Mono-(2-ethylhexyl) phthalate directly alters the expression of leydig cell genes and CYP17 lyase activity in cultured rat fetal testis

PLoS ONE

Volumn 6, Issue 11, 2011, Pages

  Chauvigné, François ^a   Plummer, Simon ^b   Lesné, Laurianne ^a   Cravedi, Jean Pierre ^d   Dejucq Rainsford, Nathalie ^a   Fostier, Alexis ^c   Jégou, Bernard ^a  

^a INSERM   (France)

^b CXR Biosciences Ltd   (United Kingdom)

^c Campus de Beaulieu   (France)

^d TOXALIM RESEARCH CENTRE IN FOOD TOXICOLOGY   (France)

Author keywords

[No Author keywords available]

Indexed keywords

3 HYDROXY 3 METHYLGLUTARYL COENZYME A SYNTHASE 1; ACYL COENZYME A DEHYDROGENASE; ACYL COENZYME A OXIDASE 1; ANDROSTANOLONE; ANDROSTENEDIONE; APOLIPOPROTEIN E; ASPARTATE AMINOTRANSFERASE ISOENZYME 2; CYTOCHROME P450 17; CYTOCHROME P450 17A1; EMOPAMIL BINDING PROTEIN; FATTY ACID BINDING PROTEIN; FATTY ACID BINDING PROTEIN 3; FERREDOXIN; FERREDOXIN I; GENE PRODUCT; GERANYLTRANSFERASE; GLUTATHIONE PEROXIDASE 1; GLUTATHIONE TRANSFERASE ALPHA; GLUTATHIONE TRANSFERASE ALPHA 4; HYDROXYMETHYLGLUTARYL COENZYME A SYNTHASE; HYDROXYPROGESTERONE; INHIBIN B; INSULIN LIKE FACTOR 3; PEROXIREDOXIN 2; PHTHALIC ACID 2 ETHYLHEXYL MONOESTER; STEROID 5ALPHA REDUCTASE; STEROL 14ALPHA DEMETHYLASE; TESTOSTERONE; TESTOSTERONE 17BETA DEHYDROGENASE; UNCLASSIFIED DRUG; DRUG DERIVATIVE; LYASE; MONO (2 ETHYLHEXYL)PHTHALATE; MONO-(2-ETHYLHEXYL)PHTHALATE; PHTHALIC ACID BIS(2 ETHYLHEXYL) ESTER; STEROID; STEROID 17ALPHA MONOOXYGENASE;

ACADS GENE; ANIMAL CELL; ANIMAL CELL CULTURE; ANIMAL TISSUE; APOLIPOPROTEIN E GENE; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYCS GENE; CYP51 GENE; CYTOCHROME P450 17A1 GENE; EBP GENE; FABP3 GENE; FAT1 GENE; FDPS GENE; FDX1 GENE; GENE; GENE EXPRESSION; GOT2 GENE; GPX 1 GENE; GSTA4 GENE; HMGCS1 GENE; HSPCA GENE; IN VITRO STUDY; INHA GENE; INHIBIN B GENE; INSL3 GENE; INSULIN LIKE FACTOR 3 GENE; LEYDIG CELL; LRPAP1 GENE; MALE; MICROARRAY ANALYSIS; NONHUMAN; NUCLEOTIDE SEQUENCE; PBP GENE; PRDX2 GENE; RAT; SCARB1 GENE; STAR GENE; STEROIDOGENESIS; TESTIS; TESTOSTERONE SYNTHESIS; ANIMAL; BIOSYNTHESIS; CELL CULTURE; DRUG EFFECT; FETUS; GENE EXPRESSION REGULATION; METABOLISM; PATHOLOGY;

RATTUS;

17-ALPHA-HYDROXYPROGESTERONE; ANIMALS; CELLS, CULTURED; DIETHYLHEXYL PHTHALATE; DIHYDROTESTOSTERONE; FETUS; GENE EXPRESSION REGULATION; LEYDIG CELLS; LYASES; MALE; RATS; STEROID 17-ALPHA-HYDROXYLASE; STEROIDS; TESTIS; TESTOSTERONE;

EID: 80555146628     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0027172     Document Type: Article

References (53)

