Skip to main content

Advertisement

Log in

Repeated exposure of pyriproxyfen to pregnant female mice causes developmental abnormalities in prenatal pups

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

Abstract

The continuous exposure to conventional pesticides leads to severe health and environmental issues especially at prenatal stage during developmental period. Herein, we aimed to investigate the anomalies due to repeated exposure of pyriproxyfen in pregnant female mice and their neonates. Twenty-four pregnant female mice were repeatedly administered with pyriproxyfen at 30, 100, 300, and 1000 mg/kg by oral gauge from gestation day (GD) 7 to gestation day 17 and six females were given distilled water in the control group. All the live pups were euthanized at postnatal day (PND) 7 and their organs (heart, liver, kidney, and brain) were dissected out, weighed, and assessed for further histopathological examinations. The results exhibited a significant (P < 0.001) decrease in the body weight gain of all treated pregnant mice in comparison to the controls and a significant increase in the gestational length was observed in group IV (P < 0.01) and group V (P < 0.001). In addition, no live pups were born in groups IV and V and one pregnant female mouse was also found dead in both treatments. The body weights of the pups were significantly decreased in group II (P < 0.05) and group III (P < 0.001) and the relative organ (liver, heart, and kidney) weight of the pups was increased significantly (P < 0.001, P < 0.01, P < 0.05) due to prenatal exposure in group II as compared to group I. The relative brain weights of the pups were decreased significantly (P < 0.001) in groups II and III as compared to group I. The liver, kidney, heart, and brain sections exhibited various histological alterations in groups II and III by hematoxylin and eosin staining. Furthermore, immunohistochemical staining of the coronal sections of pup’s brain showed significant (P < 0.001) reduction in cortical radial thickness and total neural count in group II and III as compared to group I. Therefore, the prenatal exposure to pyriproxyfen provoked the damage to various organs in mice offspring and an increase in fetal death at higher doses.

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
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Abou-Amer WL, Ali FA, Rady MI, El.Abdelmonem A (2010) Teratogenic effects induced by three pesticides in pregnant rats. Alex J Pharm Sci 24:21–26

    CAS  Google Scholar 

  • Adjrah Y, Simplice DK, Agbonon A, Ameyapoh Y, de Souza C, Gbeassor M (2013) Effect of cypermethrin-treated lettuce (Lactuca sativa) on Wistar rat liver. J Appl Pharm Sci 3:128–132

    Google Scholar 

  • Albuquerque MF, Souza WV, Mendes AD, Lyra TM, Ximenes RA, Araújo TV, Braga C, Miranda-Filho DB, Martelli CM, Rodrigues LC (2016) Pyriproxyfen and the microcephaly epidemic in Brazil - an ecological approach to explore the hypothesis of their association. Mem Inst Oswaldo Cruz 111(12):774–776

    Google Scholar 

  • Bali YA, Ba-Mhamed S, Bennis M (2017) Behavioral and immunohistochemical study of the effects of subchronic and chronic exposure to glyphosate in mice. Front Behav Neurosci 11:146

    Google Scholar 

  • Barros AL, Cavalheiro GF, Souza AV, Traesel GK, Anselmo-Franci JA, Kassuya CA, Arena AC (2016) Subacute toxicity assessment of diflubenzuron, an insect growth regulator, in adult male rats. Environ Toxicol 31(4):407–414

    Google Scholar 

  • Bishop HI, Cobb MM, Kirmiz M, Parajuli LK, Mandikian D, Philp AM, Melnik M, Kuja-Panula J, Rauvala H, Shigemoto R, Murray KD (2018) Kv2 ion channels determine the expression and localization of the associated AMIGO-1 cell adhesion molecule in adult brain neurons. Front Mol Neurosci 11:1

    Google Scholar 

  • Bonvallot N, Canlet C, Blas-Y-Estrada F, Gautier R, Tremblay-Franco M, Chevolleau S, Cordier S, Cravedi J (2017) Metabolome disruption of pregnant rats and their offspring resulting from repeated exposure to a pesticide mixture representative of environmental contamination in Brittany. PLoS One 13:e0198448

    Google Scholar 

  • Bouchard MF, Bellinger DC, Wright RO, Weisskopf MG (2010) Attention-deficit/hyperactivity disorder and urinary metabolites of organophosphate pesticides. Pediatrics 125(6):1270–1277

