Pubertal administration of DEHP delays puberty, suppresses testosterone production, and inhibits reproductive tract development in male Sprague-Dawley and long-evans rats

Toxicological Sciences

Volumn 111, Issue 1, 2009, Pages 163-178

  Noriega, Nigel C ^a   Howdeshell, Kembra L ^b   Furr, Jonathan ^b   Lambright, Christy R ^b   Wilson, Vickie S ^b   Gray Jr , L Earl ^b  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^b U S ENVIRONMENTAL PROTECTION AGENCY   (United States)

Author keywords

Androgens; Male puberty; Phthalates; Testis pathology

Indexed keywords

ANDROGEN; CHORIONIC GONADOTROPIN; LUTEINIZING HORMONE; PHTHALIC ACID BIS(2 ETHYLHEXYL) ESTER; TESTOSTERONE;

AGE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DELAYED PUBERTY; EPIDIDYMIS; HISTOPATHOLOGY; HYPOTHALAMUS HYPOPHYSIS SYSTEM; LEVATOR ANI MUSCLE; LEYDIG CELL; LONG EVANS RAT; LUTEINIZING HORMONE BLOOD LEVEL; MALE; MALE GENITAL SYSTEM; NONHUMAN; RAT; SEMINAL VESICLE; SERTOLI CELL; SPRAGUE DAWLEY RAT; TESTIS WEIGHT; TESTOSTERONE BLOOD LEVEL; TESTOSTERONE SYNTHESIS;

ANIMALS; BODY WEIGHT; DIETHYLHEXYL PHTHALATE; DOSE-RESPONSE RELATIONSHIP, DRUG; GENITALIA, MALE; LUTEINIZING HORMONE; MALE; ORGAN SIZE; RADIOIMMUNOASSAY; RATS; RATS, LONG-EVANS; RATS, SPRAGUE-DAWLEY; SEXUAL MATURATION; TESTIS; TESTOSTERONE;

RATTUS;

EID: 69049111032     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfp129     Document Type: Article

References (21)

