Skip to main content

Advertisement

Log in

Methylmercury-Induced Toxicopathologic Findings in Salivary Glands of Offspring Rats After Gestational and Lactational Exposure

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Methylmercury (MeHg) is one of the main global pollutants. The vulnerability of fetus and newborn to MeHg-induced changes is extensively reported, making relevant investigation possible for alternative sample matrix for human biological monitoring for at this stage of life. This study aimed to characterize tissue change effects of environmental–experimental MeHg on salivary glands of offspring rats after pre- and postnatal exposure. For this, pregnant Wistar rats were orally exposed to MeHg (40 μg/kg BW/day) or only vehicle (control group), from the gestational period to the end of the lactation period. Salivary glands (SG) were collected from the offspring to analyze possible Hg levels and main findings by histopathological evaluations and CK19 and α-SMA immunostaining. The results indicated that Hg levels in SG of intoxicated offspring were associated with histologic abnormalities, such as acinar atrophy and an increase in the intercellular matrix among the acini, as well as damages in the architecture of epithelium and myoepithelial cells, evidenced by a decrease in immunostaining area. Thus, this is the first study to show in the literature the toxicopathologic findings on SG of offspring after pre- and postnatal exposure to MeHg. Moreover, it presents the SG as an attractive target to futures studies, mainly in children exposed to environmentally relevant 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

Similar content being viewed by others

Data Availability

The quantitative and qualitative data used to support the findings of this study are included within the article.

References

  1. Clarkson TW, Magos L (2006) The toxicology of mercury and its chemical compounds. Crit Rev Toxicol 36(8):609–662. https://doi.org/10.1080/10408440600845619

    Article  CAS  PubMed  Google Scholar 

  2. Posin SL, Sharma S (2020) Mercury toxicity. In: StatPearls. StatPearls Publishing Copyright © 2020, StatPearls Publishing LLC, Treasure Island (FL)

  3. UN Environment (2019) Global mercury assessment 2018. ISBN: 978-92-807-3744-8

  4. Bjørklund G, Dadar M, Mutter J, Aaseth J (2017) The toxicology of mercury: current research and emerging trends. Environ Res 159:545–554. https://doi.org/10.1016/j.envres.2017.08.051

    Article  CAS  PubMed  Google Scholar 

  5. Gebeyehu HR, Bayissa LD (2020) Levels of heavy metals in soil and vegetables and associated health risks in Mojo area, Ethiopia. PLoS One 15(1):e0227883. https://doi.org/10.1371/journal.pone.0227883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Esdaile LJ, Chalker JM (2018) The mercury problem in artisanal and small-scale gold mining. 24(27):6905-6916. https://doi.org/10.1002/chem.201704840

  7. Berzas Nevado JJ, Rodríguez Martín-Doimeadios RC, Guzmán Bernardo FJ, Jiménez Moreno M, Herculano AM, do Nascimento JL, Crespo-López ME (2010) Mercury in the Tapajós River basin, Brazilian Amazon: a review. Environ Int 36(6):593–608. https://doi.org/10.1016/j.envint.2010.03.011

    Article  CAS  PubMed  Google Scholar 

  8. Bank MS (2020) The mercury science-policy interface: history, evolution and progress of the Minamata Convention. Sci Total Environ 722:137832. https://doi.org/10.1016/j.scitotenv.2020.137832

    Article  CAS  PubMed  Google Scholar 

  9. Hong C, Yu X, Liu J, Cheng Y, Rothenberg SE (2016) Low-level methylmercury exposure through rice ingestion in a cohort of pregnant mothers in rural China. Environ Res 150:519–527. https://doi.org/10.1016/j.envres.2016.06.038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Rodríguez Martín-Doimeadios RC, Berzas Nevado JJ, Guzmán Bernardo FJ, Jiménez Moreno M, Arrifano GPF, Herculano AM, do Nascimento JLM, Crespo-López ME (2014) Comparative study of mercury speciation in commercial fishes of the Brazilian Amazon. Environ Sci Pollut Res 21(12):7466–7479. https://doi.org/10.1007/s11356-014-2680-7

    Article  CAS  Google Scholar 

  11. Buck DG, Evers DC, Adams E, DiGangi J, Beeler B, Samánek J, Petrlik J, Turnquist MA, Speranskaya O, Regan K, Johnson S (2019) A global-scale assessment of fish mercury concentrations and the identification of biological hotspots. Sci Total Environ 687:956–966. https://doi.org/10.1016/j.scitotenv.2019.06.159

    Article  CAS  PubMed  Google Scholar 

  12. Rice KM, Walker EM Jr, Wu M, Gillette C, Blough ER (2014) Environmental mercury and its toxic effects. J Prev Med Public Health 47(2):74–83. https://doi.org/10.3961/jpmph.2014.47.2.74

