Skip to main content

Advertisement

Log in

Low doses of chlorpyrifos interfere with spermatogenesis of rats through reduction of sex hormones

  • Research Article
  • Published:
Environmental Science and Pollution Research Aims and scope Submit manuscript

Abstract

Use of pesticides results in indirect effects on human health. We aimed to evaluate implications of toxicological effects of subchronic chlorpyrifos exposure on reproductive function in male rats. A total of 48 adult Wistar male rats were separated into four groups (n = 12). Animals were gavaged with 2.5 mg/kg (T1), 5 mg/kg (T2), or 10 mg/kg (T3) body weight of chlorpyrifos (CPF) or distilled water (control) daily for 30 days. Organ weights, epididymal sperm parameters, DNA integrity, sex hormonal (FHS and LH) levels, and alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), and creatinine concentrations were determined on day 31. Another two sets of (four groups/set; n = 10) animals were orally treated with the same doses of CPF, control animal groups were treated with distilled water only for 30 days, and fertility indices and blood plasma acetylcholine esterase (AchE) were determined on day 31. Exposure to CPF resulted in a significant (p < 0.05) decrease in weights of testis and epididymis. An increase in liver weight resulted in reduced sperm counts and sperm motility and an increase in sperm abnormalities. Significant reduction in serum testosterone (p < 0.01), luteinizing hormone (p < 0.05), and follicular stimulating hormone (p < 0.05) levels was evident in animals treated with the highest dose. A significant decrease in the number of viable implantation sites and pups was observed in female rats mated with the T3 (p < 0.01) and T2 (p < 0.05) males. The ALT, AST, GGT, and creatinine contents were significantly increased (p < 0.05 and p < 0.01, respectively) on CPF exposure. A significant (p < 0.01) reduction in blood plasma AchE enzyme was observed with the highest dose. Our results demonstrated that prolonged exposure of CPF induces spermatogenesis damage, possibly through interference with sex hormones and AchE enzyme resulting in reduction of fertility. Therefore, awareness programs on handling CPF (pesticides) to enhance safety warrant minimization of its hazards.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Arena ACDB, Fernandez EM, Porto DZ, Bissacot OCM, Pereira G, Wilma WG (2008) Fenvalerate, a pyrethroid insecticide, adversely affects sperm production, and storage in male rats. J Toxicol Environ Health 71:1550–1558. doi:10.1080/15287390802392024

    Article  CAS  Google Scholar 

  • Brandit C, Burnett DC, Arcinas L, Palace V, Anderson WG (2015) Effects of chlorpyrifos on in vitro sex steroid production and thyroid follicular development in adult and larval Lake Sturgeon, Acipenser fulvescens. Chemosphere 132:179–187. doi:10.1016/j.chemosphere.2015.03.031

    Article  Google Scholar 

  • Chang WJ, Joe KT, Park HY, Jeong JD, Lee DK (2013) The relationship of liver function tests to mixed exposure to lead and organic solvents. Ann Occup Environ Med 25:5. doi:10.1186/2052-4374-25-5

  • Colborn T, vom Saal FS, Soto AM (1993) Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ Health Perspect 101:378–384

    Article  CAS  Google Scholar 

  • Cole TB, Bever RP, Bammeir TK, Park SS, Farin FM, Costa LG, Furlong CE (2011) Repeated developmental exposure of mice to chlorpyrifos oxon is associated with paraoxonase 1 (PON1)-modulated effects on cerebellar gene expression. Toxicol Sci 123:155–169. doi:10.1093/toxsci/kfr157

    Article  CAS  Google Scholar 

  • Deb N, Das S (2013) Chlorpyrifos toxicity in fish: a review. Curr World Environ 8:174–184. doi:10.12944/CWE.8.1.17

    Article  Google Scholar 

  • De Silva PMC, Pathiratne A, van Straalen MN, van Gastel CAM (2010) Chlorpyrifos causes decreased organic matter decomposition by supressing earthworm and termite communities in tropical soil. Env Poll 151: 3041–3047. doi:10.1016/j.envpol.2010.06.032

