Combined exposure to endocrine disrupting pesticides impairs parturition, causes pup mortality and affects sexual differentiation in rats

International Journal of Andrology

Volumn 33, Issue 2, 2010, Pages 434-442

  Jacobsen, P R ^a   Christiansen, S ^a   Boberg, J ^a   Nellemann, C ^a   Hass, U ^a  

^a TECHNICAL UNIVERSITY OF DENMARK   (Denmark)

Author keywords

Anogenital distance; Azole fungicides; Combined exposure; Dystochia; Impaired parturition; Nipple retention; Pesticides; Rat

Indexed keywords

ENDOCRINE DISRUPTOR; EPOXYCONAZOLE; ESTRADIOL; FUNGICIDE; MANCOZEB; PESTICIDE; PROCHLORAZ; PROCYMIDONE; PROGESTERONE; TEBUCONAZOLE; TESTOSTERONE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANOGENITAL DISTANCE; ANTHROPOMETRIC PARAMETERS; BIRTH; CONFERENCE PAPER; CONGENITAL MALFORMATION; CONTROLLED STUDY; DOSE RESPONSE; EPIDIDYMIS; FEMALE; GONADAL DYSGENESIS; HORMONE BLOOD LEVEL; HYPOSPADIAS; MALE; MORTALITY; NONHUMAN; PERINATAL MORTALITY; PREGNANCY; PRENATAL DRUG EXPOSURE; PRIORITY JOURNAL; PROSTATE; PUP (RODENT); RAT; SEX DIFFERENTIATION; SEXUAL DEVELOPMENT;

EID: 77949621618     PISSN: 01056263     EISSN: 13652605     Source Type: Journal    
DOI: 10.1111/j.1365-2605.2009.01046.x     Document Type: Conference Paper

References (36)