    Article  PubMed  PubMed Central  Google Scholar 

  13. Ceccatelli S, Bose R, Edoff K, Onishchenko N, Spulber S (2013) Long-lasting neurotoxic effects of exposure to methylmercury during development. J Intern Med 273(5):490–497. https://doi.org/10.1111/joim.12045

    Article  CAS  PubMed  Google Scholar 

  14. Ursinyova M, Masanova V, Uhnakova I, Murinova LP, Patayova H, Rausova K, Trnovec T, Stencl J, Gajdos M (2019) Prenatal and early postnatal exposure to total mercury and methylmercury from low maternal fish consumption. Biol Trace Elem Res 191(1):16–26. https://doi.org/10.1007/s12011-018-1585-6

    Article  CAS  PubMed  Google Scholar 

  15. Rocha JB, Aschner M, Dórea JG, Ceccatelli S, Farina M, Silveira LC (2012) Mercury toxicity. J Biomed Biotechnol 2012:831890–831892. https://doi.org/10.1155/2012/831890

    Article  PubMed  PubMed Central  Google Scholar 

  16. Björnberg KA, Vahter M, Berglund B, Niklasson B, Blennow M, Sandborgh-Englund G (2005) Transport of methylmercury and inorganic mercury to the fetus and breast-fed infant. Environ Health Perspect 113(10):1381–1385. https://doi.org/10.1289/ehp.7856

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bittencourt LO, Puty B, Charone S, Aragão WAB, Farias-Junior PM, Silva MCF, Crespo-Lopez ME, Leite AL, Buzalaf MAR, Lima RR (2017) Oxidative biochemistry disbalance and changes on proteomic profile in salivary glands of rats induced by chronic exposure to methylmercury. Oxidative Med Cell Longev 2017:5653291–5653215. https://doi.org/10.1155/2017/5653291

    Article  CAS  Google Scholar 

  18. Farias-Junior PMA, Teixeira FB, Fagundes NCF, Miranda GHN, Oliveira Bittencourt L, de Oliveira Paraense RS, Silva MCF, Sagica F, de Oliveira EH, Crespo-López ME, Lima RR (2017) Chronic intoxication by methylmercury leads to oxidative damage and cell death in salivary glands of rats. Metallomics 9(12):1778–1785. https://doi.org/10.1039/c7mt00168a

    Article  CAS  PubMed  Google Scholar 

  19. Lima LAO, Bittencourt LO, Puty B, Fernandes RM, Nascimento PC, Silva MCF, Alves-Junior SM, Pinheiro JJV, Lima RR (2018) Methylmercury intoxication promotes metallothionein response and cell damage in salivary glands of rats. Biol Trace Elem Res 185(1):135–142. https://doi.org/10.1007/s12011-017-1230-9

    Article  CAS  PubMed  Google Scholar 

  20. Maruyama CL, Monroe MM, Hunt JP, Buchmann L, Baker OJ (2019) Comparing human and mouse salivary glands: a practice guide for salivary researchers. Oral Dis 25(2):403–415. https://doi.org/10.1111/odi.12840

    Article  CAS  PubMed  Google Scholar 

  21. Kingsnorth AN, Skandalakis PN, Colborn GL, Weidman TA, Skandalakis LJ, Skandalakis JE (2000) Embryology, anatomy, and surgical applications of the preperitoneal space. Surg Clin North Am 80(1):1–24. https://doi.org/10.1016/s0039-6109(05)70394-7

    Article  CAS  PubMed  Google Scholar 

  22. Michalke B, Rossbach B, Göen T, Schäferhenrich A, Scherer G (2015) Saliva as a matrix for human biomonitoring in occupational and environmental medicine. Int Arch Occup Environ Health 88(1):1–44. https://doi.org/10.1007/s00420-014-0938-5

    Article  CAS  PubMed  Google Scholar 

  23. Caporossi L, Santoro A, Papaleo B (2010) Saliva as an analytical matrix: state of the art and application for biomonitoring. Biomarkers 15(6):475–487. https://doi.org/10.3109/1354750x.2010.481364

    Article  CAS  PubMed  Google Scholar 

  24. Council NR (2011) Guide for the care and use of laboratory animals, Eighth edn. The National Academies Press, Washington, DC. https://doi.org/10.17226/12910

    Book  Google Scholar 

  25. Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG (2010) Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol 8(6):e1000412. https://doi.org/10.1371/journal.pbio.1000412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kong HK, Wong MH, Chan HM, Lo SC (2013) Chronic exposure of adult rats to low doses of methylmercury induced a state of metabolic deficit in the somatosensory cortex. J Proteome Res 12(11):5233–5245. https://doi.org/10.1021/pr400356v