  • Dinham B (2005) Prolonged exposure to some agricultural pesticides may increase the risk of lung cancer in agricultural workers. Evidence-Based Heal Public Heal 9:203–205. doi:10.1016/j.ehbc.2005.03.029

    Article  Google Scholar 

  • Dutta AL, Sahu CR (2013) Emblica officinalis Garten fruits extract ameliorates reproductive injury and oxidative testicular toxicity induced by chlorpyrifos in male rats. Springerplus 2:541. doi:10.1186/2193-1801-2-541

  • Elsharkawy EE, Yahia D, El-Nisr NA (2014) Chlorpyrifos induced testicular damage in rats: ameliorative effect of glutathione antioxidant. Environ Toxicol 29:1011–1019. doi:10.1002/tox.21831

    Article  CAS  Google Scholar 

  • Farag FT, Radwan HA, Sorour F, Okazy AE, El-Agamy E, El-Sebae AE (2010) Chlorpyrifos induced reproductive toxicity in male mice. Repord Toxicol 25:80–85. doi:10.1016/j.reprotox.2009.10.003

    Article  Google Scholar 

  • Fattahi E, Jorsaraei SGA, Gardaneh M (2012) The effect of Carbaryl on pituitary gonadal axis of male rats. Int J Reprod Med 10:419–424. doi:10.1080/02772248.2012.693493

    CAS  Google Scholar 

  • Gadella BM (2014) Sperm preparation for fertilization. In: Chenoweth P, Lorton S (eds) Animal andrology: theories and applications. CABI, Bostorn, pp 57–75

    Chapter  Google Scholar 

  • Guido C, Santoro M, Amicis FD, Perrotta I, Panza S, Rago V, Cesario GM, Lanzeano M, Aquilla S (2014) Human sperm anatomy and endocrinology in varicocele: role of androgen receptor. Reproduction 147:589–598. doi:10.1530/REP-13-0542

    Article  CAS  Google Scholar 

  • Gupta RS, Yadav VP, Dixit VP, Dobhal MP (2001) Antifertility studies of Colebrookia oppositifolia leaf extract in male rats with special reference to testicular cell population dynamics. Fitoterapia 72:236–245. doi:10.1016/S0367-326X(00)00311-7

    Article  CAS  Google Scholar 

  • Heikal TM, Mossa AH, Ibrahim AW, Abdel-Hamid HF (2014) Oxidative damage and reproductive toxicity associated with cyromazine and chlorpyrifos in male rats: The protective effects of green tea extract. Research J Env Toxicol 8:53–67. doi.10.3923/rjet.2014.53.67

  • Ijiri TW, Vadnais ML, Huang AP, Lin AM, Levin LR, Buck J, Gerton GL (2014) Thiol changes during epididymal maturation: a link to flagella angulation in mouse spermatozoa? Andrology 2:65–75. doi:10.1111/j.2047-2927.2013.00147

    Article  CAS  Google Scholar 

  • Joshi SC, Mathur R, Gulati N (2007) Testicular toxicity of chlorpyrifos (an organophosphate insecticide) in albino rats. Toxicol Indus Health 23:423–444. doi:10.1177/0748233707080908

    Article  Google Scholar 

  • Karanth S, Liu J, Oliver K, Pope C (2004) Interactive toxicity of the organophosphorus insecticides chlorpyriphos and methyl parathion in rats. Toxicol Appl Pharmacol 196:183–190. doi:10.1016/j.taap.2009.02.022

    Article  CAS  Google Scholar 

  • Khokhar JY, Tyndale RF (2012) Rat brain CYP2B-enzymatic activation of chlorpyrifos to the oxon mediates cholinergic neurotoxicity. Toxicol Sci 126:325–335. doi:10.1093/toxsci/kfs029

    Article  CAS  Google Scholar 

  • Kim WR, Flamm SL, Bisceglie MD, Bodenheimer HC (2008) Serum activity of alanine aminotransferase (ALT) as indicator of health and disease. Hepatology 47:1363–1370. doi:10.1002/hep.22109

