREAST AREOLA; CONTROLLED STUDY; CRYPTORCHISM; DISEASE SEVERITY; EPIDIDYMIS DISEASE; EPISPADIAS; EXPOSURE; FEEDING; GENE EXPRESSION; GENITAL MALFORMATION; GESTATIONAL AGE; HYPOSPADIAS; INCIDENCE; KIDNEY MALFORMATION; MALE; MALE GENITAL SYSTEM; MALE GENITAL TRACT PARAMETERS; MATING; MORPHOLOGY; NEWBORN; NIPPLE; NONHUMAN; OBSERVATION; PATHOGENESIS; PENIS DISEASE; PERINATAL PERIOD; PRENATAL EXPOSURE; PREPUCE; PROSTATE DISEASE; RAT; SEMINAL VESICLE DISEASE; TESTIS DISEASE; TISSUE TYPES; VAGINA;

ANDROGEN ANTAGONISTS; ANDROGENS; ANIMALS; CRYPTORCHIDISM; EPIDIDYMIS; FEMALE; FLUTAMIDE; GENITALIA, MALE; GESTATIONAL AGE; MALE; PREGNANCY; PRENATAL EXPOSURE DELAYED EFFECTS; RATS; TESTIS;

ANIMALIA; ZEA MAYS;

EID: 20544437132     PISSN: 10966080     EISSN: None     Source Type: Journal    
DOI: 10.1093/toxsci/kfi159     Document Type: Article

References (24)

1. Baskin, L. S., Himes, K., and Colborn, T. (2001). Hypospadias and endocrine disruption: Is there a connection? Environ. Health Perspect. 109, 1175-1183.
2. Berman, D. M., Tian, H., and Russell, D. W. (1995). Expression and regulation of steroid 5α-reductase in the urogenital tract of the fetal rat. Mol. Endocrinol. 9, 1561-1570.
3. Boisen, K. A., Kaleva, M., Main, K. M., Virtanen, H. E., Haavisto, A. M., Schmidt, I. M., Chellakooty, M., Damgaard, I. N., Mau, C., Reunanen, M., et al. (2004). Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries. Lancet 363, 1264-1269.
4. Brucker-Davis, F., Pointis, G., Chevallier, D., and Fenichel, P. (2003). Update on cryptorchidism: Endocrine, environmental and therapeutic aspects. J. Endocrinol. Invest. 26, 575-587.
5. Cain, M. P., Kramer, S. A., Tindall, D. J., and Husmann, D. A. (1995). Flutamide-induced cryptorchidism in the rat is associated with altered gubernacular morphology. Urology 46, 553-558.
6. Chung, L. W., and Ferland-Raymond, G. (1975). Differences among rat sex accessory glands in their neonatal androgen dependency. Endocrinology 97, 145-153.
7. Clark, R. L., Anderson, C. A., Prahalada, S., Robertson, R. T., Lochry, E. A., Leonard, Y. M., Stevens, J. L., and Hoberman, A. M. (1993). Critical developmental periods for effects on male rat genitalia induced by finasteride, a 5 alpha-reductase inhibitor. Toxicol. Appl. Pharmacol. 119, 34-40.
8. George, F. W. (1989). Developmental pattern of 5 alpha-reductase activity in the rat gubernaculum. Endocrinology 124, 727-732.
9. Gray, L. E., Ostby, J. S., and Kelce, W. R. (1994). Developmental effects of an environmental antiandrogen: The fungicide vinclozolin alters sex differentiation of the male rat. Toxicol. Appl. Pharmacol. 129, 46-52.
10. Gray, L. E., Jr., Wolf, C., Lambright, C., Mann, P., Price, M., Cooper, R. L., and Ostby, J. (1999). Administration of potentially antiandrogenic pesticides (procymidone, linuron, iprodione, chlozolinate, p,p′-DDE, and ketoconazole) and toxic substances (dibutyl- and diethylhexyl phthalate, PCB 169, and ethane dimethane sulphonate) during sexual differentiation produces diverse profiles of reproductive malformations in the male rat. Toxicol. Ind. Health 15, 94-118.
11. 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.
12. Kassim, N. M., McDonald, S. W., Reid, O., Bennett, N. K., Gilmore, D. P., and Payne, A. P. (1997). The effects of pre- and postnatal exposure to the nonsteroidal antiandrogen flutamide on testis descent and morphology in the Albino Swiss rat. J. Anat. 190, 577-588.
13. LeBlanc, G. A., Bain, L. J., and Wilson, V. S. (1997). Pesticides: Multiple mechanisms of demasculinization. Mol. Cell. Endocrinol. 126, 1-5.
14. Manson, J. M., and Carr, M. C. (2003). Molecular epidemiology of hypospadias: Review of genetic and environmental risk factors. Birth Defects Res. A Clin. Mol. Teratol. 67, 825-836.
15. McIntyre, B. S., Barlow, N. J., and Foster, P. M. D. (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.
16. McIntyre, B. S., Barlow, N. J., Sar, M., Wallace, D. G., and Foster, P. M. D. (2002). Effects of in utero linuron exposure on rat Wolffian duct development. Reprod. Toxicol. 16, 131-139.
17. Mylchreest, E., Cattley, R. C., and Foster, P. M. D. (1998). Male reproductive tract malformations in rats following gestational and lactational exposure to di(n-butyl) phthalate: An antiandrogenic mechanism? Toxicol. Sci. 43, 47-60.
18. Norgil Damgaard, I., Main, K. M., Toppari, J., and Skakkebaek, N. E. (2002). Impact of exposure to endocrine disrupters in utero and in childhood on adult reproduction. Best Pract. Res. Clin. Endocrinol. Metab. 16, 289-309.
19. Rivas, A., Fisher, J. S., McKinnell, C., Atanassova, N., and Sharpe, R. M. (2002). Induction of reproductive tract developmental abnormalities in the male rat by lowering androgen production or action in combination with a low dose of diethylstilbestrol: Evidence for importance of the androgenestrogen balance. Endocrinology 143, 4797-4808.
20. Schardein, J. (1993). Hormones and hormone antagonists. Dekker, New York.
21. 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.
22. Veyssiere, G., Berger, M., Jean-Faucher, C., de Turckheim, M., and Jean, C. (1982). Testosterone and dihydrotestosterone in sexual ducts and genital tubercle of rabbit fetuses during sexual organogenesis: Effects of fetal decapitation. J. Steroid Biochem. 17, 149-154.
23. Xu, C. J., and Li, D. (1998). Pharmacokinetics of flutamide and its metabolite 2-hydroxyflutamide in normal and hepatic injury rats. Zhongguo Yao Li Xue Bao 19, 39-43.
24. Xu, C. J., and Li, D. (1999). Pharmacokinetics of 2-hydroxyflutamide, a major metabolite of flutamide, in normal and CCl4-poisoned rats. Zhongguo Yao Li Xue Bao 20, 655-658.