Volume 10, Issue 1 (7-2012)                   IJRM 2012, 10(1): 7-14 | Back to browse issues page

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Dorostghoal M, Moazedi A A, Zardkaf A. Long-term effects of maternal exposure to Di (2-ethylhexyl) Phthalate on sperm and testicular parameters in Wistar rats offspring. IJRM 2012; 10 (1) :7-14
URL: http://ijrm.ir/article-1-255-en.html
1- , mdorostghoal@yahoo.com
2- Department of Biology, Faculty of Sciences, Shahid Chamran University of Ahwaz, Ahwaz, Iran
Abstract:   (2644 Views)
Background: Phthalate esters have been shown to cause reproductive toxicity in both developing and adult animals.
Objective: This study was designed to assess long-term effects of maternal exposure to Di (2-ethylhexyl) Phthalate (DEHP) on reproductive ability of both neonatal and adult male offspring.
Materials and Methods: 60 female rats randomly divided in four equal groups; vehicle control and three treatment groups that received 10, 100 and 500 mg/kg/day DEHP via gavage during gestation and lactation. At different ages after birth, the volumes of testes were measured by Cavellieri method, testes weights recorded and epididymal sperm samples were assessed for number and gross morphology of spermatozoa. Following tissue processing, seminiferous tubules diameter and germinal epithelium height evaluated with morphometric techniques.
Results: Mean testis weight decreased significantly (p<0.05) in 500 mg/kg/day dose group from 28 to 150 days after birth. Significant decreases were seen in total volumes of testis in 100 (p<0.05) and 500 (p<0.01) mg/kg/day doses groups until 150 days after birth. Seminiferous tubules diameter and germinal epithelium height decreased significantly in 100 (p<0.05) and 500 (p<0.01) mg/kg/day doses groups during postnatal development. Also, mean sperm density in 100 mg/kg/day (p<0.05) and 500 mg/kg/day (p<0.01) doses groups and percent of morphologically normal sperm in highest dose group (p<0.05) decreased significantly until 150 days after birth.
Conclusion: Present study showed that maternal exposure to Di (2-ethylhexyl) Phthalate during gestation and lactation caused to permanent and dose-related reductions of sperm and testicular parameters in rats offspring.
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Type of Study: Original Article |

1. Guillette LJ Jr, Gross TS, Masson GR, Matter JM, Percival HF, Woodward AR. Developmental abnormalities of the gonad and abnormal sex hormone concentrations in juvenile alligators from contaminated and control lakes in Florida. Environ Health Perspect 1994; 102: 680-688. [DOI:10.1289/ehp.94102680]
2. Colborn T, Vom Saal FS, Soto AM. Developmental effects of endocrine disrupting chemicals in wildlife and humans. Environ Health Perspect 1993; 101: 378-384. [DOI:10.1289/ehp.93101378]
3. Auger J, Kunstmann JM, Czyglik F, Jouannet P. Decline in semen quality among fertile men in Paris during the past 20 years. N Engl J Med 1995; 332: 281-285. [DOI:10.1056/NEJM199502023320501]
4. Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Evidence for decreasing quality of semen during the past 50 years. BMJ 1992; 305: 609-613. [DOI:10.1136/bmj.305.6854.609]
5. Takeuchi S, Iida M, Kobayashi S, Jin K, Matsuda T, Kojima H. Differential effects of phthalate esters on transcriptional activities via human estrogen receptors alpha and beta, and androgen receptor. Toxicology 2005; 210: 223-233. [DOI:10.1016/j.tox.2005.02.002]
6. Sultan C, Balaguer P, Terouanne B, Georget V, Paris F, Jeandel C, et al. Environmental xenoestrogens, antiandrogens and disorders of male sexual differentiation. Mol Cell Endocrinol 2001; 178: 99-105. [DOI:10.1016/S0303-7207(01)00430-0]
7. Huber WW, Grasl-Kraupp B, Schulte-Hermann R. Hepatocarcinogenic potential of di (2-ethylhexyl) phthalate in rodents and its implications on human risk. Crit Rev Toxicol 1996; 26: 365-481. [DOI:10.3109/10408449609048302]
8. Silva MJ, Reidy JA, Herbert AR, Preau Jr JL, Needham LL, Calafat AM. Detection of phthalate metabolites in human amniotic fluid. Bull Environ. Contam Toxicol 2004; 72: 1226-1231. [DOI:10.1007/s00128-004-0374-4]
9. Mortensen GK, Main KM, Andersson AM, Leffers H, Skakkebaek NE. Determination of phthalate monoesters in human milk, consumer milk, and infant formula by tandem mass spectrometry (LC- MS- MS). Anal Bioanal Chem 2005; 382:1084-1092. [DOI:10.1007/s00216-005-3218-0]
10. Swan SH, Main KM, Liu F, Stewart SL, Kruse RL, Calafat AM, et al. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Health Perspect 2005; 113: 1056-1061. [DOI:10.1289/ehp.8100]
11. Koch HM, Drexler H, Angerer J. An estimation of the daily intake of Di (2-ethylhexyl) Phthalate (DEHP) and other Phthalates in the general population. Int J Hyg Environ Health 2003; 206: 77-83. [DOI:10.1078/1438-4639-00205]
12. NTP-CERHR. CERHR Expert panel report on Di (2-ethylhexyl) Phthalate. National Toxicology Program, U.S. Department of Health and Human Services; 2000.
