Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter May 19, 2021

Evaluation of reproductive hormones in Egyptian workers occupationally exposed to di-2-ethylhexyl phthalate (DEHP): a cross-sectional study

  • Fateheya M. Metwally , Asmaa M. Elfiky EMAIL logo , Neven E. Sharaf and Hend Rashad

Abstract

Objectives

Di-2-ethylhexyl phthalate (DEHP) is ubiquitous, known as an endocrine disruptor. DEHP is a widespread prevalence in general and occupational populations which raised great public concerns due to its potentially harmful health effects on the male reproductive system. We aimed to assess occupational levels of DEHP on gonadotropin and gonadal hormones including luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), and sex hormone binding globulin (SHBG) and evaluate its potential effects on Asp327Asn polymorphisms SHBG gene.

Methods

We measured the levels of DEHP of 90 male workers in one of polyvinyl chloride (PVC) industry plant using enzyme-linked immunosorbent assay. Sex hormones were examined and Asp327Asn polymorphisms SHBG gene were detected by PCR-RFLP in all participants.

Results

The workers were divided into low- and high- DEHP exposed groups based on the geometric mean (GM) levels (183.86 U/L) in serum. TT and TT: LH ratio were negatively correlated to DEHP levels (r=−0.213, p=0.038), (r=−0.225, p=0.027), respectively. The linear regression analysis revealed that a 10-fold increase of serum DEHP was found to be associated with 2.07 fold decreased in TT and a 2.26 fold decreased in TT/LH ratio.

Conclusions

Serum testosterone is negatively associated with DEHP exposure in occupational workers.


Corresponding author: Asmaa M. Elfiky, Environmental and Occupational Medicine Department, Environmental Research Division, National Research Centre, Cairo, Egypt, E-mail:

Funding source: National Research Centre

Acknowledgments

The authors are immensely grateful for the National Research Centre for providing the required equipment and lab facilities to complete this research project

  1. Research funding: This research project was funded by National Research Centre Fund.

  2. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  3. Competing interest: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

References

1. Andrade, AJ, 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. https://doi.org/10.1016/j.tox.2006.08.020.Search in Google Scholar PubMed

2. Chiellini, F, Ferri, M, Morelli, A, Dipaola, L, Latini, G. Perspectives on alternatives to phthalate plasticized poly (vinyl chloride) in medical devices applications. Prog Polym Sci 2013;38:1067–88. https://doi.org/10.1016/j.progpolymsci.2013.03.001.Search in Google Scholar

3. Vermeulen, R, Jönsson, BA, Lindh, CH, Kromhout, H. Biological monitoring of carbon disulphide and phthalate exposure in the contemporary rubber industry. Int Arch Occup Environ Health 2005;78:663–9. https://doi.org/10.1007/s00420-005-0017-z.Search in Google Scholar PubMed

4. Heudorf, U, Mersch-Sundermann, V, Angerer, J. Phthalates: toxicology and exposure. Int J Hyg Environ Health 2007;210:623–34. https://doi.org/10.1016/j.ijheh.2007.07.011.Search in Google Scholar PubMed

5. Han, X, Cui, Z, Zhou, N, Ma, M, Li, L, Li, Y, et al.. Urinary phthalate metabolites and male reproductive function parameters in Chongqing general population, China. Int J Hyg Environ Health 2014;217:271–8. https://doi.org/10.1016/j.ijheh.2013.06.006.Search in Google Scholar PubMed

6. Thurston, SW, Mendiola, J, Bellamy, AR, Levine, H, Wang, C, Sparks, A, et al.. Phthalate exposure and semen quality in fertile US men. Andrology 2016;4:632–8. https://doi.org/10.1111/andr.12124.Search in Google Scholar PubMed PubMed Central

7. Caporossi, L, Alteri, A, Campo, G, Paci, E, Tranfo, G, Capanna, S, et al.. Cross sectional study on exposure to BPA and phthalates and semen parameters in men attending a fertility center. Int J Environ Res Publ Health 2020;17:489. https://doi.org/10.3390/ijerph17020489.Search in Google Scholar PubMed PubMed Central

8. Mendiola, J, Meeker, JD, Jørgensen, N, Andersson, AM, Liu, F, Calafat, AM, et al.. Urinary concentrations of di (2‐ethylhexyl) phthalate metabolites and serum reproductive hormones: pooled analysis of fertile and infertile men. J Androl 2012;33:488–98. https://doi.org/10.2164/jandrol.111.013557.Search in Google Scholar PubMed PubMed Central

