Non-monotonic dose effects of in utero exposure to di(2-ethylhexyl) phthalate (DEHP) on testicular and serum testosterone and anogenital distance in male mouse fetuses

Reproductive Toxicology

Volumn 34, Issue 4, 2012, Pages 614-621

  Do, Rylee Phuong ^a   Stahlhut, Richard W ^b   Ponzi, Davide ^a   vom Saal, Frederick S ^a   Taylor, Julia A ^a  

^a UNIVERSITY OF MISSOURI   (United States)

^b UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

Author keywords

Anogenital distance; DEHP; MEHP; Non monotonic dose response; Phthalates; Testosterone

Indexed keywords

PHTHALIC ACID 2 ETHYLHEXYL MONOESTER; TESTOSTERONE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANOGENITAL DISTANCE; ARTICLE; BODY WEIGHT; CONTROLLED STUDY; DOSE RESPONSE; FEMALE; FETUS; GESTATION PERIOD; GESTATIONAL AGE; LIQUID CHROMATOGRAPHY; LITTER SIZE; MASS SPECTROMETRY; MOUSE; NONHUMAN; PRENATAL EXPOSURE; SEX DIFFERENTIATION; SEX RATIO; TESTIS; TESTIS WEIGHT; TESTOSTERONE BLOOD LEVEL;

ANAL CANAL; ANIMALS; ANIMALS, OUTBRED STRAINS; DIETHYLHEXYL PHTHALATE; DOSE-RESPONSE RELATIONSHIP, DRUG; ENDOCRINE DISRUPTORS; FEMALE; GENITALIA, MALE; MALE; MATERNAL-FETAL EXCHANGE; MICE; PLASTICIZERS; PREGNANCY; TESTIS; TESTOSTERONE;

MUS; RATTUS;

EID: 84867747536     PISSN: 08906238     EISSN: 18731708     Source Type: Journal    
DOI: 10.1016/j.reprotox.2012.09.006     Document Type: Article

References (50)