13. Main KM, Mortensen GK, Kaleva MM, Boisen KA, Damgaard IN, Chellakooty M, et al. Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in infants three months of age. Environ Health Perspect 2006; 114: 270-276. [DOI:10.1289/ehp.8075]
14. Gray LE Jr, Ostby J, Furr J, Price M, Veeramachaneni DN, Parks L. Perinatal exposure to the phthalates DEHP, BBP, and DINP, but not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicol Sci 2000; 58: 350-365. [DOI:10.1093/toxsci/58.2.350]
15. Imajima T, Shono T, Zakaria O, Suita S. Prenatal Phthalate causes cryptorchidism postnatally by inducing transabdominal ascent of the testis in fetal rats. J Pediatr Surg 1997; 32: 18-21. [DOI:10.1016/S0022-3468(97)90083-X]
16. Shono T, Kai H, Suita S, Nawata H. Time-specific effects of mono(n-butyl) Phthalate on the transabdominal descent of the testes in rat fetuses. BJU Int 2000; 86: 121-125. [DOI:10.1046/j.1464-410x.2000.00710.x]
17. Mylchreest E, Sar M, Cattley RC, Foster PMD. Disruption of androgen-regulated male reproductive development by Di (n-butyl) Phthalate during late gestation in rats is different from flutamide. Toxicol Appl Pharmacol 1999; 156: 81-95. [DOI:10.1006/taap.1999.8643]
18. Fisher JS. Environmental antiandrogens and male reproductive health: focus on Phthalates and testicular dysgenesis syndrome. Reproduction 2004; 127: 305-315. [DOI:10.1530/rep.1.00025]
19. Gray LE, Wolf C, Lambright C, Mann P, Price M, Cooper RL, et al. 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 1999; 15: 94-118. [DOI:10.1191/074823399678846664]
20. Moore RM, Rudy TA, Lin TM, Ko K, Peterson RE. Abnormalities of sexual development in male rats with in utero and lactational exposure to the antiandrogenic plasticizer Di (2-ethylhexyl) Phthalate. Environ Health Perspect 2001; 109: 229-237. [DOI:10.1289/ehp.01109229]
21. Lin H, Lian QQ, Hu GX, Jin Y, Zhang Y, Hardy DO, et al. 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. [DOI:10.1095/biolreprod.108.072975]
22. Christiansen S, Boberg J, Axelstad M, Dalgaard M, Vinggaard AM, Metzdorff SB, et al. Low-dose perinatal exposure to di (2- ethylhexyl) phthalate induces anti-androgenic effects in male rats. Reprod Toxicol 2010; 30: 261-270. [DOI:10.1016/j.reprotox.2010.04.005]
23. Cimini AM, Sulli A, Stefanini S, Serafini B, Moreno S, Rossi L, et al. Effects of Di (2- ethylhexyl) Phthalate on peroxisomes of liver, kidney, and brain of lactating rats and their pups. Cell Mol Biol 1994; 40: 1063-1076.
24. Kim IS, Yang HH. Morphometric study of the testicular interstitium of the rat during postnatal development. Korean J Anat 1999; 32: 849-858.
25. Franca LR, Godinho CL. Testis morphometry, seminiferous epithelium cycle length and daily sperm production in domestic cats (Felis catus). Biol Reprod 2003; 68: 1554-1561. [DOI:10.1095/biolreprod.102.010652]