9. Jurewicz, J, Radwan, M, Sobala, W, Ligocka, D, Radwan, P, Bochenek, M, et al.. Human urinary phthalate metabolites level and main semen parameters, sperm chromatin structure, sperm aneuploidy and reproductive hormones. Reprod Toxicol 2013;42:232–41. https://doi.org/10.1016/j.reprotox.2013.10.001.Search in Google Scholar PubMed

10. Specht, IO, Toft, G, Hougaard, KS, Lindh, CH, Lenters, V, Jönsson, BA, et al.. Associations between serum phthalates and biomarkers of reproductive function in 589 adult men. Environ Int 2014;66:146–56. https://doi.org/10.1016/j.envint.2014.02.002.Search in Google Scholar PubMed

11. Joensen, UN, Frederiksen, H, Jensen, MB, Lauritsen, MP, Olesen, IA, Lassen, TH, et al.. Phthalate excretion pattern and testicular function: a study of 881 healthy Danish men. Environ Health Perspect 2012;120:1397–403. https://doi.org/10.1289/ehp.1205113.Search in Google Scholar PubMed PubMed Central

12. Mendiola, J, Jørgensen, N, Andersson, AM, Calafat, AM, Silva, MJ, Redmon, JB, et al.. Associations between urinary metabolites of di(2-ethylhexyl) phthalate and reproductive hormones in fertile men. Int J Androl 2011;34:369–78. https://doi.org/10.1111/j.1365-2605.2010.01095.x.Search in Google Scholar PubMed PubMed Central

13. Calafat, AM, McKee, RH. Integrating biomonitoring exposure data into the risk assessment process: phthalates [diethyl phthalate and di(2-ethylhexyl) phthalate] as a case study. Environ Health Perspect 2006;114:1783–9. https://doi.org/10.1289/ehp.9059.Search in Google Scholar PubMed PubMed Central

14. Huang, LP, Lee, CC, Hsu, PC, Shih, TS. The association between semen quality in workers and the concentration of di(2-ethylhexyl) phthalate in polyvinyl chloride pellet plant air. Fertil Steril 2011;96:90–4. https://doi.org/10.1016/j.fertnstert.2011.04.093.Search in Google Scholar PubMed

15. Siiteri, PK, Murai, JT, Raymoure, WJ, Kuhn, RW, Hammond, GL, Nisker, JA. The serum transport of steroid hormones. In: Greep, RO, editor. Proceedings of the 1981 Laurentian hormone conference. Boston: Academic Press; 1982.10.1016/B978-0-12-571138-8.50016-0Search in Google Scholar

16. Rosner, W, Hryb, DJ, Kahn, SM, Nakhla, AM, Romas, NA. Interactions of sex hormone-binding globulin with target cells. Mol Cell Endocrinol 2010;316:79–85. https://doi.org/10.1016/j.mce.2009.08.009.Search in Google Scholar PubMed

17. Wen, H-J, Chen, C-C, Wu, M-T, Chen, M-L, Sun, C-W, Wu, W-C, et al.. Phthalate exposure and reproductive hormones and sex-hormone binding globulin before puberty–Phthalate contaminated-foodstuff episode in Taiwan. PloS One 2017;12:e0175536. https://doi.org/10.1371/journal.pone.0175536.Search in Google Scholar PubMed PubMed Central

18. Berube, D, Seralini, G, Gagne, R, Hammond, G. Localization of the human sex hormone-binding globulin gene (SHBG) to the short arm of chromosome 17 (17p12→ p13). Cytogenet Cell Genet 1990;54:65–7. https://doi.org/10.1159/000132958.Search in Google Scholar PubMed

19. Xita, N, Tsatsoulis, A. Genetic variants of sex hormone-binding globulin and their biological consequences. Mol Cell Endocrinol 2010;316:60–5. https://doi.org/10.1016/j.mce.2009.08.025.Search in Google Scholar PubMed

20. Fortunati, N, Catalano, MG, Boccuzzi, G, Frairia, R. Sex Hormone-Binding Globulin (SHBG), estradiol and breast cancer. Mol Cell Endocrinol 2010;316:86–92. https://doi.org/10.1016/j.mce.2009.09.012.Search in Google Scholar PubMed