    Article  CAS  Google Scholar 

  • Lehrer RI, Wuyuan L (2012) œ-Defensins in human innate immunity. Immunol Rev 245:84–112. doi:10.1111/j.1600-065X.2011.01082

    Article  CAS  Google Scholar 

  • Lotti M (1991) Treatment of acute organophosphate poisoning. Med J Aust 154:51–55

    CAS  Google Scholar 

  • Lucio RA, Tlcahi-Lopez JL, Eguibar JR, Amgo A (2013) Sperm count and motility decrease in old rats. Physiol Behav 110-111:73–79. doi:10.1016/j.physbeh.2012.12.015

    Article  CAS  Google Scholar 

  • Mandal TK, Das NS (2011) Correlation of testicular toxicity and oxidative stress induced by chlorpyrifos in rats. Hum Exp Toxicol 30:1529–1539. doi:10.1177/0960327110392400

    Article  CAS  Google Scholar 

  • Mansour SA, Mossa AH (2010) Oxidative damage, biochemical and histopathological alteration in rat exposed to chlorpyrifos and the role of zinc as antioxidant. Pest Biochem Physiol 96:14–23. doi:10.1016/j.pestbp.2009.08.008

    Article  CAS  Google Scholar 

  • Marasinghe J, Quming Y, Connell D (2014) Assessment of health risk in human populations due to chlorpyrifos. Toxics 2:92–114. doi:10.3390/toxics2020092

    Article  CAS  Google Scholar 

  • Menike AMW et al (2012) Chlorpyrifos contamination of fresh water in a commercial vegetable cultivation area in Sri Lanka and factors affecting contamination. J. Natl. Sci. Found. Sri Lanka 40(4):333–344. doi:10.4038/jnsfsr.v40i4.5047

    CAS  Google Scholar 

  • Moline JM, Golden AL, Bar-Chama N, Smith E, Rauch ME, Chapin RE, Perreault SD, Schrader SM, Suk WA, Landrigan PJ (2008) Exposure to hazardous substances and male reproductive health: a research framework. Environ Heal Prospect 108:803–813. doi:10.1289/ehp.00108803

    Article  Google Scholar 

  • Mossa AH, Abbassy MA (2012) Adverse haematological and biochemical effects of certain formulated insecticides in male rats. Res Environ Toxicol 6:160–168. doi:10.3923/rjet.2012.160.168

    Article  Google Scholar 

  • Mossa AH, Swelam ES, Mohafrash SMM (2015) Sub-chronic exposure to fipronil induced oxidative stress, biochemical and histopathological changes in the liver and kidney of male albino rats. Toxicol Rep 2:775–777. doi:10.1016/j.toxrep.2015.02.009

    Article  CAS  Google Scholar 

  • Muangphra P, Tharapoom K, Euawong N, Namchote S, Gooneratne R (2015) Chronic toxicity of commercial chlorpyrifos to earthworm Pheretima peguana. Envrion Toxicol. doi:10.1002/tox.22150

  • Pakarainen T, Zhang F, Mäkelä S, Poutanen M, Huhtaniemi I (2005) Testosterone replacement therapy induces spermatogenesis and partially restores fertility in luteinizing hormone receptor knockout mice. Endocrinol 146:2–606. doi:10.1210/en.2004-0913

    Article  Google Scholar 

  • Panuwet P, Prapamontol T, Chantara S, Barr DB (2008) Concentration of urinary pesticide metabolites in small-scale farmers in Chiang Mai Province, Thailand. Sci Total Env 407:655–668. doi:10.1016/j.scitotenv.2008.08.044

    Article  CAS  Google Scholar 

  • Peiris LDC, Moore HDM (2001a) Effects of acute and chronic doses of methoxy acetic acid on hamster sperm fertilizing ability. Asian J Androl 3:209–221 http://www.asiaandro.com/archive/1008-682x/3/209.htm

    CAS  Google Scholar 

  • Peiris LDC, Moore HDM (2001b) Evaluation of effects of 1,3-dinitrobenzene on sperm motility of hamster using computer assisted semen analysis (CASA). Asian J Androl 3:109–114