1. Gray LE Jr, Ostby J, Furr J, Wolf CJ, Lambright C, et al. (2001) Effects of environmental antiandrogens on reproductive development in experimental animals. Hum Reprod Update 7: 248-264.
2. Scott HM, Mason JI, Sharpe RM, (2009) Steroidogenesis in the fetal testis and its susceptibility to disruption by exogenous compounds. Endocr Rev 30 (7): 883-925.
3. Carruthers CM, Foster PM, (2005) Critical window of male reproductive tract development in rats following gestational exposure to di-n-butyl phthalate. Birth Defects Res Part B 74: 179-183.
4. Welsh M, Saunders PT, Fisken M, Scott HM, Hutchison GR, et al. (2008) Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism. J Clin Invest 118 (4): 1479-1490.
5. ATSDR, Agency for Toxic Substances and Disease Registry (2002) Toxicological Profile for Diethyl Phthalate Atlanta, GA Agency for Toxic Substances and Disease Registry Available: http://www.atsdr.cdc.gov/toxprofiles/tp73.html.
6. Kavlock R, Barr D, Boekelheide K, Breslin W, Breysse P, et al. (2006) NTPCERHR Expert Panel Update on the Reproductive and Developmental Toxicity of di(2ethylhexyl) phthalate. Reprod Toxicol 22 (3): 291-399.
7. Swan SH, Main KM, Liu F, Stewart SL, Kruse RL, et al. (2005) Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Health Perspect 113: 1056-1061.
8. Main KM, Mortensen GK, Kaleva MM, Boisen KA, Damgaard IN, 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 (2): 270-276.
9. Meeker JD, Calafat AM, Hauser R, (2009) Urinary metabolites of di(2-ethylhexyl) phthalate are associated with decreased steroid hormone levels in adult men. J Androl 30 (3): 287-297.
10. Pan G, Hanaoka T, Yoshimura M, Zhang S, Wang P, et al. (2006) Decreased serum free testosterone in workers exposed to high levels of di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP): a cross-sectional study in China. Environ Health Perspect 114 (11): 1643-1648.
11. Foster PM, (2006) Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters. Int J Androl 29 (1): 140-147; discussion 181-185.
12. Chauvigné F, Menuet A, Lesné L, Chagnon MC, Chevrier C, et al. (2009) Time- and dose-related effects of di-(2-ethylhexyl) phthalate and its main metabolites on the function of the rat fetal testis in vitro. Environ Health Perspect 117 (4): 515-521.
13. Foster PM, Mylchreest E, Gaido KW, Sar M, (2001) Effects of phthalate esters on the developing reproductive tract of male rats. Hum Reprod Update 7 (3): 231-235.
14. Parks LG, Ostby JS, Lambright CR, Abbott BD, Klinefelter GR, et al. (2000) The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol Sci 58 (2): 339-349.
15. Howdeshell KL, Furr J, Lambright CR, Rider CV, Wilson VS, et al. (2007) Cumulative effects of dibutyl phthalate and diethylhexyl phthalate on male rat reproductive tract development: altered fetal steroid hormones and genes. Toxicol Sci 99 (1): 190-202.
16. Lehmann KP, Phillips S, Sar M, Foster PM, Gaido KW, (2004) Dose-dependent alterations in gene expression and testosterone synthesis in the fetal testes of male rats exposed to di (nbutyl) phthalate. Toxicol Sci 81 (1): 60-68.
17. Plummer S, Sharpe RM, Hallmark N, Mahood IK, Elcombe C, (2007) Time-dependent and compartment-specific effects of in utero exposure to Di(n-butyl) phthalate on gene/protein expression in the fetal rat testis as revealed by transcription profiling and laser capture microdissection. Toxicol Sci 97 (2): 520-532.
18. Thompson CJ, Ross SM, Gaido KW, (2004) Di(n-butyl) phthalate impairs cholesterol transport and steroidogenesis in the fetal rat testis through a rapid and reversible mechanism. Endocrinology 145 (3): 1227-1237.