1. Agarwal, D. K., Eustis, S., Lamb, J. C.t., Reel, J. R., and Kluwe, W. M. (1986). Effects of di(2-ethylhexyl) phthalate on the gonadal pathophysiology, sperm morphology, and reproductive performance of male rats. Environ. Health Perspect. 65, 343-350.
2. Akingbemi, B. T., Ge, R., Klinefelter, G. R., Zirkin, B. R., and Hardy, M. P. (2004). Phthalate-induced Leydig cell hyperplasia is associated with multiple endocrine disturbances. Proc. Natl. Acad. Sci. U. S. A. 101, 775-780.
3. Akingbemi, B. T., Youker, R. T., Sottas, C. M., Ge, R., Katz, E., Klinefelter, G. R., Zirkin, B. R., and Hardy, M. P. (2001). Modulation of rat Leydig cell steroidogenic function by di(2-ethylhexyl)phthalate. Biol. Reprod. 65, 1252-1259.
4. Ashby, J., and Lefevre, P. A. (2000). The peripubertal male rat assay as an alternative to the Hershberger castrated male rat assay for the detection of anti-androgens, oestrogens and metabolic modulators. J. Appl. Toxicol. 20, 35-47.
5. Blystone, C. R., Furr, J., Lambright, C. S., Howdeshell, K. L., Ryan, B. C., Wilson, V. S., Leblanc, G. A., and Gray, L. E., Jr. (2007). Prochloraz inhibits testosterone production at dosages below those that affect androgen-dependent organ weights or the onset of puberty in the male Sprague Dawley rat. Toxicol. Sci. 97, 65-74.
6. Foster, P. M., Thomas, L. V., Cook, M. W., and Gangolli, S. D. (1980). Study of the testicular effects and changes in zinc excretion produced by some n-alkyl phthalates in the rat. Toxicol. Appl. Pharmacol. 54, 392-398.
7. Ge, R. S., Chen, G. R., Dong, Q., Akingbemi, B., Sottas, C. M., Santos, M., Sealfon, S. C., Bernard, D. J., and Hardy, M. P. (2007). Biphasic effects of postnatal exposure to diethylhexylphthalate on the timing of puberty in male rats. J. Androl. 28, 513-520.
8. Goldman, J. M., Cooper, R. L., Rehnberg, G. L., Hein, J. F., McElroy, W. K., and Gray, L. E., Jr. (1986). Effects of low subchronic doses of methoxychlor on the rat hypothalamic-pituitary reproductive axis. Toxicol. Appl. Pharmacol. 86, 474-483.
9. Gray, L. E., Jr., Barlow, N. J., Howdeshell, K. L., Ostby, J. S., Furr, J. R., and Gray, C. L. (2009). Transgenerational effects of di (2-ethylhexyl) phthalate in the male CRL: CD(SD) RAT: Added value of assessing multiple offspring per litter. Toxicol. Sci..
10. Gray, L. E., Jr., Ostby, J., Furr, J., Price, M., Veeramachaneni, D. N., and Parks, L. (2000). Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicol. Sci. 58, 350-365.
11. 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.
12. Greenwood, F. C., Hunter, W. M., and Glover, J. S. (1963). The preparation of I-131-labelled human growth hormone of high specific radioactivity. Biochem. J. 89, 114-123.
13. Mahood, I. K., Hallmark, N., McKinnell, C., Walker, M., Fisher, J. S., and Sharpe, R. M. (2005). Abnormal Leydig cell aggregation in the fetal testis of rats exposed to di (n-butyl) phthalate and its possible role in testicular dysgenesis. Endocrinology 146, 613-623.
14. Nagao, T., Ohta, R., Marumo, H., Shindo, T., Yoshimura, S., and Ono, H. (2000). Effect of butyl benzyl phthalate in Sprague-Dawley rats after gavage administration: A two-generation reproductive study. Reprod. Toxicol. 14, 513-532.
15. Parks, L. G., Ostby, J. S., Lambright, C. R., Abbott, B. D., Klinefelter, G. R., Barlow, N. J., and Gray, L. E., Jr. (2000). The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol. Sci. 58, 339-349.
16. Salazar, V., Castillo, C., Ariznavarreta, C., Campon, R., and Tresguerres, J. A. (2004). Effect of oral intake of dibutyl phthalate on reproductive parameters of Long Evans rats and pre-pubertal development of their offspring. Toxicology 205, 131-137.
17. Sjoberg, P., Lindqvist, N. G., and Ploen, L. (1986). Age-dependent response of the rat testes to di(2-ethylhexyl) phthalate. Environ. Health Perspect. 65, 237-242.
18. Steiner, R. A., Bremner, W. J., Clifton, D. K., and Dorsa, D. M. (1984). Reduced pulsatile luteinizing hormone and testosterone secretion with aging in the male rat. Biol. Reprod. 31, 251-258.
19. Tyl, R.W., Myers, C. B.,Marr, M. C., Fail, P. A., Seely, J. C., Brine, D. R., Barter, R. A., and Butala, J. H. (2004). Reproductive toxicity evaluation of dietary butyl benzyl phthalate (BBP) in rats. Reprod. Toxicol. 18, 241-264.
20. Wilson, V. S., Howdeshell, K. L., Lambright, C. S., Furr, J., and Earl Gray, L., Jr. (2007). Differential expression of the phthalate syndrome in male Sprague-Dawley and Wistar rats after in utero DEHP exposure. Toxicol. Lett. 170, 177-184.
21. Wilson, V. S., Lambright, C., Furr, J., Ostby, J., Wood, C., Held, G., and Gray, L. E., Jr. (2004). Phthalate ester-induced gubernacular lesions are associated with reduced insl3 gene expression in the fetal rat testis. Toxicol. Lett. 146, 207-215.