In utero exposure to diisononyl phthalate caused testicular dysgenesis of rat fetal testis

Toxicology Letters

Volumn 232, Issue 2, 2015, Pages 466-474

  Li, Linxi ^a   Bu, Tiao ^a   Su, Huina ^b   Chen, Zhichuan ^b   Liang, Yuyuan ^b   Zhang, Gaolong ^b   Zhu, Danyan ^b   Shan, Yuanyuan ^b   Xu, Renai ^b   Hu, Yuanyuan ^b   Li, Junwei ^b   Hu, Guoxin ^b   Lian, Qingquan ^b   Ge, Ren Shan ^a,b  

^a THE SECOND AFFILIATED HOSPITAL AND YUYING CHILDREN S HOSPITAL OF WENZHOU MEDICAL UNIVERSITY   (China)

^b WENZHOU MEDICAL UNIVERSITY   (China)

Author keywords

Diisononyl phthalate; Fetal Leydig cell; Gonocyte multinucleation; Leydig cell aggregation; Testicular dysgenesis

Indexed keywords

3(OR 17)BETA HYDROXYSTEROID DEHYDROGENASE; CHOLESTEROL MONOOXYGENASE (SIDE CHAIN CLEAVING); DESMIN; DIISONONYL PHTHALIC ACID; PHTHALIC ACID DERIVATIVE; TESTOSTERONE; UNCLASSIFIED DRUG; DIISONONYL PHTHALATE; PLASTICIZER;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BIRTH RATE; BODY WEIGHT; CELL AGGREGATION; CELL COUNT; CELL SIZE; CONTROLLED STUDY; FEMALE; FETUS; GONADAL DYSGENESIS; IMMUNOHISTOCHEMISTRY; LEYDIG CELL; MALE; NONHUMAN; NUCLEAR SIZE; PRENATAL EXPOSURE; PROTEIN EXPRESSION; RAT; SEMINIFEROUS TUBULE; TESTICULAR DYSGENESIS; TESTIS DEVELOPMENT; TESTIS DISEASE; TESTIS SIZE; TESTOSTERONE SYNTHESIS; ANIMAL; CHEMICALLY INDUCED; DRUG EFFECTS; GENE EXPRESSION; METABOLISM; PATHOLOGY; PREGNANCY; SPRAGUE DAWLEY RAT; TESTIS;

RATTUS; ZEA MAYS;

3-HYDROXYSTEROID DEHYDROGENASES; ANIMALS; DESMIN; FEMALE; GENE EXPRESSION; GONADAL DYSGENESIS; LEYDIG CELLS; MALE; PHTHALIC ACIDS; PLASTICIZERS; PREGNANCY; RATS; RATS, SPRAGUE-DAWLEY; TESTIS; TESTOSTERONE;

EID: 84919795808     PISSN: 03784274     EISSN: 18793169     Source Type: Journal    
DOI: 10.1016/j.toxlet.2014.11.024     Document Type: Article

References (44)