19. Habert R, Devif I, Gangnerau MN, Lecerf L, (1991) Ontogenesis of the in vitro response of rat testis to gonadotropin-releasing hormone. Mol Cell Endocrinol 82 (2-3): 199-206.
20. Lassurguère J, Livera G, Habert R, Jégou B, (2003) Time-and dose-related effects of estradiol and diethylstilbestrol on the morphology and function of the fetal rat testis in culture. Toxicol Sci 73 (1): 160-169.
21. Fostier A, Jalabert B, (1986) Steroidogenesis in rainbow trout (Salmo gairdnen) at various preovulatory stages: changes in plasma hormone levels and in vivo and in vitro responses of the ovary to salmon gonadotropin. Fish Physiol Biochem 2: 87-99.
22. Chen Jun J, Liang Q, Hua H, Wang Y, Luo G, et al. (2009) Simultaneous determination of 15 steroids in rat blood via gas chromatography-mass spectrometry to evaluate the impact of emasculation on adrenal. Talanta 80: 826-832.
23. Wilson JD, (2001) The role of 5alpha-reduction in steroid hormone physiology. Reprod Fertil Dev 13 (7-8): 673-678.
24. Nef S, Parada LF, (1999) Cryptorchidism in mice mutant for Insl3. Nat Genet 22 (3): 295-299.
25. Zimmermann S, Steding G, Emmen JM, Brinkmann AO, Nayernia K, et al. (1999) Targeted disruption of the Insl3 gene causes bilateral cryptorchidism. Mol Endocrinol 13 (5): 681-691.
26. Majdic G, McNeilly AS, Sharpe RM, Evans LR, Groome NP, et al. (1997) Testiscular expression of inhibin and activin subunits and follistatin in the rat and human fetus and neonate and during postnatal development in the rat. Endocrinology 138 (5): 2136-2147.
27. Scott HM, Hutchison GR, Jobling MS, McKinnell C, Drake AJ, et al. (2008) Relationship between androgen action in the "male programming window," fetal sertoli cell number, and adult testis size in the rat. Endocrinology 149 (10): 5280-5287.
28. Sharpe RM, Skakkebaek NE, (2008) Testicular dysgenesis syndrome: mechanistic insights and potential new downstream effects. Fertil Steril 89 (2 Suppl): 33-38.
29. Jégou B, Auger J, Multigner L, Pineau C, Thonneau P, et al. (1999) The saga of the sperm count decrease in humans and wild and farms animals. In: Gagnon C, editors. The Male Gamete: from basic science to clinical applications Cache River Press, Vienna, USA pp. 445-454.
30. Toppari J, Larsen JC, Christiansen P, Giwercman A, Grandjean P, et al. (1996) Male reproductive health and environmental xenoestrogens. Environ Health Perspect 104 (4): 741-803.
31. Hu GX, Lian QQ, Ge RS, Hardy DO, Li XK, (2009) Phthalate-induced testicular dysgenesis syndrome: Leydig cell influence. Trends Endocrinol Metab 20 (3): 139-145.
32. Gray LE Jr, Ostby J, Furr J, Price M, Veeramachaneni DN, et al. (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 (2): 350-365.
33. Mylchreest E, Sar M, Wallace DG, Foster PM, (2002) Fetal testosterone insufficiency and abnormal proliferation of Leydig cells and gonocytes in rats exposed to di(n-butyl) phthalate. Reprod Toxicol 16 (1): 19-28.
34. Johnson KJ, Hensley JB, Kelso MD, Wallace DG, Gaido KW, (2007) Mapping gene expression changes in the fetal rat testis following acute dibutyl phthalate exposure defines a complex temporal cascade of responding cell types. Biol Reprod 77 (6): 978-989.
35. Lahousse SA, Wallace DG, Liu D, Gaido KW, Johnson KJ, (2006) Testicular gene expression profiling following prepubertal rat mono-(2-ethylhexyl) phthalate exposure suggests a common initial genetic response at fetal and prebubertal ages. Toxicol Sci 93: 369-381.
36. Shultz VD, Phillips S, Sar M, Foster PM, Gaido KW, (2001) Altered gene profiles in fetal rat testes after in utero exposure to di(n-butyl). Toxicol Sci 64: 233-242.
37. Miller WL, Auchus RJ, Geller DH, (1997) The regulation of 17,20 lyase activity. Steroids 62 (1): 133-142 Review.
