Prepubertal exposure to commercial formulation of the herbicide glyphosate alters testosterone levels and testicular morphology

Abstract

Glyphosate is a herbicide widely used to kill weeds both in agricultural and non-agricultural landscapes. Its reproductive toxicity is related to the inhibition of a StAR protein and an aromatase enzyme, which causes an in vitro reduction in testosterone and estradiol synthesis. Studies in vivo about this herbicide effects in prepubertal Wistar rats reproductive development were not performed at this moment. Evaluations included the progression of puberty, body development, the hormonal production of testosterone, estradiol and corticosterone, and the morphology of the testis. Results showed that the herbicide (1) significantly changed the progression of puberty in a dose-dependent manner; (2) reduced the testosterone production, in semineferous tubules’ morphology, decreased significantly the epithelium height (P < 0.001; control = 85.8 ± 2.8 μm; 5 mg/kg = 71.9 ± 5.3 μm; 50 mg/kg = 69.1 ± 1.7 μm; 250 mg/kg = 65.2 ± 1.3 μm) and increased the luminal diameter (P < 0.01; control = 94.0 ± 5.7 μm; 5 mg/kg = 116.6 ± 6.6 μm; 50 mg/kg = 114.3 ± 3.1 μm; 250 mg/kg = 130.3 ± 4.8 μm); (4) no difference in tubular diameter was observed; and (5) relative to the controls, no differences in serum corticosterone or estradiol levels were detected, but the concentrations of testosterone serum were lower in all treated groups (P < 0.001; control = 154.5 ± 12.9 ng/dL; 5 mg/kg = 108.6 ± 19.6 ng/dL; 50 mg/dL = 84.5 ± 12.2 ng/dL; 250 mg/kg = 76.9 ± 14.2 ng/dL). These results suggest that commercial formulation of glyphosate is a potent endocrine disruptor in vivo, causing disturbances in the reproductive development of rats when the exposure was performed during the puberty period.

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References

  1. Abreu CH Jr, Muraoka T, Lavorante AF (2003) Relationship between acidity and chemicals properties of Brazilian soils. Sci Agric 60:337–343

    CAS  Google Scholar 

  2. Akingbemi BT (2005) Estrogen regulation of testicular function. Reprod Biol Endocrinol 3:1–13

    Article  CAS  Google Scholar 

  3. Atanassova NN, Walker M, McKinnel C, Fisher JS, Sharpe RM (2005) Evidence that androgens and oestrogens, as well follicle stimulating hormone, can alter Sertoli cell number in the neonatal rat. J Endocrinol 184:107–117

    Article  CAS  PubMed  Google Scholar 

  4. Benachour N, Sipahutar H, Moslemi S, Gasnier C, Travert C, Seralini GE (2007) Time and dose-dependent effects of Roundup on human embryonic and placental cells. Arch Environ Contam Toxicol 53:126–133

    Article  CAS  PubMed  Google Scholar 

  5. Benedetti AL, Vituri CD, Trentin AG, Domingues MAC, Alvarez-Silva M (2004) The effects of sub-chronic exposure of Wistar rats to the herbicide Glyphosate-Biocarb. Toxicol Lett 153:227–232

    Article  CAS  PubMed  Google Scholar 

  6. Brausch JM, Smith PN (2007) Toxicity of three polyethoxylated tallowamine surfactant formulations to laboratory and field collected fairy shrimp, Thamnocephalus platyurus. Arch Environ Contam Toxicol 52:217–221

    Article  CAS  PubMed  Google Scholar 

  7. Caron KM, Soo SC, Wetsel WC, Stocco DM, Clark BJ, Parker KL (1997) Target disruption of the mouse gene encoding esteroidogenic acute regulatory protein provides insights into congenital lipoid adrenal hyperplasia. Proc Natl Acad Sci USA 94:11540–11545

    Article  CAS  PubMed  Google Scholar 

  8. Cerdeira AL, Gazziero DLP, Duke SO, Matallo MB, Spadotto CA (2007) Review of potential environmental impacts of transgenic glyphosato-resistent soybean in Brazil. J Environ Sci Health B 42:539–549