26. Howard CV, Reed MG. Unbiased Stereology. 1st Ed. Guilford; Bios scientific publishers; 1998.
27. Seed J, Chapin RE, Clegg ED, Dostal LA, Foote RH, Hurtt ME, et al. Methods for assessing sperm motility, morphology, and counts in the rat, rabbit, and dog: a consensus report. ILSI Risk Science Institute Expert Working Group on Sperm Evaluation. Reprod Toxicol 1996; 10: 237-244. [DOI:10.1016/0890-6238(96)00028-7]
28. Narayana K, Prashanthi N, Nayanatara A, Kumar HH, Abhilash K, Bairy KL. Effects of methyl parathion (o, o- dimethyl o-4-nitrophenyl phosphorothioate) on rat sperm morphology and sperm count, but not fertility, are associated with decreased ascorbic acid level in the testis. Mutat Res 2005; 588: 28-34. [DOI:10.1016/j.mrgentox.2005.08.012]
29. Parks LG, Ostby JS, Lambright CR, Abbott BD, Klinefelter GR, Barlow NJ, et al. The plasticizer diethylhexyl phthalate induces malformations by decreasing fetal testosterone synthesis during sexual differentiation in the male rat. Toxicol Sci 2000; 58: 339-349. [DOI:10.1093/toxsci/58.2.339]
30. Arcadi FA, Costa C, Imperatore C, Marchese A, Rapisarda A, Salemi M, et al. Oral toxicity of Bis (2- ethylhexyl) Phthalate during pregnancy and suckling in the Long- Evans rat. Food Chem Toxicol 1998; 36: 963-970. [DOI:10.1016/S0278-6915(98)00065-9]
31. Wolfe GW, Layton KA. Multigeneration reproduction toxicity study in rats: Di (2- ethylhexyl) Phthalate: multigenerational reproductive assessment by continuous breeding when administered to Sprague-Dawley rats in the diet. Unaudited draft. Gaithersburg, MD: TherImmune Research Corporation; 2003 [TRC Study No 7244-200].
32. Sjöberg P, Bondesson U, Gray TJB, Plöen L. Effects of Di (2-ethylhexyl) Phthalate and five of its metabolites on rat testis in vivo and in vitro. Acta Pharmacol Toxicol 1986; 58: 225-233. [DOI:10.1111/j.1600-0773.1986.tb00098.x]
33. Mylchreest E, Cattley RC, Foste PMD. Male reproductive tract malformations in rats following gestational and lactational exposure to Di (n-butyl) Phthalate: An antiandrogenic mechanism? Toxicol Sci 1998: 43; 47-60. [DOI:10.1093/toxsci/43.1.47]
34. Kobayashi K, Miyagawa M, Wang RS, Suda M, Sekiguchi S, Honma T. Effects of in utero and lactational exposure to Di(2-ethylhexyl) Phthalate on somatic and physical development in rat offspring. Industrial Health 2006; 44: 652-660. [DOI:10.2486/indhealth.44.652]
35. Wilson VS, Howdeshell KL, Lambright C, Furr J, Gray Jr LE. Differential expression of the phthalate syndrome in male Sprague Dawley and Wistar rats after in utero DEHP exposure. Toxicol Lett 2007; 170: 177-184. [DOI:10.1016/j.toxlet.2007.03.004]
36. Andrade AJM, Grande SW, Talsness CE, Gericke C, Grote K, Golombiewski A, et al. A dose response study following in utero and lactational exposure to Di (2-ethylhexyl) Phthalate (DEHP): reproductive effects on adult male offspring rats. Toxicology 2006; 228: 85-97. [DOI:10.1016/j.tox.2006.08.020]
37. Dalsenter PR, Santana GM, Grande SW, Andrade AJM, Araujo SL. Phathalate affects the reproductive function and sexual behavior of male Wistar rats. Hum Exp Toxicol 2006; 2: 297-303. [DOI:10.1191/0960327105ht624oa]
38. Howdeshell KL, Rider CV, Wilson VS, Gray Jr LE. Mechanisms of action of phthalate esters, individually and in combination, to induce abnormal reproductive development in male laboratory rats. Environ Res 2008; 108: 168-176. [DOI:10.1016/j.envres.2008.08.009]
39. Gondos B, Berndtson WE. Postnatal and pubertal development. In: Russell LD, Griswold MD. The Sertoli Cell. Clearwater, FL: Cache River Press; 1993; 115-154.
40. Scott HM, Hutchinson GR, Mahood IM, Hallmark N, Welsh M, De Gendt K, et al. Role of androgens in fetal testis development and dysgenesis. Endocrinology 2007; 148: 2027-2036. [DOI:10.1210/en.2006-1622]
41. Griswold MD. The central role of Sertoli cells in spermatogenesis. Semin Cell Dev Biol 1998; 9: 411-416. [DOI:10.1006/scdb.1998.0203]
42. Foster PMD. Disruption of reproductive development in male rat offspring following in utero exposure to phthalate esters. Int J Androl 2006; 29:140-147. [DOI:10.1111/j.1365-2605.2005.00563.x]

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