38. Suna S, Yamaguchi F, Kimura S, Tokuda M, Jitsunari F, (2007) Preventive effect of Dpsicose, one of the rare ketohexoses, on di-(2-ethylhexyl) phthalate (DEHP)-induced testicular injury in rat. Toxicol Lett 173 (2): 107-117.
39. Pandey AV, Miller WL, (2005) Regulation of 17,20 lyase activity by cytochrome b5 and by serine phosphorylation of P450c17. J Biol Chem 280 (14): 13265-13271.
40. Liu K, Lehmann KP, Sar M, Young S, Gaido KW, (2005) Gene expression profiling following in utero exposure to phthalate esters reveals new gene targets in the etiology of testicular dysgenesis. Biol Reprod 73: 180-192.
41. Schiffler B, Kiefer M, Wilken A, Hannemann F, Adolph HW, et al. (2001) The interaction of bovine adrenodoxin with P450SCC1 (cytochrome P450scc) and CYP11B1 (cytochrome P45011beta). Acceleration of reduction and substrate conversion by site-directed mutagenesis of adrenodoxin. J Biol Chem 276: 36225-36232.
42. Svechnikov K, Svechnikova I, Söder O, (2008) Inhibitory effects of mono-ethylhexyl phthalate on steroidogenesis in immature and adult rat Leydig cells in vitro. Reprod Toxicol 25 (4): 485-490.
43. Clewell RA, Campbell JL, Ross SM, Gaido KW, Clewell HJ, et al. (2010) Assesing the relevance of in vitro measures of phthalate inhibition of steroidogenesis for in vivo response. Toxicol in vitro 24: 327-334.
44. Travert C, Fofana M, Carreau S, Le Goff D, (2000) Rat Leydig cells use apolipoprotein E depleted high density lipoprotein to regulate testosterone production. Mol Cell Biochem 213 (1-2): 51-59.
45. Zhang G, Curtiss LK, Wade RL, Dyer CA, (1998) An apolipoprotein E synthetic peptide selectively modulates the transcription of the gene for rat ovarian theca and interstitial cell P450 17alpha-hydroxylase, C17-20 lyase. J Lipid Res 39: 2406-2414.
46. Royo T, Pedragosa MJ, Ayté J, Gil-Gómez G, Vilaró S, et al. (1993) Testis and ovary express the gene for the ketogenic mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase. J Lipid Res 34 (6): 867-874.
47. Bae S, Seong J, Paik Y, (2001) Cholesterol biosynthesis from lanosterol: molecular cloning, chromosomal localization, functional expression and liver-specific gene regulation of rat sterol delta8-isomerase, a cholesterogenic enzyme with multiple functions. Biochem J 353: 689-699.
48. Friry-Santini C, Rouquié D, Kennel P, Tinwell H, Benahmed M, et al. (2007) Correlation between protein accumulation profiles and conventional toxicological findings using a model antiandrogenic compound, flutamide. Toxicol Sci 97 (1): 81-93.
49. Janulis L, Nemeth JA, Yang T, Lang S, Lee C, (2000) Prostatic luminal cell differentiation and prostatic steroid-binding protein (PBP) gene expression are differentially affected by neonatal castration. Prostate 43 (3): 195-204.
50. Vinggaard AM, Nellemann C, Dalgaard M, Jørgensen EB, Andersen HR, (2002) Antiandrogenic effects in vitro and in vivo of the fungicide prochloraz. Toxicol Sci 69 (2): 344-353.
51. McKinnell C, Sharpe RM, Mahood K, Hallmark N, Scott H, et al. (2005) Expression of insulin-like factor 3 protein in the rat testis during fetal and postnatal development and in relation to cryptorchidism induced by in utero exposure to di (n-butyl) phthalate. Endocrinology 146 (10): 4536-4544.
52. Lague E, Tremblay J, (2008) Antagonistic effects of testosterone and the endocrine disruptor mono-(2-Ethylhexyl) phthalate on INSL3 transcription in Leydig cells. Endocrinology 149 (9): 4688-4694.
53. Fan J, Traore K, Li W, Amri H, Huang H, et al. (2010) Molecular mechanisms mediating the effect of mono-(2-ethylhexyl) phthalate on hormone-stimulated steroidogenesis in MA-10 mouse tumor Leydig cells. Endocrinology 151 (7): 3348-3362.