Toxicology International (Formerly Indian Journal of Toxicology)

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Impact of DEHP Toxicity on Testis of Rat Leading to Disruption of Testis Histology


Affiliations
1 P. G. Department of Zoology, Magadh University, Bodh Gaya – 824234, Bihar, India
2 P. G. Department of Zoology, Anugrah Narayan College, Patna – 800013, Bihar, India
     

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Di (2-ethyl hexyl) Phthalate (DEHP) is one of the plasticizers widely used in the manufacturing of plastics to make it flexible and durable. Present study is focussed to observe the deleterious effects of DEHP on male reproductive system of animals. For this, 1000 mg/kg body wt. of DEHP was administered to different groups of male Wistar rat for 2, 4, 6 and 8 weeks. After each interval, rats were sacrificed and histological alterations in testis of rats were observed. On hormonal assay, testosterone level decreased significantly in DEHP exposed groups. The histological structure of the testis was also observed to be disrupted significantly with increasing duration of DEHP exposure. Organisation of seminiferous tubule was found distorted and disoriented showing large gaps between them along with degenerated epithelium. Evident changes in morphology of spermatozoa were seen with gradual loss of head and tail structure. Decrease in the number of Leydig cells and sertoli cells were also found suggesting DEHP as a potent toxicant for male reproductive system.


Keywords

DEHP, Histology, Phthalate, Testis, Testosterone, Toxicity.
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  • Lyche JL, Gutleb AC, Bergman A, Eriksen GS, Murk AJ, Ropstad E, Saunders M, Skaare JU. Reproductive and developmental toxicity of phthalates. J Toxicol Environ Health B Crit Rev. 2009 Apr;12(4):225-49. doi: 10.1080/10937400903094091. PMID: 20183522.

  • Clark K, Cousins IT, Mackay D. Assessment of Critical Exposure Pathways. Handb Environ Chem [Internet]. 2003 [cited 2021 Oct 2];3:227–62. Available from: https://link.springer.com/chapter/10.1007/b11468

  • Bonde JP, Flachs EM, Rimborg S, Glazer CH, Giwercman A, Ramlau-Hansen CH, Hougaard KS, Høyer BB, Hærvig KK, Petersen SB, Rylander L, Specht IO, Toft G, Bräuner EV. The epidemiologic evidence linking prenatal and postnatal exposure to endocrine disrupting chemicals with male reproductive disorders: a systematic review and meta-analysis. Hum Reprod Update. 2016 Dec;23(1):104-125. doi: 10.1093/humupd/dmw036. Epub 2016 Sep 21. PMID: 27655588; PMCID: PMC5155570.

  • Swan SH, Main KM, Liu F, Stewart SL, Kruse RL, Calafat AM, Mao CS, Redmon JB, Ternand CL, Sullivan S, Teague JL; Study for Future Families Research Team. Decrease in anogenital distance among male infants with prenatal phthalate exposure. Environ Health Perspect. 2005 Aug;113(8):1056-61. doi: 10.1289/ehp.8100. Erratum in: Environ Health Perspect. 2005 Sep;113(9):A583. PMID: 16079079; PMCID: PMC1280349.

  • Chen J, Wu S, Wen S, Shen L, Peng J, Yan C, Cao X, Zhou Y, Long C, Lin T, He D, Hua Y, Wei G. The Mechanism of Environmental Endocrine Disruptors (DEHP) Induces Epigenetic Transgenerational Inheritance of Cryptorchidism. PLoS One. 2015 Jun 2;10(6):e0126403. doi: 10.1371/journal.pone.0126403. Erratum in: PLoS One. 2015;10(7):e0132749. PMID: 26035430; PMCID: PMC4452760.

  • Lottrup G, Andersson AM, Leffers H, Mortensen GK, Toppari J, Skakkebaek NE, Main KM. Possible impact of phthalates on infant reproductive health. Int J Androl. 2006 Feb;29(1):172-80; discussion 181-5. doi: 10.1111/j.1365-2605.2005.00642.x. PMID: 16466537.

  • Wineland RJ, Bloom MS, Cruze L, Butts CD, Wenzel AG, Unal ER, Kohno S, Willan KB, Brock JW, Newman RB. In utero effects of maternal phthalate exposure on male genital development. Prenat Diagn. 2019 Feb;39(3):209-218. doi: 10.1002/pd.5398. Epub 2019 Feb 7. PMID: 30476355.

  • Specht IO, Toft G, Hougaard KS, Lindh CH, Lenters V, Jönsson BA, Heederik D, Giwercman A, Bonde JP. Associations between serum phthalates and biomarkers of reproductive function in 589 adult men. Environ Int. 2014 May;66:146-56. doi: 10.1016/j.envint.2014.02.002. Epub 2014 Feb 26. PMID: 24583187.

  • Stenz L, Escoffier J, Rahban R, Nef S, Paoloni-Giacobino A. Testicular Dysgenesis Syndrome and Long-Lasting Epigenetic Silencing of Mouse Sperm Genes Involved in the Reproductive System after Prenatal Exposure to DEHP. PLoS One. 2017 Jan 13;12(1):e0170441. doi: 10.1371/journal.pone.0170441. PMID: 28085963; PMCID: PMC5234833.

  • Jensen MS, Anand-Ivell R, Nørgaard-Pedersen B, Jönsson BA, Bonde JP, Hougaard DM, Cohen A, Lindh CH, Ivell R, Toft G. Amniotic fluid phthalate levels and male fetal gonad function. Epidemiology. 2015 Jan;26(1):91-9. doi: 10.1097/EDE.0000000000000198. PMID: 25384265.