1. Andersen HR, Schmidt IM, Grandjean P, Jensen TK, Budtz-Jørgensen E, Kjaerstad MB, Baelum J, Nielsen JB, Skakkebaek NE Main KM 2008) Impaired reproductive development in sons of women occupationally exposed to pesticides during pregnancy. Environ Health Perspect 116, 566 572.
2. Blount BC, Silva MJ, Caudill SP, Needham LL, Pirkle JL, Sampson EJ, Lucier GW, Jackson RJ Brock JW 2000) Levels of seven urinary phthalate metabolites in a human reference population. Environ Health Perspect 108, 979 982.
3. Blystone CR, Lambright CS, Howdeshell KL, Furr J, Sternberg RM, Butterworth BC et al. (2007) Sensitivity of fetal rat testicular steroidogenesis to maternal prochloraz exposure and the underlying mechanism of inhibition. Toxicol Sci 97, 512 519.
4. Brock JW, Caudill SP, Silva MJ, Needham LL Hilborn ED 2002) Phthalate monoesters levels in the urine of young children. Bull Environ Contam Toxicol 68, 309 314.
5. Carbone P, Giordano F, Nori F, Mantovani A, Taruscio D, Lauria L Figa-Talamanca I 2007) The possible role of endocrine disrupting chemicals in the aetiology of cryptorchidism and hypospadias: a population-based case-control study in rural Sicily. Int J Androl 30, 3 13.
6. Christiansen S, Scholze M, Axelstad M, Boberg J, Kortenkamp A Hass U 2008) Combined exposure to anti-androgens causes markedly increased frequencies of hypospadias in the rat. Int J Androl 31, 241 248.
7. Christiansen S, Scholze M, Dalgaard M, Vinggaard AM, Axelstad M, Kortenkamp A Hass U 2009) Synergistic disruption of external male sex organ development by a mixture of four antiandrogens. Environ Health Perspect 117, 1839 1846.
8. Damgaard IN, Skakkebaek NE, Toppari J, Virtanen HE, Shen H, Schramm KW, Petersen JH, Jensen TK Main KM 2006) Persistent pesticides in human breast milk and cryptorchidism. Environ Health Perspect 114, 1133 1138.
9. Foster PM 2006) Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters. Int J Androl 29, 140 147.
10. Gallavan RH, Holson JF, Stump DG, Knapp JF Reynolds VL 1999) Interpreting the toxicologic significance of alterations in anogenital distance: potential for confounding effects of progeny body weights. Reprod Toxicol 13, 383 390.
11. Gray LE Jr., Ostby J, Monosson E Kelce WR 1999) Environmental antiandrogens: low doses of the fungicide vinclozolin alter sexual differentiation of the male rat. Toxicol Ind Health 15, 48 64.
12. Gray LE Jr., Wilson VS, Stoker T, Lambright C, Furr J, Noriega N, Howdeshell K, Ankley GT Guillette L 2006) Adverse effects of environmental antiandrogens and androgens on reproductive development in mammals. Int J Androl 29, 96 104.
13. Hass U, Scholze M, Christiansen S, Dalgaard M, Vinggaard AM, Axelstad M, Metzdorff SB Kortenkamp A 2007) Combined exposure to anti-androgens exacerbates disruption of sexual differentiation in the rat. Environ Health Perspect 115 (Suppl. 1 122 128.
14. Hurley PM 1998) Mode of carcinogenic action of pesticides inducing thyroid follicular cell tumors in rodents. Environ Health Perspect 106, 437 445.
15. Kelce WR, Lambright CR, Gray LEJ Roberts KP 1997) Vinclozolin and p,p'-DDE alter androgen-dependent gene expression: in vivo confirmation of an androgen receptor-mediated mechanism. Toxicol Appl Pharmacol 142, 192 200.
16. Kristensen P, Irgens LM, Andersen A, Bye AS Sundheim L 1997) Birth defects among offspring of Norwegian farmers, 1967-1991. Epidemiology 8, 537 544.
17. Laier P, Metzdorff SB, Borch J, Hagen ML, Hass U, Christiansen S et al. (2006) Mechanisms of action underlying the antiandrogenic effects of the fungicide prochloraz. Toxicol Appl Pharmacol 213, 160 171.
18. Main KM, Mortensen GK, Kaleva MM, Boisen KA, Damgaard IN, Chellakooty M et al. (2006) Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age. Environ Health Perspect 114, 270 276.
19. Metzdorff SB, Dalgaard M, Christiansen S, Axelstad M, Hass U, Kiersgaard MK, Scholze M, Kortenkamp A Vinggaard AM 2007) Dysgenesis and histological changes of genitals and perturbations of gene expression in male rats after in utero exposure to antiandrogen mixtures. Toxicol Sci 98, 87 98.
20. Moser VC, Barone S Jr., Smialowicz RJ, Harris MW, Davis BJ, Overstreet D, Mauney M Chapin RE 2001) The effects of perinatal tebuconazole exposure on adult neurological, immunological, and reproductive function in rats. Toxicol Sci 62, 339 352.
21. Nellemann C, Dalgaard M, Holst B, Bonefeld-Jorgensen EC Vinggaard AM 2005) Gene expression changes in rat prostate after activation or blocking of the androgen and estrogen receptor. Mol Cell Endocrinol 237, 25 35.
22. Noriega NC, Ostby J, Lambright C, Wilson VS Gray LE Jr. 2005) Late gestational exposure to the fungicide prochloraz delays the onset of parturition and causes reproductive malformations in male but not female rat offspring. Biol Reprod 72, 1324 1335.
23. Ostby J, Kelce WR, Lambright C, Wolf CJ, Mann P Gray LE Jr. 1999) The fungicide procymidone alters sexual differentiation in the male rat by acting as an androgen-receptor antagonist in vivo and in vitro. Toxicol Ind Health 15, 80 93.
24. Pierik FH, Burdorf A, Deddens JA, Juttmann RE Weber RF 2004) Maternal and paternal risk factors for cryptorchidism and hypospadias: a case-control study in newborn boys. Environ Health Perspect 112, 1570 1576.
25. Rajapakse N, Silva E Kortenkamp A 2002) Combining xenoestrogens at levels below individual no-observed effect concentrations dramatically enhances steroid hormone action. Environ Health Perspect 110, 917 921.
26. Silva E, Rajapakse N Kortenkamp A 2002) Something from "nothing"- eight weak estrogenic chemicals combined at concentrations below NOECs produce significant mixture effects. Environ Sci Technol 36, 1751 1756.
27. Swan SH, Main KM, Liu F, Stewart SL, Kruse RL, Calafat AM et al. (2005) Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Health Perspect 113, 1056 1061.
28. Taxvig C, Hass U, Axelstad M, Dalgaard M, Boberg J, Andeasen HR Vinggaard AM 2007) Endocrine-disrupting activities in vivo of the fungicides tebuconazole and epoxiconazole. Toxicol Sci 100, 464 473.
29. Vinggaard AM, Nellemann C, Dalgaard M, Jorgensen EB Andersen HR 2002) Antiandrogenic effects in vitro and in vivo of the fungicide prochloraz. Toxicol Sci 69, 344 353.
30. Vinggaard AM, Christiansen S, Laier P, Poulsen ME, Breinholt V, Jarfelt K, Jacobsen H, Dalgaard M, Nellemann C Hass U 2005a) Perinatal exposure to the fungicide prochloraz feminizes the male rat offspring. Toxicol Sci 85, 886 897.
31. Vinggaard AM, Jacobsen H, Metzdorff SB, Andersen HR Nellemann C 2005b) Antiandrogenic effects in short-term in vivo studies of the fungicide fenarimol. Toxicology 207, 21 34.
32. Vinggaard AM, Hass U, Dalgaard M, Andersen HR, Bonefeld-Jorgensen E, Christiansen S, Laier P Poulsen ME 2006) Prochloraz: an imidazole fungicide with multiple mechanisms of action. Int J Androl 29, 186 192.
33. Waxman DJ Holloway MG 2009) Sex differences in the expression of hepatic drug metabolizing enzymes. Mol Pharmacol 76, 215 228.
34. Weidner IS, Moller H, Jensen TK Skakkebaek NE 1998) Cryptorchidism and hypospadias in sons of gardeners and farmers. Environ Health Perspect 106, 793 796.
35. Willingham E, Agras K, de Souza J, Konijeti R, Yucel S, Rickie W, Cunha GR Baskin LS 2006) Steroid receptors and mammalian penile development: an unexpected role for progesterone receptor? J Urol 176, 728 733.
36. Wolf C, Lambright C, Mann P, Price M, Cooper RL, Ostby J Gray LE Jr. 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.