    Article  CAS  PubMed  Google Scholar 

  27. Liang J, Inskip M, Newhook D, Messier C (2009) Neurobehavioral effect of chronic and bolus doses of methylmercury following prenatal exposure in C57BL/6 weanling mice. Neurotoxicol Teratol 31(6):372–381. https://doi.org/10.1016/j.ntt.2009.08.007

    Article  CAS  PubMed  Google Scholar 

  28. Kirkpatrick M, Benoit J, Everett W, Gibson J, Rist M, Fredette N (2015) The effects of methylmercury exposure on behavior and biomarkers of oxidative stress in adult mice. Neurotoxicology 50:170–178. https://doi.org/10.1016/j.neuro.2015.07.001

    Article  CAS  PubMed  Google Scholar 

  29. Taga R, Sesso A (1979) Ultrastructural studies on developing parotid gland of the rat at early postnatal periods. Arch Histol Jpn 42(4):427–444. https://doi.org/10.1679/aohc1950.42.427

    Article  CAS  PubMed  Google Scholar 

  30. Santana L, Bittencourt LO, Nascimento PC, Fernandes RM, Teixeira FB, Fernandes LMP, Freitas Silva MC, Nogueira LS, Amado LL, Crespo-Lopez ME, Maia C, Lima RR (2019) Low doses of methylmercury exposure during adulthood in rats display oxidative stress, neurodegeneration in the motor cortex and lead to impairment of motor skills. J Trace Elem Med Biol 51:19–27. https://doi.org/10.1016/j.jtemb.2018.09.004

    Article  CAS  PubMed  Google Scholar 

  31. Bohl L, Merlo C, Carda C, Gomez de Ferraris ME, Carranza M (2008) Morphometric analysis of the parotid gland affected by alcoholic sialosis. J Oral Pathol Med 37(8):499–503. https://doi.org/10.1111/j.1600-0714.2008.00648.x

    Article  PubMed  Google Scholar 

  32. Chu PG, Weiss LM (2002) Keratin expression in human tissues and neoplasms. Histopathology 40(5):403–439. https://doi.org/10.1046/j.1365-2559.2002.01387.x

    Article  CAS  PubMed  Google Scholar 

  33. Ogawa Y (2003) Immunocytochemistry of myoepithelial cells in the salivary glands. Prog Histochem Cytochem 38(4):343–426. https://doi.org/10.1016/S0079-6336(03)80001-3

    Article  CAS  PubMed  Google Scholar 

  34. Ronchetti R, Zuurbier M, Jesenak M, Koppe JG, Ahmed UF, Ceccatelli S, Villa MP (2006) Children’s health and mercury exposure. 95(s453):36-44. https://doi.org/10.1080/08035250600886157

  35. Branch WUDC (2008) Guidance for identifying populations at risk from mercury exposure.

  36. de Paula Fonseca Arrifano G, Del Carmen Rodriguez Martin-Doimeadios R, Jiménez-Moreno M, Augusto-Oliveira M, Rogério Souza-Monteiro J, Paraense R, Rodrigues Machado C, Farina M, Macchi B, do Nascimento JLM, Crespo-Lopez ME (2018) Assessing mercury intoxication in isolated/remote populations: increased S100B mRNA in blood in exposed riverine inhabitants of the Amazon. Neurotoxicology 68:151–158. https://doi.org/10.1016/j.neuro.2018.07.018

    Article  CAS  PubMed  Google Scholar 

  37. Santos Serrão de Castro N, de Oliveira Lima M (2018) Hair as a biomarker of long term mercury exposure in Brazilian Amazon: a systematic review. Int J Environ Res Public Health 15(3). https://doi.org/10.3390/ijerph15030500

  38. Arrifano GPF, Martín-Doimeadios RCR, Jiménez-Moreno M, Fernández-Trujillo S, Augusto-Oliveira M, Souza-Monteiro JR, Macchi BM, Alvarez-Leite JI, do Nascimento JLM, Amador MT, Santos S, Ribeiro-Dos-Santos Â, Silva-Pereira LC, Oriá RB, Crespo-Lopez ME (2018) Genetic susceptibility to neurodegeneration in Amazon: apolipoprotein E genotyping in vulnerable populations exposed to mercury. Front Genet 9:285. https://doi.org/10.3389/fgene.2018.00285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Arrifano GPF, Martín-Doimeadios RCR, Jiménez-Moreno M, Ramírez-Mateos V, da Silva NFS, Souza-Monteiro JR, Augusto-Oliveira M, Paraense RSO, Macchi BM, do Nascimento JLM, Crespo-Lopez ME (2018) Large-scale projects in the Amazon and human exposure to mercury: the case-study of the Tucuruí Dam. Ecotoxicol Environ Saf 147:299–305. https://doi.org/10.1016/j.ecoenv.2017.08.048