    Article  CAS  PubMed  Google Scholar 

  9. Clementi M, Tiboni GM, Causin R, Rocca CL, Maranghi F, Raffagnato F, Tenconi R (2008) Pesticides and fertility: an epidemiological study in Northeast Italy and review of the literature. Reprod Toxicol 26:13–18

    Article  CAS  PubMed  Google Scholar 

  10. Colborn T, Dumanoski D, Meyers JP (1996) Our stolen future: are we threatening our fertility, intelligence and survival? A scientific detective story. Ed Dutton, New York

    Google Scholar 

  11. Cox C, Surgan M (2006) Unidentified inert ingredients in pesticides: implications for human and environmental health. Environ Health Perspect 114:1803–1806

    CAS  PubMed  Google Scholar 

  12. Curwin BD, Hein MJ, Sanderson WT, Nishioka MG, Reynolds SJ, Warm EM, Alavanja MC (2005) Pesticide contamination inside farm and nonfarm homes. J Occup Environ Hyg 2:357–367

    Article  CAS  PubMed  Google Scholar 

  13. Curwin BD, Hein MJ, Nishioka SandersonWT, MG ReynoldsSJ, Warm EM, Alavanja MC (2007) Urinary pesticide concentrations among children, mothers and fathers living in farm and non-farm households in Iowa. J Occup Environ Hyg 51:53–55

    CAS  Google Scholar 

  14. Dallegrave E, Mantese FD, Oliveira RT, Andrade AJ, Dalsenter PR, Langeloh A (2007) Pre- and postnatal toxicity of the commercial glyphosate formulation in Wistar rats. Arch Toxicol 81(9):665–673

    Article  CAS  PubMed  Google Scholar 

  15. Epand RM (2006) Cholesterol interactions of proteins with membrane domains. Prog Lipid Res 45:279–294

    Article  CAS  PubMed  Google Scholar 

  16. FAO and WHO (2004) Pesticides residues in food. Toxicological evaluations. Available via http://www.who.int/ipcs/publications/jmrp/draft_impr_2004_monograph.pdf. Accessed 14 July 2007

  17. Foster WG, Neal MS, Han MS, Dominguez MM (2008) Environmental contaminants and human infertility: hypothesis or cause for concern? J Toxicol Environ Health 11:162–176

    Article  CAS  Google Scholar 

  18. Getenga ZM, Kengara FO (2004) Mineralization of glifosate in compost-amended soil under control conditions. Bull Environ Contam Toxicol 72:266–275

    Article  CAS  PubMed  Google Scholar 

  19. Goldsborough LG, Brown DJ (1993) Dissipation of glyphosate and aminomethylphosphonic acid in water and sediments of boreal forest. Environ Toxicol Chem 12:1139–1147

    CAS  Article  Google Scholar 

  20. Goyal HO, Robateou A, Braden TD, Williams CS, Srivastava KK, Ali K (2003) Neonatal estrogen exposure of male rats alters reproductive functions at adulthood. Biol Reprod 68:2081–2091

    Article  CAS  PubMed  Google Scholar 

  21. Hafez ESE, Hafez B (2000) Reproduction in farm animals. Ed Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  22. Haney RL, Senseman SA, Hons FM (2002) Bioremediation and biodegradation: effect of Roundup ultra on microbial activity and biomass from selected soils. J Environ Qual 31:730–735

    CAS  PubMed  Google Scholar 

  23. Hayes WJ, Laws ER (1991) Handbook of pesticide toxicology. Academic Press, San Diego

    Google Scholar 

  24. Lu FC (1995) A review of the acceptable daily intakes of pesticides assessed by WHO. Regul Toxicol Pharmacol 21:352–364

    Article  CAS  PubMed  Google Scholar 

  25. Marc J, Mulner-Lorillon O, Boulben S, Hureau D, Durand G, Bellé R (2002) Pesticide Roundup provokes cell division dysfunction at the level of CDK1/cyclin B activation. Chem Res Toxicol 15:326–331