1. Heudorf U., Mersch-Sundermann V., Angerer J. Phthalates: toxicology and exposure. International Journal of Hygiene and Environmental Health 2007, 210:623-634.
2. Thomas J.A., Thomas M.J. Biological effects of di-(2-ethylhexyl) phthalate and other phthalic acid esters. Critical Reviews in Toxicology 1984, 13:283-317.
3. Latini G. Monitoring phthalate exposure in humans. Clinica Chimica Acta 2005, 361:20-29.
4. Schmitzer J.L., Scheunert I., Korte F. Fate of bis(2-ethylhexyl) [14C]phthalate in laboratory and outdoor soil-plant systems. Journal of Agricultural and Food Chemistry 1988, 36:210-215.
5. Latini G., Verrotti A., De Felice C. DI-2-ethylhexyl phthalate and endocrine disruption: a review. Current Drug Targets: Immune, Endocrine & Metabolic Disorders 2004, 4:37-40.
6. Frederiksen H., Skakkebaek N.E., Andersson A.-M. Metabolism of phthalates in humans. Molecular Nutrition & Food Research 2007, 51:899-911.
7. CDC, Prevention CfDCa. Fourth national report on human exposure to environmental chemicals. Updated tables, February 2012; 2012.
8. Latini G., De Felice C., Presta G., Del Vecchio A., Paris I., Ruggieri F., et al. In utero exposure to di-(2-ethylhexyl)phthalate and duration of human pregnancy. Environmental Health Perspectives 2003, 111.
9. Silva M.J., Reidy J.A., Herbert A.R., Preau J.L., Needham L.L., Calafat A.M. Detection of phthalate metabolites in human amniotic fluid. Bulletin of Environmental Contamination and Toxicology 2004, 72:1226-1231.
10. Green R., Hauser R., Calafat A.M., Weuve J., Schettler T., Ringer S., et al. Use of di(2-ethylhexyl) phthalate-containing medical products and urinary levels of mono(2-ethylhexyl) phthalate in neonatal intensive care unit infants. Environmental Health Perspectives 2005, 113:1222-1225.
11. Howdeshell K.L., Rider C.V., Wilson V.S., Gray L.E. Mechanisms of action of phthalate esters, individually and in combination, to induce abnormal reproductive development in male laboratory rats. Environmental Research 2008, 108:168-176.
12. Bay K., Asklund C., Skakkebaek N.E., Andersson A.M. Testicular dysgenesis syndrome: possible role of endocrine disrupters. Best Practice and Research: Clinical Endocrinology and Metabolism 2006, 20:77-90.
13. Sonne S.B., Kristensen D.M., Novotny G.W., Olesen I.A., Nielsen J.E., Skakkebæk N.E., et al. Testicular dysgenesis syndrome and the origin of carcinoma in situ testis. International Journal of Andrology 2008, 31:275-287.
14. Fisher J.S. Environmental anti-androgens and male reproductive health: focus on phthalates and testicular dysgenesis syndrome. Reproduction 2004, 127:305-315.
15. Foster P.M.D. Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters. International Journal of Andrology 2006, 29:140-147.
16. Hannas B.R., Lambright C.S., Furr J., Howdeshell K.L., Wilson V.S., Gray L.E. Dose-response assessment of fetal testosterone production and gene expression levels in rat testes following in utero exposure to diethylhexyl phthalate, diisobutyl phthalate, diisoheptyl phthalate, and diisononyl phthalate. Toxicological Sciences 2011, 123:206-216.
17. Wilson V.S., Howdeshell K.L., Lambright C.S., Furr J., Earl Gray L. Differential expression of the phthalate syndrome in male Sprague-Dawley and Wistar rats after in utero DEHP exposure. Toxicology Letters 2007, 170:177-184.
18. Akingbemi B.T., Youker R.T., Sottas C.M., Ge R., Katz E., Klinefelter G.R., et al. Modulation of rat Leydig cell steroidogenic function by di(2-ethylhexyl)phthalate. Biology of Reproduction 2001, 65:1252-1259.
19. Andrade A.J.M., Grande S.W., Talsness C.E., Grote K., Chahoud I. A dose-response study following in utero and lactational exposure to di-(2-ethylhexyl)-phthalate (DEHP): non-monotonic dose-response and low dose effects on rat brain aromatase activity. Toxicology 2006, 227:185-192.
20. Andrade A.J.M., Grande S.W., Talsness C.E., Grote K., Golombiewski A., Sterner-Kock A., et al. A dose-response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): effects on androgenic status, developmental landmarks and testicular histology in male offspring rats. Toxicology 2006, 225:64-74.
21. Lin H., Ge R.S., Chen G.R., Hu G.X., Dong L., Lian Q.Q., et al. Involvement of testicular growth factors in fetal Leydig cell aggregation after exposure to phthalate in utero. Proceedings of the National Academy of Sciences of the United States of America 2008, 105:7218-7222.
22. Hayashi Y., Ito Y., Yanagiba Y., Kamijima M., Naito H., Nakajima T. Differences in metabolite burden of di(2-ethylhexyl)phthalate in pregnant and postpartum dams and their offspring in relation to drug-metabolizing enzymes in mice. Archives of Toxicology 2012, 86:563-569.
23. Gray L.E., Ostby J., Furr J., Price M., Veeramachaneni D.N.R., Parks L. Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicological Sciences 2000, 58:350-365.
24. Borch J., Metzdorff S.B., Vinggaard A.M., Brokken L., Dalgaard M. Mechanisms underlying the anti-androgenic effects of diethylhexyl phthalate in fetal rat testis. Toxicology 2006, 223:144-155.
25. Blystone C.R., Kissling G.E., Bishop J.B., Chapin R.E., Wolfe G.W., Foster P.M.D. Determination of the di-(2-ethylhexyl) phthalate (DEHP) NOAEL for reproductive development in the rat: importance of the retention of extra animals to adulthood. Toxicological Sciences 2010, 116:640-646.