    Article  CAS  PubMed  Google Scholar 

  40. Council NR (2000) Toxicological effects of methylmercury. The National Academies Press, Washington, DC. https://doi.org/10.17226/9899

    Book  Google Scholar 

  41. Al-Saleh I, Abduljabbar M, Al-Rouqi R, Elkhatib R, Alshabbaheen A, Shinwari N (2013) Mercury (Hg) exposure in breast-fed infants and their mothers and the evidence of oxidative stress. Biol Trace Elem Res 153(1-3):145–154. https://doi.org/10.1007/s12011-013-9687-7

    Article  CAS  PubMed  Google Scholar 

  42. Day JJ, Reed MN, Newland MC (2005) Neuromotor deficits and mercury concentrations in rats exposed to methyl mercury and fish oil. Neurotoxicol Teratol 27(4):629–641. https://doi.org/10.1016/j.ntt.2005.03.011

    Article  CAS  PubMed  Google Scholar 

  43. Gervais EM, Sequeira SJ, Wang W, Abraham S, Kim JH, Leonard D, DeSantis KA, Larsen M (2016) Par-1b is required for morphogenesis and differentiation of myoepithelial cells during salivary gland development. Organogenesis 12(4):194–216. https://doi.org/10.1080/15476278.2016.1252887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Porcheri C, Mitsiadis TA (2019) Physiology, pathology and regeneration of salivary glands. Cells 8(9):976. https://doi.org/10.3390/cells8090976

    Article  CAS  PubMed Central  Google Scholar 

  45. Wells KL, Gaete M, Matalova E, Deutsch D, Rice D, Tucker AS (2013) Dynamic relationship of the epithelium and mesenchyme during salivary gland initiation: the role of Fgf10. Biol Open 2(10):981–989. https://doi.org/10.1242/bio.20135306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Sisto M, Lisi S, Ribatti D (2018) The role of the epithelial-to-mesenchymal transition (EMT) in diseases of the salivary glands. Histochem Cell Biol 150(2):133–147. https://doi.org/10.1007/s00418-018-1680-y

    Article  CAS  PubMed  Google Scholar 

  47. Millsop JW, Wang EA, Fazel N (2017) Etiology, evaluation, and management of xerostomia. Clin Dermatol 35(5):468–476. https://doi.org/10.1016/j.clindermatol.2017.06.010

    Article  PubMed  Google Scholar 

  48. Epstein JB, Villines DC, Sroussi HY (2015) Oral symptoms and oral function in people with Sjögren’s syndrome. Clin Exp Rheumatol 33(1):132–133

    PubMed  Google Scholar 

  49. Mauri-Obradors E, Estrugo-Devesa A, Jané-Salas E, Viñas M, López-López J (2017) Oral manifestations of diabetes mellitus. A systematic review. Med Oral Patol Oral Cir Bucal 22(5):e586–e594. https://doi.org/10.4317/medoral.21655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Talha B, Swarnkar SA (2020) Xerostomia. In: StatPearls. StatPearls Publishing Copyright © 2020, StatPearls Publishing LLC, Treasure Island (FL)

Download references

Acknowledgments

The authors would like to thank the Federal University of Pará and Federal University of Rio Grande do Sul for technical and scientific support.

Funding

This work was supported by the Research Pro-Rectory of Federal University of Pará (PROPESP, UFPA, Brazil), Brazilian National Council for Scientific and Technological Development (CNPq), and Programa Nacional de Cooperação Acadêmica na Amazônia—PROCAD/Amazônia by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). This study was financed in part by the CAPES —Finance Code 001.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rafael Rodrigues Lima.

Ethics declarations

All procedures were reviewed and approved by the ethics committee on animal experimentation of the UFPA (protocol number 8613011217/CEUA-UFPA), according to the Guidelines for the Care and Use of Laboratory Animals [24]. Besides, this study followed the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines (Table S1) [25].

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

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

Electronic supplementary material

ESM 1

(DOCX 858 kb).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nascimento, P.C., Ferreira, M.M., Balbinot, K.M. et al. Methylmercury-Induced Toxicopathologic Findings in Salivary Glands of Offspring Rats After Gestational and Lactational Exposure. Biol Trace Elem Res 199, 2983–2991 (2021). https://doi.org/10.1007/s12011-020-02409-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-020-02409-z

Keywords

Navigation