  • Desdoits-Lethimonier C, Albert O, Le Bizec B, Perdu E, Zalko D, Courant F, Lesné L, Guillé F, Dejucq-Rainsford N, Jégou B. Human testis steroidogenesis is inhibited by phthalates. Hum Reprod. 2012 May;27(5):1451-9. doi: 10.1093/humrep/des069. Epub 2012 Mar 8. PMID: 22402212.

  • Minatoya M, Araki A, Miyashita C, Sasaki S, Goto Y, Nakajima T, Kishi R. Prenatal di-2-ethylhexyl phthalate exposure and cord blood adipokine levels and birth size: The Hokkaido study on environment and children's health. Sci Total Environ. 2017 Feb 1;579:606-611. doi: 10.1016/j.scitotenv.2016.11.051. Epub 2016 Nov 15. PMID: 27863867.

  • Ito Y, Nakajima T. PPARalpha- and DEHP-Induced Cancers. PPAR Res. 2008;2008:759716. doi: 10.1155/2008/759716. PMID: 18769559; PMCID: PMC2527472.

  • Agarwal DK, Lawrence WH, Turner JE, Autian J. Effects of parenteral di-(2-ethylhexyl)phthalate (DEHP) on gonadal biochemistry, pathology, and reproductive performance of mice. J Toxicol Environ Health. 1989;26(1):39-59. doi: 10.1080/15287398909531232. PMID: 2913333.

  • Chiba K, Kondo Y, Yamaguchi K, Miyake H, Fujisawa M. Inhibition of claudin-11 and occludin expression in rat Sertoli cells by mono-(2-ethylhexyl) phthalate through p44/42 mitogen-activated protein kinase pathway. J Androl. 2012 May-Jun;33(3):368-74. doi: 10.2164/jandrol.111.013664. Epub 2011 Aug 25. PMID: 21868750.

  • Zhang XF, Zhang T, Wang L, Zhang HY, Chen YD, Qin XS, Feng YM, Feng YN, Shen W, Li L. Effects of diethylhexyl phthalate (DEHP) given neonatally on spermatogenesis of mice. Mol Biol Rep. 2013 Nov;40(11):6509-17. doi: 10.1007/s11033-013-2769-y. Epub 2013 Oct 3. PMID: 24057186.

  • Dalsenter PR, Santana GM, Grande SW, Andrade AJ, Araújo SL. Phthalate affect the reproductive function and sexual behavior of male Wistar rats. Hum Exp Toxicol. 2006 Jun;25(6):297-303. doi: 10.1191/0960327105ht624oa. PMID: 16866186.

  • Parmar D, Srivastava SP, Seth PK. Effect of di(2-ethylhexyl)phthalate (DEHP) on spermatogenesis in adult rats. Toxicology. 1986 Dec 1;42(1):47-55. doi: 10.1016/0300-483x(86)90091-0. PMID: 2879365.

  • Noriega NC, Howdeshell KL, Furr J, Lambright CR, Wilson VS, Gray LE Jr. Pubertal administration of DEHP delays puberty, suppresses testosterone production, and inhibits reproductive tract development in male Sprague-Dawley and Long-Evans rats. Toxicol Sci. 2009 Sep;111(1):163-78. doi: 10.1093/toxsci/kfp129. Epub 2009 Jun 15. PMID: 19528224.

  • Fu G, Dai J, Li Z, Chen F, Liu L, Yi L, Teng Z, Quan C, Zhang L, Zhou T, Donkersley P, Song S, Shi Y. The role of STAT3/p53 and PI3K-Akt-mTOR signaling pathway on DEHP-induced reproductive toxicity in pubertal male rat. Toxicol Appl Pharmacol. 2020 Oct 1;404:115151. doi: 10.1016/j.taap.2020.115151. Epub 2020 Jul 22. PMID: 32710958.

  • Voss C, Zerban H, Bannasch P, Berger MR. Lifelong exposure to di-(2-ethylhexyl)-phthalate induces tumors in liver and testes of Sprague-Dawley rats. Toxicology. 2005 Jan 31;206(3):359-71. doi: 10.1016/j.tox.2004.07.016. PMID: 15588926.


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  • Impact of DEHP Toxicity on Testis of Rat Leading to Disruption of Testis Histology

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Authors

Kumari Gouri
P. G. Department of Zoology, Magadh University, Bodh Gaya – 824234, Bihar, India
Preety Sinha
P. G. Department of Zoology, Anugrah Narayan College, Patna – 800013, Bihar, India

Abstract


Di (2-ethyl hexyl) Phthalate (DEHP) is one of the plasticizers widely used in the manufacturing of plastics to make it flexible and durable. Present study is focussed to observe the deleterious effects of DEHP on male reproductive system of animals. For this, 1000 mg/kg body wt. of DEHP was administered to different groups of male Wistar rat for 2, 4, 6 and 8 weeks. After each interval, rats were sacrificed and histological alterations in testis of rats were observed. On hormonal assay, testosterone level decreased significantly in DEHP exposed groups. The histological structure of the testis was also observed to be disrupted significantly with increasing duration of DEHP exposure. Organisation of seminiferous tubule was found distorted and disoriented showing large gaps between them along with degenerated epithelium. Evident changes in morphology of spermatozoa were seen with gradual loss of head and tail structure. Decrease in the number of Leydig cells and sertoli cells were also found suggesting DEHP as a potent toxicant for male reproductive system.


Keywords


DEHP, Histology, Phthalate, Testis, Testosterone, Toxicity.

References