1. Adham I.M., Emmen J.M., Engel W. The role of the testicular factor INSL3 in establishing the gonadal position. Mol. Cell. Endocrinol. 2000, 160(36):11-16.
2. Akingbemi B.T., Ge R., Klinefelter G.R., Zirkin B.R., Hardy M.P. Phthalate-induced Leydig cell hyperplasia is associated with multiple endocrine disturbances. Proc. Natl. Acad. Sci. U. S. A. 2004, 101:775-780.
3. Akingbemi B.T., Youker R.T., Sottas C.M., Ge R., Katz E., Klinefelter G.R., Zirkin B.R., Hardy M.P. Modulation of rat Leydig cell steroidogenic function by di(2-ethylhexyl) phthalate. Biol. Reprod. 2001, 65:1252-1259.
4. Albert O., Jegou B. A critical assessment of the endocrine susceptibility of the human testis to phthalates from fetal life to adulthood. Hum. Reprod. Update 2014, 20:231-249.
5. Beronius A., Molander L., Ruden C., Hanberg A. Facilitating the use of non-standard in vivo studies in health risk assessment of chemicals: a proposal to improve evaluation criteria and reporting. J. Appl. Toxicol. 2014, 34:607-617.
6. Boberg J., Christiansen S., Axelstad M., Kledal T.S., Vinggaard A.M., Dalgaard M., Nellemann C., Hass U. Reproductive and behavioral effects of diisononyl phthalate (DINP) in perinatally exposed rats. Reprod. Toxicol. 2011, 31:200-209.
7. Clewell R.A., Thomas A., Willson G., Creasy D.M., Andersen M.E. A dose response study to assess effects after dietary administration of diisononyl phthalate (DINP) in gestation and lactation on male rat sexual development. Reprod. Toxicol. 2013, 35:70-80.
8. ECB (Ed.), 2003. European union risk assessment report 1,2-benzenedicarboxylic acid, di-C8-10-branched alkyl esters, C9-rich and di-isononyl phthalate (DINP). France.
9. EU, 2005. Directive 2005/84/EC of the European Parliament and of the Council of 14 December 2005. In: Union, O.J.o.t.E. (Ed.), vol. L344, pp. 40-43.
10. EU, 2014. Food Contact Materials Legislative Lists European Commission.
11. 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. Reprod. Toxicol. 1999, 13:383-390.
12. Ge R.-S., Hardy M.P. Regulation of Leydig cells during pubertal development. The Leydig Cell in Health and Disease 2007, Humana Press.
13. Guo J., Zhou H., Su Z., Chen B., Wang G., Wang C.Q., Xu Y., Ge R.S. Comparison of cell types in the rat Leydig cell lineage after ethane dimethanesulfonate treatment. Reproduction 2013, 145:371-380.
14. 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. Toxicol. Sci. 2011, 123:206-216.
15. Heger N.E., Hall S.J., Sandrof M.A., McDonnell E.V., Hensley J.B., McDowell E.N., Martin K.A., Gaido K.W., Johnson K.J., Boekelheide K. Human fetal testis xenografts are resistant to phthalate-induced endocrine disruption. Environ. Health Perspect. 2012, 120:1137-1143.
16. Hellwig J., Freudenberger H., Jackh R. Differential prenatal toxicity of branched phthalate esters in rats. Food Chem. Toxicol. 1997, 35:501-512.
17. Hu G.X., Lian Q.Q., Ge R.S., Hardy D.O., Li X.K. Phthalate-induced testicular dysgenesis syndrome: Leydig cell influence. Trends Endocrinol. Metab. 2009, 20:139-145.
18. Huhtaniemi I., Pelliniemi L.J. Fetal Leydig cells: cellular origin, morphology, life span, and special functional features. Proc. Soc. Exp. Biol. Med. 1992, 201:125-140.
19. IPCS, I.P.o.C.S., 2003. Diisononyl phthalate . http://www.inchem.org/documents/icsc/icsc/eics0831.htm.
20. Joensen U.N., Frederiksen H., Jensen M.B., Lauritsen M.P., Olesen I.A., Lassen T.H., Andersson A.M., Jorgensen N. Phthalate excretion pattern and testicular function: a study of 881 healthy Danish men. Environ. Health Perspect. 2012, 120:1397-1403.
21. Johnson K.J., Heger N.E., Boekelheide K. Of mice and men (and rats): phthalate-induced fetal testis endocrine disruption is species-dependent. Toxicol. Sci. 2012, 129:235-248.
22. Jurewicz J., Radwan M., Sobala W., Ligocka D., Radwan P., Bochenek M., Hawula W., Jakubowski L., Hanke W. Human urinary phthalate metabolites level and main semen parameters, sperm chromatin structure, sperm aneuploidy and reproductive hormones. Reprod. Toxicol. 2013, 42:232-241.
23. Lin H., Ge R.S., Chen G.R., Hu G.X., Dong L., Lian Q.Q., Hardy D.O., Sottas C.M., Li X.K., Hardy M.P. Involvement of testicular growth factors in fetal Leydig cell aggregation after exposure to phthalate in utero. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:7218-7222.