    Google Scholar 

  • Bretveld RW, Thomas CM, Scheepers PT, Zielhuis GA, Roeleveld N (2006) Pesticide exposure: the hormonal function of the female reproductive system disrupted? Reprod Biol Endocrinol 4:30

    Google Scholar 

  • Burke RD, Todd SW, Lumsden E, Mullins RJ, Mamczarz J, Fawcett WP, Gullapalli RP, Randall WR, Pereira EFR, Albuquerque EX (2017) Developmental neurotoxicity of the organophosphorus insecticide chlorpyrifos: from clinical findings to preclinical models and potential mechanisms. J Neurochem 142(Suppl 2):162–177

    CAS  Google Scholar 

  • Cole TB, Fishera JC, Burbachera TM, Costaa TM, Furlong CE (2012) Neurobehavioral assessment of mice following repeated postnatal exposure to chlorpyrifos-oxon. Neurotoxicol Teratol 34:311–322

    CAS  Google Scholar 

  • Engel LS, O’Meara ES, Schwartz SM (2000) Maternal occupation in agriculture and risk of limb defects in Washington State, 1980-1993. Scand J Work Environ Health 26(3):193–198

    CAS  Google Scholar 

  • Engel SM, Wetmur J, Chen J, Zhu C, Barr DB, Canfield RL, Wolff MS (2011) Prenatal exposure to organophosphates, paraoxonase 1, and cognitive development in childhood. Environ Health Perspect 119:1182–1188

    Google Scholar 

  • Eskenazi B, Harley K, Bradman A, Weltzien E, Jewell NP, Barr DB, Furlong CE, Holland NT (2004) Association of in utero organophosphate pesticide exposure and fetal growth and length of gestation in an agricultural population. Environ Health Perspect 112:1116–1124

    CAS  Google Scholar 

  • Eskenazi B, Marks AR, Bradman A, Harley K, Barr DB, Johnson C, Morga N, Jewell NP (2007) Organophosphate pesticide exposure and neurodevelopment in young Mexican-American children. Environ Health Perspect 115:792–798

    CAS  Google Scholar 

  • Evans D, Nijhout F, Parens R, Morales AJ, Bar-Yam YA (2016) A possible link between pyriproxyfen and microcephaly. Peer J Prepr 4:e1959v1. https://doi.org/10.7287/peerj.preprints.1959v1

  • Farag AT, Okazy AE, El-Aswad AF (2003) Developmental toxicity study of chlorpyrifos in rats. Reprod Toxicol 17:203–208

    CAS  Google Scholar 

  • Farag AT, Karkour T, El Okazy A (2006) Developmental toxicity of orally administered technical dimethoate in rats. Birth Defects Res Part B: Dev Reprod Toxicol 77:40–46

    CAS  Google Scholar 

  • Franc M, Genchi C, Bouhsira E, Warin S, Kaltsatos V, Baduel L, Genchi M (2012) Efficacy of dinotefuran, permithin and pyriproxyfen combination spot-on against Aedes aegypti mosquitoes on dogs. Vet Parasitol 189:333–337

    CAS  Google Scholar 

  • Freeman M (2016) Zika or insecticide pyriproxyfen behind microcephaly cases?. http://www.activistpost.com/2016/02/zika-orinsecticide-pyriproxyfen-behind-microcephaly-cases.html (19/08/2016)

  • Garcia AM, Fletcher T, Benevides FG, Orts E (1999) Parental agricultural work and selected congenital malformations. Am J Epidemiol 149:64–74

    CAS  Google Scholar 

  • Goldoni A, Klauck CR, da Silva ST, da Silva MD, Ardenghi PG, da Silva LB (2014) DNA damage in Wistar rats exposed to dithiocarbamate pesticide mancozeb. Folia Biol (Praha) 60:202–204

    CAS  Google Scholar 

  • Hamid S, Sharm S, Razdan S (2012) Carbaryl, a pesticide causes reproductive toxicity in albino rats. J Clin Exp Pathol 2:126

    Google Scholar 

  • Hanke W, Jurewicz J (2004) The risk of adverse reproductive and developmental disorders due to occupational pesticide exposure: an overview of current epidemiological evidence. Int J Occup Med Environ Health 17:223–243

    Google Scholar 

  • Harmon MA, Boehm MF, Heyman RA, Mangelsdorf DJ (1995) Activation of mammalian retinoid X receptors by the insect growth regulator methoprene. Proc Natl Acad Sci U S A 92:6157–6160