21. Haiman, CA, Riley, SE, Freedman, ML, Setiawan, VW, Conti, DV, Le Marchand, L. Common genetic variation in the sex steroid hormone-binding globulin (SHBG) gene and circulating shbg levels among postmenopausal women: the Multiethnic Cohort. J Clin Endocrinol Metab 2005;90:2198–204. https://doi.org/10.1210/jc.2004-1417.Search in Google Scholar PubMed

22. Zhang, M, Hong, W, Wu, X, Zhang, Y, Li, F, Zhao, S-Q. A highly sensitive and direct competitive enzyme-linked immunosorbent assay for the detection of di-(2-ethylhexyl) phthalate (DEHP) in infant supplies. Anal Methods 2015;7:5441–6. https://doi.org/10.1039/c5ay00207a.Search in Google Scholar

23. Fong, JP, Lee, FJ, Lu, IS, Uang, SN, Lee, CC. Estimating the contribution of inhalation exposure to di-2-ethylhexyl phthalate (DEHP) for PVC production workers, using personal air sampling and urinary metabolite monitoring. Int J Hyg Environ Health 2014;217:102–9. https://doi.org/10.1016/j.ijheh.2013.04.002.Search in Google Scholar PubMed

24. Kim, H-Y. Risk assessment of di(2-ethylhexyl) phthalate in the workplace. Environ Health Toxicol 2016;31:e2016011-e. https://doi.org/10.5620/eht.e2016011.Search in Google Scholar PubMed PubMed Central

25. Chang, WH, Li, SS, Wu, MH, Pan, HA, Lee, CC. Phthalates might interfere with testicular function by reducing testosterone and insulin-like factor 3 levels. Hum Reprod (Oxf) 2015;30:2658–70. https://doi.org/10.1093/humrep/dev225.Search in Google Scholar PubMed

26. Hyun Kim, D, Min Choi, S, Soo Lim, D, Roh, T, Jun Kwack, S, Yoon, S, et al.. Risk assessment of endocrine disrupting phthalates and hormonal alterations in children and adolescents. J Toxicol Environ Health 2018;81:1150–64. https://doi.org/10.1080/15287394.2018.1543231.Search in Google Scholar PubMed

27. Fong, J-P, Lee, F-J, Lu, I-S, Uang, S-N, Lee, C-C. Relationship between urinary concentrations of di (2-ethylhexyl) phthalate (DEHP) metabolites and reproductive hormones in polyvinyl chloride production workers. Occup Environ Med 2015;72:346–53. https://doi.org/10.1136/oemed-2014-102532.Search in Google Scholar PubMed

28. Ge, R-S, Chen, G-R, Tanrikut, C, Hardy, MP. Phthalate ester toxicity in Leydig cells: developmental timing and dosage considerations. Reprod Toxicol 2007;23:366–73. https://doi.org/10.1016/j.reprotox.2006.12.006.Search in Google Scholar PubMed

29. Botelho, GG, Golin, M, Bufalo, AC, Morais, RN, Dalsenter, PR, Martino-Andrade, AJ. Reproductive effects of di (2-ethylhexyl) phthalate in immature male rats and its relation to cholesterol, testosterone, and thyroxin levels. Arch Environ Contam Toxicol 2009;57:777–84. https://doi.org/10.1007/s00244-009-9317-8.Search in Google Scholar PubMed

30. 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;30:313–21. https://doi.org/10.1016/j.reprotox.2010.04.005.Search in Google Scholar PubMed

31. Desdoits-Lethimonier, C, Albert, O, Le Bizec, B, Perdu, E, Zalko, D, Courant, F, et al.. Human testis steroidogenesis is inhibited by phthalates. Hum Reprod (Oxf) 2012;27:1451–9. https://doi.org/10.1093/humrep/des069.Search in Google Scholar

32. Pan, G, Hanaoka, T, Yoshimura, M, Zhang, S, Wang, P, Tsukino, H, et al.. 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 2006;114:1643–8. https://doi.org/10.1289/ehp.9016.Search in Google Scholar

33. Ye, T, Kang, M, Huang, Q, Fang, C, Chen, Y, Shen, H, et al.. Exposure to DEHP and MEHP from hatching to adulthood causes reproductive dysfunction and endocrine disruption in marine medaka (Oryzias melastigma). Aquat Toxicol 2014;146:115–26. https://doi.org/10.1016/j.aquatox.2013.10.025.Search in Google Scholar