26. Wittassek M., Koch H.M., Angerer J., Brüning T. Assessing exposure to phthalates - the human biomonitoring approach. Molecular Nutrition & Food Research 2011, 55:7-31.
27. Swan S.H., Main K.M., Liu F., Stewart S.L., Kruse R.L., Calafat A.M., et al. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environmental Health Perspectives 2005, 118:1056-1061.
28. Swan S.H. Environmental phthalate exposure in relation to reproductive outcomes and other health endpoints in humans. Environmental Research 2008, 108:177-184.
29. vom Saal F.S., Sheehan D.M. Challenging risk assessment. Forum for Applied Research and Public Policy 1998, 1:1-8.
30. Welshons W.V., Thayer K.A., Judy B.M., Taylor J.A., Curran E.M., vom Saal F.S. Large effects from small exposures. I. Mechanisms for endocrine-disrupting chemicals with estrogenic activity. Environmental Health Perspectives 2003, 111.
31. Vandenberg L.N., Colborn T., Hayes T.B., Heindel J.J., Jacobs D.R., Lee D.-H., et al. Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocrine Reviews 2012, 33:378-455.
32. Zoeller R.T., Brown T.R., Doan L.L., Gore A.C., Skakkebaek N.E., Soto A.M., et al. Endocrine-disrupting chemicals and public health protection: a statement of principles from the endocrine society. Endocrinology 2012, 153:4097-4110.
33. vom Saal F.S., Bronson F.H. In utero proximity of female mouse fetuses to males: effect on reproductive performance during later life. Biology of Reproduction 1978, 19:842-853.
34. vom Saal F.S., Quadagno D.M., Even M.D., Keisler L.W., Keisler D.H., Khan S. Paradoxical effects of maternal stress on fetal steroids and postnatal reproductive traits in female mice from different intrauterine positions. Biology of Reproduction 1990, 43:751-761.
35. Vandenbergh J.G., Huggett C.L. The anogenital distance index, a predictor of the intrauterine position effects on reproduction in female house mice. Laboratory Animal Science 1995, 45:567-573.
36. Ruhlen R.L., Howdeshell K.L., Mao J., Taylor J.A., Bronson F.H., Newbold R.R., et al. Low phytoestrogen levels in feed increase fetal serum estradiol resulting in the fetal estrogenization syndrome and obesity in CD-1 mice. Environmental Health Perspectives 2008, 116:322-328.
37. Cederroth C.R., Vinciguerra M., Kuhne F., Madani R., Doerge D.R., Visser T.J., et al. A phytoestrogen-rich diet increases energy expenditure and decreases adiposity in mice. Environmental Health Perspectives 2007, 115:1467-1473.
38. vom Saal F.S. Sexual differentiation in litter-bearing mammals: influence of sex of adjacent fetuses in utero. Journal of Animal Science 1989, 67:1824-1840.
39. Even M.D., Dhar M.G., vom Saal F.S. Transport of steroids between fetuses via amniotic fluid in relation to the intrauterine position phenomenon in rats. Journal of Reproduction and Fertility 1992, 96:709-716.
40. Takatori S., Kitagawa Y., Kitagawa M., Nakazawa H., Hori S. Determination of di(2-ethylhexyl)phthalate and mono(2-ethylhexyl)phthalate in human serum using liquid chromatography-tandem mass spectrometry. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences 2004, 804:397-401.
41. Gallavan R.H., Holson J.F., Stump D.G., Knapp J.F., Reynolds V.L. Interpreting the toxicologic significance of alterations in anogenital distance: potential for confounding effects of progeny body weights. Reproductive Toxicology 1999, 13:383-390.
42. Moore R.W., Rudy T.A., Lin T.M., Ko K., Peterson R.E. Abnormalities of sexual development in male rats with in utero and lactational exposure to the antiandrogenic plasticizer di(2-ethylhexyl) phthalate. Environmental Health Perspectives 2001, 109:229-237.
43. Parks L.G., Ostby J.S., Lambright C.R., Abbott B.D., Klinefelter G.R., Barlow N.J., et al. The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicological Sciences 2000, 58:339-349.
44. Diamond M. Clinical implications of the organizational and activational effects of hormones. Hormones and Behavior 2009, 55:621-632.
45. Gaido K.W., Hensley J.B., Liu D., Wallace D.G., Borghoff S., Johnson K.J., et al. Fetal mouse phthalate exposure shows that gonocyte multinucleation is not associated with decreased testicular testosterone. Toxicological Sciences 2007, 97:491-503.
46. Rhomberg L.R., Goodman J.E. Low-dose effects and nonmonotonic dose-responses of endocrine disrupting chemicals: has the case been made?. Regulatory Toxicology and Pharmacology: RTP 2012, 64:130-133.
47. Marsee K., Woodruff T.J., Axelrod D.A., Calafat A.M., Swan S.H. Estimated daily phthalate exposures in a population of mothers of male infants exhibiting reduced anogenital distance. Environmental Health Perspectives 2006, 114:805-809.
48. Soares M.J., Talamantes F. Gestational effects on placental and serum androgen, progesterone and prolactin-like activity in the mouse. Journal of Endocrinology 1982, 95:29-36.
49. vom Saal F.S., Dhar M.G. Blood flow in the uterine loop artery and loop vein is bidirectional in the mouse: implications for transport of steroids between fetuses. Physiology and Behavior 1992, 52:163-171.
50. Skakkebæk N.E., Rajpert-De Meyts E., Main K.M. Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects: opinion. Human Reproduction 2001, 16:972-978.