    CAS  Google Scholar 

  • Jeschke P, Nauen R, Schindler M, Elbert A (2010) Overview of the status and global strategy for neonicotinoids. J Agric Food Chem 59:2897–2908

    Google Scholar 

  • Kaushal V, Sharma S, Brar APS, Soni G (2007) NDEA induced oxidative stress in albino rats-impact of dietary protein level. Toxicol Int 14:33–39

    CAS  Google Scholar 

  • Khan RU, Durrani FR, Chand N, Anwar H (2010) Influence of feed supplementation with Cannabis sativa on quality of broilers carcass. Pak Vet J 30:34–38

    CAS  Google Scholar 

  • Koureas M, Tsakalof A, Tsatsakis A, Hadjichristodoulou C (2012) Systematic review of biomonitoring studies to determine the association between exposure to organophosphorus and pyrethroid insecticides and human health outcomes. Toxicol Lett 210:155–168

    CAS  Google Scholar 

  • Kristensen P, Irgens LM, Andersen A, Bye AS, Sundheim L (1997) Birth defects among offspring of Norwegian farmers, 1967–1991. Epidemiology 5:537–544

    Google Scholar 

  • Lacasana M, Vazquez-Grameix H, Borja-Aburto VH, Blanco-Munoz J, Romieu I, Aguilar-Garuno C, García AM (2006) Maternal and paternal occupational exposure to agricultural work and the risk of anencephaly. Occup Environ Med 63:649–656

    CAS  Google Scholar 

  • Mansour SA, Heikal TM, Mossa AH, Refaie AA (2008) Toxic effects of five insecticides and their mixture on male albino rats. J Egypt Soc Toxicol 39:85–94

    Google Scholar 

  • Marks AR, Harley K, Bradman A, Kogut K, Barr DB, Johnson C, Calderon N, Eskenazi B (2010) Organophosphate pesticide exposure and attention in young Mexican-American children: the CHAMACOS study. Environ Health Perspect 118:1768–1774

    CAS  Google Scholar 

  • Meeker JD, Ryan L, Barr DB, Hauser R (2006) Exposure to non-persistent insecticides and male reproductive hormones. Epidemiol 17:61–68

    Google Scholar 

  • Mehrnoush G, Mehrdad S, Saeid K (2013) Effect of pyriproxyfen on function and tissue of testis in adult rat. J Cur Res Rev 5:66–74

    CAS  Google Scholar 

  • Mondal S, Ghosh RC, Mate MS, Karmakar DB (2009) Effects of acetamiprid on immune system in female Wistar rats. Proc Zool Soc 62:109–117

    Google Scholar 

  • Mondal S, Ghosh RC, Mukhopadhyaya SK (2012) Studies on the electrolytes and microelements in Wistar rat following multiple exposures to acetamiprid. Toxicol Ind Health 28:422–427

    CAS  Google Scholar 

  • Mondal S, Ghosh RC, Karnam SS, Purohit K (2014) Toxicopathological changes on Wistar rat after multiple exposures to acetamiprid. Vet World 7:1058–1065

    Google Scholar 

  • Mossa AT, Refaie AA, Ramdan A (2011) Effect of exposure to mixture of four organophosphate insecticides at no observed adverse effect level dose on rat liver: the protective role of vitamin C. Environ Toxicol 5:323–335

    CAS  Google Scholar 

  • Palli SR, Riddiford LM, Hiruma K (1991) Juvenile hormone and “retinoic acid” receptors in Manduca epidermis. Insect Biochemistry 21:7–15

    CAS  Google Scholar 

  • Parens R, Nijhout HF, Morales A, Costa FX, Bar-Yam YA (2017) A possible link between pyriproxyfen and microcephaly. PLoS Curr 9

  • Rauh V, 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

    CAS  Google Scholar 

  • Red Universitaria de Ambiente Y Salud (REDUAS) (2016) REPORT from physicians in the crop-sprayed town regarding dengue-Zika, microcephaly, and massive spraying with chemical poisons. http://reduas.com.ar/report-from-physicians-in-the-crop-sprayed-townregarding-dengue-zika-microcephaly-and-massive-spraying-with-chemical-poisons/ (25/08/2016)

  • Ronda E, Regidor E, Garcia AM, Dominguez V (2005) Association between congenital anomalies and paternal exposure to agricultural pesticides depending on mother’s employment status. J Occup Environ Med 47:826