    CAS  Google Scholar 

  • Peiris LDC, Ratnasooriya WD, Jayatunga YNA (1995) Antireproductive effects of male rats exposed to Methamidophos. Ceylon J Sci (Bio Sci) 24:53–59. doi:10.1289/ehp.1510385

    Google Scholar 

  • Peiris-John RJ, Wickremasinghe R (2008) Impact of low-level exposure to organophosphates on human reproduction and survival. Trans R Soc Trop Med Hyg 2008:239–245. doi:10.1016/j.trstmh.2007.11.012

    Article  Google Scholar 

  • Phung DT, Connell D, Miller G, Chu C (2012) Probabilistic assessment of chlorpyrifos exposure to rice farmers in Viet Nam. J Expo Sci Environ Epidemiol 22:417–423. doi:10.1038/jes.2012.32

    Article  CAS  Google Scholar 

  • Plant TM, Marshall GR (2001) The functional significance of FSH in spermatogenesis and the control of its secretion in male primates. Endocrion Rev 22:764–786. doi:10.1111/j.1365-2605.2007.00853

    Article  CAS  Google Scholar 

  • Rahman MS, Lee JS, Kwon WS, Pang MG (2013) Sperm proteomics: road to male fertility and contraception. Int J Endocrinol 2013:360986. doi:10.1155/2013/360986

  • Raj MV, Selvakumar K, Krishnamoorthy G, Revathy S, Elumal P, Arunakaran J (2014) Impact of lycopene on epididymal androgen and estrogen receptors’ expression in polychlorinated biphenyls–exposed rat. Reprod Biol 21:89–101. doi:10.1177/1933719113492213

    Google Scholar 

  • Ratnasooriya WD, Jayatunga YNA, Peiris LDC (1996) Monocrotophos impairs the fertility of male rats. Med Sci Res 24:403–406. doi:10.3742/OPEM.2007.7.3.304

    CAS  Google Scholar 

  • Rauh VA, Perera FP, Horton MK, Whyatt RM, Bansal R, Hao X, Liu J, Barr DB, Slotkin TA, Peterson BS (2012) Brain anomalies in children exposed prenatally to a common organophosphate pesticide. Proc Natl Acad Sci U S A 109:7871–7876. doi:10.1073/pnas.1203396109

    Article  CAS  Google Scholar 

  • Sai L, Li X, Liu Y, Guo Q, Xie L, Yu G, Bo C, Zhang Z, Li L (2014) Effects of chlorpyrifos on reproductive toxicology of male rats. Environ Toxicol 29:1083–1888. doi:10.1002/tox.21838.Epub 2013

    Article  CAS  Google Scholar 

  • Salazar-Arredondo E, de Jesus S-HM, Rojas-Garcia E, Hernandez-Ochoa I, Quintanilla-Vega B (2008) Sperm chromatin alteration and DNA damage by methyl-parathion, chlorpyrifos and diazinon and their oxon metabolites in human spermatozoa. Reprod Toxicol 25:455–460. doi:10.1016/j.reprotox.2008.05.055

    Article  CAS  Google Scholar 

  • Selvarajah A, Thiruchelvam S (2007) Factors affecting pesticide use by farmers in Vavuniya District. Trop Agric Res 19:380–388 http://dl.nsf.ac.lk/handle/1/11744

    Google Scholar 

  • Sengaputta P, Banergee R (2014) Environmental toxins alarming impacts of pesticides on male fertility. Hum Exp Toxicol 33:1017–1039

    Article  Google Scholar 

  • Shekish TJ, Patel BJ, Joshi DV, Patel RB, Jegoda MD (2013) Repeated dose oral toxicity of inorganic mercury in wistar rats: biochemical and morphological alterations. Vet Worl 6:563–567. doi:10.5455/vetworld.2013.563-567

    Article  Google Scholar 

  • Shittu M, Ayo JO, Ambali SF, Fatihu MY, Onyeanusi BI, Kawu MU (2012) Chronic chlorpyrifos-induced oxidative changes in the testes and pituitary gland of wistar rats: ameliorative effects of vitamin C. Pestic Biochem Physiol 102:79–85. doi:10.1016/j.pestbp.2011.10.014