24. Lin H., Lian Q.Q., Hu G.X., Jin Y., Zhang Y., Hardy D.O., Chen G.R., Lu Z.Q., Sottas C.M., Hardy M.P., Ge R.S. In utero and lactational exposures to diethylhexyl-phthalate affect two populations of leydig cells in male long-evans rats. Biol. Reprod. 2009, 80:882-888.
25. Lording D.W., De Kretser D.M. Comparative ultrastructural and histochemical studies of the interstitial cells of the rat testis during fetal and postnatal development. J. Reprod. Fertil. 1972, 29:261-269.
26. Mahood I.K., Hallmark N., McKinnell C., Walker M., Fisher J.S., Sharpe R.M. Abnormal Leydig cell aggregation in the fetal testis of rats exposed to di (n-butyl) phthalate and its possible role in testicular dysgenesis. Endocrinology 2005, 146:613-623.
27. Mahood I.K., McKinnell C., Walker M., Hallmark N., Scott H., Fisher J.S., Rivas A., Hartung S., Ivell R., Mason J.I., Sharpe R.M. Cellular origins of testicular dysgenesis in rats exposed in utero to di(n-butyl) phthalate. Int. J. Androl. 2006, 29:148-154. discussion 181-145.
28. Mahood I.K., Scott H.M., Brown R., Hallmark N., Walker M., Sharpe R.M. In utero exposure to di(n-butyl) phthalate and testicular dysgenesis: comparison of fetal and adult end points and their dose sensitivity. Environ. Health Perspect. 2007, 115(Suppl. 1):55-61.
29. Martino-Andrade A.J., Chahoud I. Reproductive toxicity of phthalate esters. Mol. Nutr. Food Res. 2010, 54:148-157.
30. McKinnell C., Sharpe R.M., Mahood K., Hallmark N., Scott H., Ivell R., Staub C., Jegou B., Haag F., Koch-Nolte F., Hartung S. 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 2005, 146:4536-4544.
31. Mitchell R.T., Childs A.J., Anderson R.A., van den Driesche S., Saunders P.T., McKinnell C., Wallace W.H., Kelnar C.J., Sharpe R.M. Do phthalates affect steroidogenesis by the human fetal testis? Exposure of human fetal testis xenografts to di-n-butyl phthalate. J. Clin. Endocrinol. Metab. 2012, 97:E341-E348.
32. Parks L.G., Ostby J.S., Lambright C.R.A., Abbott B.D., Klinefelter G.R., Barlow N.J., Gray L.E. The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol. Sci. 2000, 58:339-349.
33. Scott, Hutchison G.R., Jobling M.S., McKinnell C., Drake A.J., Sharpe R.M. Relationship between androgen action in the male programming window, fetal sertoli cell number, and adult testis size in the rat. Endocrinology 2008, 149:5280-5287.
34. Sharpe R.M., Skakkebaek N.E. Testicular dysgenesis syndrome: mechanistic insights and potential new downstream effects. Fertil. Steril. 2008, 89:e33-38.
35. Specht I.O., Toft G., Hougaard K.S., Lindh C.H., Lenters V., Jonsson B.A.G., Heederik D., Giwercman A., Bonde J.P.E. Associations between serum phthalates and biomarkers of reproductive function in 589 adult men. Environ. Int. 2014, 66:146-156.
36. Thompson C.J., Ross S.M., Gaido K.W. Di(n-butyl) phthalate impairs cholesterol transport and steroidogenesis in the fetal rat testis through a rapid and reversible mechanism. Endocrinology 2004, 145:1227-1237.
37. van den Driesche S., Walker M., McKinnell C., Scott H.M., Eddie S.L., Mitchell R.T., Seckl J.R., Drake A.J., Smith L.B., Anderson R.A., Sharpe R.M. Proposed role for COUP-TFII in regulating fetal Leydig cell steroidogenesis, perturbation of which leads to masculinization disorders in rodents. PLoS One 2012, 7:e37064.
38. Waterman S.J., Ambroso J.L., Keller L.H., Trimmer G.W., Nikiforov A.I., Harris S.B. Developmental toxicity of di-isodecyl and di-isononyl phthalates in rats. Reprod. Toxicol. 1999, 13:131-136.
39. Welsh M., Saunders P.T., Fisken M., Scott H.M., Hutchison G.R., Smith L.B., Sharpe R.M. Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism. J. Clin. Invest. 2008, 118:1479-1490.
40. WHO/UNEP, U.N.E.P.U.W.H.O.W., 2013. State of the Science of Endocrine Disrupting Chemicals. WHO/UNEP. Organization World Health Organization, Geneva, Switzerland.
41. Wilson V.S., Lambright C., Furr J., Ostby J., Wood C., Held G., Gray L.E. Phthalate ester-induced gubernacular lesions are associated with reduced insl3 gene expression in the fetal rat testis. Toxicol. Lett. 2004, 146:207-215.
42. Wohlfahrt-Veje C., Main K.M., Skakkebaek N.E. Testicular dysgenesis syndrome: foetal origin of adult reproductive problems. Clin. Endocrinol. 2009, 71:459-465.
43. Yao H.H.-C., Barsoum D.I. Fetal Leydig Cells Origin, Regulation, and Functions 2007, Humana Press Inc., Totowa, NJ.
44. Zota A.R., Calafat A.M., Woodruff T.J. Temporal trends in phthalate exposures: findings from the National Health and Nutrition Examination Survey, 2001-2010. Environ. Health Perspect. 2014, 122:235-241.