    Article  CAS  PubMed  Google Scholar 

  26. Norman AW, Litwack G (1997) Hormones. Academic Press, California

    Google Scholar 

  27. Ojeda SR, Urbanski HF (1994) Puberty in the rat. In: Knobil E, Neill JD (eds) The physiology of reproduction. Raven Press, New York

    Google Scholar 

  28. Oliveira AG, Telles LF, Hess RA, Mahecha GAB, Oliveira CA (2007) Effects of the herbicide Roundup on the epididymal region of drakes Anas platyrhynchos. Reprod Toxicol 23:182–191

    Article  CAS  PubMed  Google Scholar 

  29. Parker RM (2006) Testing for reproductive toxicity. In: Hood RD (ed) Developmental and reproductive toxicology. Taylor and Francis, New York

    Google Scholar 

  30. Peixoto F (2005) Comparative effects of the Roundup and glyphosate on mitochondrial oxidative phosphorylation. Chemosphere 61:1115–1122

    Article  CAS  PubMed  Google Scholar 

  31. Richard S, Moslemi S, Sipahutar H, Benachour N, Seralini G (2005) Differential effects of glyphosate and Roundup on human placental cells. Environ Health Perspect 113:716–720

    CAS  PubMed  Google Scholar 

  32. Roeleveld N, Bretveld R (2008) The impact of pesticides on male fertility. Curr Opin Obstet Gynecol 20:229–233

    Article  PubMed  Google Scholar 

  33. Romano RM, Romano MA, Moura MO, Oliveira CA (2008) A exposição ao glifosato-Roundup causa atraso no início da puberdade em ratos machos. Braz J Vet Res Anim Sci 45:481–487

    Google Scholar 

  34. Scott FG (2005) Developmental biology. London: Ed Sinauer. Available via http://www.ncbi.nlm.nih.gov. Accessed 14 Oct 2008

  35. Silva MD, Peralba MCR, Mattos MLT (2003) Determinação do glifosato e ácido aminometilfosfônico em águas superficiais do Arroio Passo do Pilão. Pest: Ecotox e Meio Amb 13:19–28

    Google Scholar 

  36. Solomon GM, Schettler T (2000) Environment and health: endocrine disruption and potential human health implications. Can Med Assoc J 163:1471–1476

    CAS  Google Scholar 

  37. Stoker TE, Parks LG, Gray LE, Cooper RL (2000) Endocrine-disrupting chemicals: pubertal exposures and effects on sexual maturation and thyroid function in the male rat. A focus on the EDSTAC recommendations. Endocrine disrupting screening and testing advisory committee. Crit Rev Toxicol 30:197–252

    Article  CAS  PubMed  Google Scholar 

  38. Tsui MTK, Chu LM (2003) Aquatic toxicity of glyphosate-base formulations: comparison between different organisms and the effects of environmental factors. Chemosphere 52:1189–1197

    Article  CAS  PubMed  Google Scholar 

  39. Walsh LP, McCormick C, Martin C, Stocco DM (2000) Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory (StAR) protein expression. Environ Health Perspect 108:769–776

    Article  CAS  PubMed  Google Scholar 

  40. Williams GM, Kroes R, Munro IC (2000) Safety evaluation and risk assessment of the herbicide Roundup and its active ingredient, glyphosate, for humans. Regul Toxicol Pharmacol 31:117–165

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank the Brazilian National Council of Scientific and Technological Development for financial support of this research (Edital MCT/CNPq 02/2006-Universal/process 471651/2006-0), the CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for scholarship.

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Correspondence to R. M. Romano.

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Romano, R.M., Romano, M.A., Bernardi, M.M. et al. Prepubertal exposure to commercial formulation of the herbicide glyphosate alters testosterone levels and testicular morphology. Arch Toxicol 84, 309–317 (2010). https://doi.org/10.1007/s00204-009-0494-z

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Keywords

  • Glyphosate
  • Roundup
  • Endocrine disruption
  • Prepubertal exposure
  • Testosterone
  • Testicular morphology