    Google Scholar 

  • Roy TS, Sharma V, Seidler FJ, Slotkin TA (2005) Quantitative morphological assessment reveals neuronal and glial deficits in hippocampus after a brief subtoxic exposure to chlorpyrifos in neonatal rats. Brain Res Dev Brain Res 155:71–80

    CAS  Google Scholar 

  • Rull RP, Ritz B, Shaw GM (2006) Neural tube defects and maternal residential proximity to agricultural pesticide applications. Am J Epidemiol 163:743–753

    Google Scholar 

  • Russo S (2016) The larvicide affair: the ripple effects of Zika misinformation in Brazil. http://blogs.plos.org/scied/2016/03/31/zika-vpesticides/ (19/08/2016)

  • Sekhar PR, Savithri Y, Kishor S, Jayasankar A, Rao KJ (2011) Synergistic effect of sodium fluoride and cypermethrin on the somatic index and histopathology of albino mice testes. Fluoride 44:103–111

    CAS  Google Scholar 

  • Shaw GM, Wasserman CR, O'Malley CD, Nelson V, Jackson RJ (1999) Maternal pesticide exposure from multiple sources and selected congenital anomalies. Epidemiology 10(1):60–66

    CAS  Google Scholar 

  • Slotkin TA, Bodwell BE, Levin ED, Seidler FJ (2008) Neonatal exposure to low doses of diazinon: long-term effects on neural cell development and acetylcholine systems. Environ Health Perspect 116(3):340–348

    CAS  Google Scholar 

  • Stillerman KP, Mattison DR, Giudice LC, Woodruff TJ (2008) Environmental exposures and adverse pregnancy outcomes: a review of the science. Reprod Sci 15:631–650

    Google Scholar 

  • Suvarna SK, Layton C, Bancroft JD (2012) Bancroft’s theory and practice of histological techniques. In: The hematoxylins and eosin, 7th edn. Churchill Livingstone Elsevier, UK, pp 146–186

    Google Scholar 

  • Swedish Toxicology Science Research Center (SWETOX) (2016) Pyriproxyfen and microcephaly: an investigation of potential ties to the ongoing “Zika epidemic”. http://swetox.se/wpcontent/ uploads/2016/03/ppf-zika.pdf (04/05/2016)

  • Taha TE, Gray RH (1993) Agricultural pesticide exposure and perinatal mortality in central Sudan. Bull. World Health Organ 71:317–321

    CAS  Google Scholar 

  • Tariq MI (2005) Leaching and degradation of cotton pesticides on different soil series of cotton growing areas of Punjab, Pakistan in lysimeters. Ph.D thesis, University of the Punjab, Lahore, Pakistan

  • Truong L, Gonnerman G, Simonich MT, Tanguay RL (2016) Assessment of the developmental and neurotoxicity of the mosquito control larvicide, pyriproxyfen, using embryonic zebrafish. Environ Pollut 218:1089–1093

    CAS  Google Scholar 

  • Uchendu C, Ambali SF, Ayo JO, EsievoK AN (2018) Body weight and hematological changes induced by chronic exposure to low levels of chlorpyrifos and deltamethrin combination in rats: the effect of alpha-lipoic acid. Comp Clin Path 27:1383–1388

    CAS  Google Scholar 

  • UNEP (1993) The Aral Sea: diagnostic study for the development of an action plan for the conservation of the Aral Sea. United Nations Environment Programme (UNEP), Nairobi

    Google Scholar 

  • Verma R, Mohanty B (2009) Early-life exposure to dimethoate-induced reproductive toxicity: evaluation of effects on pituitary-testicular axis of mice. Toxicol Sci 112(2):450–458

    CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to acknowledge Mr. Muhammad Waheed (Animal House Keeper) at Department of Zoology, Government College University, Lahore, Pakistan, for assistance during research work. No funding/research grants were availed for this research project.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Amna Shahid.

Ethics declarations

Ethical approval

The experimental protocols using animal model (mice) in the present study were approved by “Ethical Committee for the Treatment with Animals,” Government College University Lahore.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Responsible editor: Mohamed M. Abdel-Daim

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shahid, A., Saher, M. Repeated exposure of pyriproxyfen to pregnant female mice causes developmental abnormalities in prenatal pups. Environ Sci Pollut Res 27, 26998–27009 (2020). https://doi.org/10.1007/s11356-020-08656-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11356-020-08656-w

Keywords

Navigation