    Article  CAS  Google Scholar 

  • Shittu M, Ambali SF, Ayo JO, Faithu MY, Sulaiman MM, Yaqub LS (2013) Evaluation of chronic chlorpyrifos-induced reproductive toxicity in male Wistar rat: protective effects of vitamin C. J Exp Integ Med 3:23–30. doi:10.5455/jeim.041012.or.047

    Article  Google Scholar 

  • Silmen S, Saloua EF, Najoua FG (2014) Oxidative stress and cytotoxic potential of acetyl cholinesterase insecticide, malathion in reproductive toxicology of male adolescent mice after acute exposure. Iran J Basic Med Sci 17:522–530 doi:

    Google Scholar 

  • Sivayoganathan C, Gnanachandran S, Lewis J, Fernando M (1995) Protective measure use and symptoms among agro pesticide applicators in Sri Lanka. Soc Sci Med 2:431–436. doi:10.1016/0277-9536(94)00143-H

    Article  Google Scholar 

  • Ten J, Mendiola J, Torres-Cantero AM, Moreno-Grau JM, Moreno-Grau S, Roca M, Romero J et al (2008) Occupational and lifestyle exposures on male infertility: a mini review. The Open Reprod Sci J 1:16–21

    Article  CAS  Google Scholar 

  • Tian Y, Ishikawa H, Yamaguchi T, Yamauchi T, Yokoyamab K (2005) Teratogenicity and developmental toxicity of CPF, maternal exposure during organogenesis in mice. Reprod Toxicol 20:267–271. doi:10.1016/j.reprotox.2005.01.012

    Article  CAS  Google Scholar 

  • Timofeeva OA, Gordon CJ (2001) Changes in EEG power spectra and behavioral states in rats exposed to the acetylcholinesterase inhibitor chlorpyrifos and muscarinic agonist oxotremorine. Brain Res 893:165–177

    Article  CAS  Google Scholar 

  • Usmani KA, Hodgson E, Rose RL (2004) In vitro metabolism of carbofuran by human, mouse, and rat cytochrome P450 and interactions with chlorpyrifos, testosterone, and estradiol. Chem Biol Interact 150:221–232. doi:10.1016/j.cbi.2004.09.015

    Article  CAS  Google Scholar 

  • Van Der Hoek W, Konradsen F, Athukorala K, Wanigadewa T (1998) Pesticide poisoning: a major health problem in Sri Lanka. Soc Sci Med 46:495–504. doi:10.1016/S0277-9536(97)00193-7

    Article  Google Scholar 

  • Yen J, Donerly S, Levin ED, Linney EA (2011) Differential acetylcholinesterase inhibition of chlorpyrifos, diazinon and parathion in larval zebrafish. Neurotoxicol Teratoly 33:735–741. doi:10.1016/j.ntt.2011.10.004

    Article  CAS  Google Scholar 

  • Zafar MI, Van Wijngaarden RP, Roessink I, Van den Brink PJ (2011) Effects of time-variable exposure regimes of the insecticide chlorpyrifos on freshwater invertebrate communities in microcosms. Envrion Toxicol Chem 30:1383–1394. doi:10.1002/etc.509

    Article  CAS  Google Scholar 

  • Zidan NA (2009) Evaluation of the reproductive toxicity of chlorpyrifos methyl, diazinon and profenofos pesticides in male rats. Int J Pharmacol 5:51–57. doi:10.3923/ijp.2009.51.57

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dinithi Champika Peiris.

Ethics declarations

The animal experiment was performed as per committee for the purpose of control and supervision of experiments on animal norms after obtaining the institutional animal ethics committee clearance (ethical no: 25/16).

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Additional information

Responsible editor: Philippe Garrigues

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Peiris, D.C., Dhanushka, T. Low doses of chlorpyrifos interfere with spermatogenesis of rats through reduction of sex hormones. Environ Sci Pollut Res 24, 20859–20867 (2017). https://doi.org/10.1007/s11356-017-9617-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-017-9617-x

Keywords

Navigation