34. Zhang, Y, Li, X, Gao, J, Wang, H. Influence of DEHP on thyroid, sex steroid‐related genes and gonadal differentiation in Rana chensinensis tadpoles. Environ Toxicol 2018;33:112–21. https://doi.org/10.1002/tox.22504.Search in Google Scholar

35. Hauser, R, Meeker, JD, Park, S, Silva, MJ, Calafat, AM. Temporal variability of urinary phthalate metabolite levels in men of reproductive age. Environ Health Perspect 2004;112:1734–40. https://doi.org/10.1289/ehp.7212.Search in Google Scholar

36. Jonsson, BA, Richthoff, J, Rylander, L, Giwercman, A, Hagmar, L. Urinary phthalate metabolites and biomarkers of reproductive function in young men. Epidemiology 2005;16:487–93. https://doi.org/10.1097/01.ede.0000164555.19041.01.Search in Google Scholar

37. Zhang, YH, Chen, BH, Zheng, LX, Wu, XY. Study on the level of phthalates in human biological samples. Zhonghua yu fang yi xue za zhi 2003;37:429–34.Search in Google Scholar

38. Thaler, MA, Seifert-Klauss, V, Luppa, PB. The biomarker sex hormone-binding globulin - from established applications to emerging trends in clinical medicine. Best Pract Res Clin Endocrinol Metabol 2015;29:749–60. https://doi.org/10.1016/j.beem.2015.06.005.Search in Google Scholar

39. Pasquali, R, Vicennati, V, Bertazzo, D, Casimirri, F, Pascal, G, Tortelli, O, et al.. Determinants of sex hormone-binding globulin blood concentrations in premenopausal and postmenopausal women with different estrogen status. Metab, Clin Exp 1997;46:5–9. https://doi.org/10.1016/s0026-0495(97)90159-1.Search in Google Scholar

40. Meeker, JD, Calafat, AM, Hauser, R. Urinary metabolites of di (2‐ethylhexyl) phthalate are associated with decreased steroid hormone levels in adult men. J Androl 2009;30:287–97. https://doi.org/10.2164/jandrol.108.006403.Search in Google Scholar PubMed PubMed Central

41. Cousin, P, Calemard-Michel, L, Lejeune, H, Raverot, G, Yessaad, N, Emptoz-Bonneton, A, et al.. Influence of SHBG gene pentanucleotide TAAAA repeat and D327N polymorphism on serum sex hormone-binding globulin concentration in hirsute women. J Clin Endocrinol Metab 2004;89:917–24. https://doi.org/10.1210/jc.2002-021553.Search in Google Scholar PubMed

42. Cui, Y, Shu, XO, Cai, Q, Jin, F, Cheng, JR, Cai, H, et al.. Association of breast cancer risk with a common functional polymorphism (Asp327Asn) in the sex hormone-binding globulin gene. Canc Epidemiol Biomarkers Prev 2005;14:1096–101. https://doi.org/10.1158/1055-9965.epi-04-0721.Search in Google Scholar PubMed

43. Hogeveen, KN, Cousin, P, Pugeat, M, Dewailly, D, Soudan, B, Hammond, GL. Human sex hormone-binding globulin variants associated with hyperandrogenism and ovarian dysfunction. J Clin Invest 2002;109:973–81. https://doi.org/10.1172/jci0214060.Search in Google Scholar

44. Dunning, AM, Dowsett, M, Healey, CS, Tee, L, Luben, RN, Folkerd, E, et al.. Polymorphisms associated with circulating sex hormone levels in postmenopausal women. J Natl Cancer Inst 2004;96:936–45. https://doi.org/10.1093/jnci/djh167.Search in Google Scholar PubMed

45. Li, Y, Fang, L, Yan, Y, Wang, Z, Wu, Z, Jia, Q, et al.. Association between human SHBG gene polymorphisms and risk of PCOS: a meta-analysis. Reprod Biomed Online 2020;42:227–36.10.1016/j.rbmo.2020.10.003Search in Google Scholar PubMed

Received: 2020-08-17
Accepted: 2021-01-02
Published Online: 2021-05-19

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 10.6.2024 from https://www.degruyter.com/document/doi/10.1515/jcim-2020-0329/html
Scroll to top button