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Environmental Science and Pollution Research

, Volume 26, Issue 31, pp 32322–32332 | Cite as

Mercury chloride exposure induces DNA damage, reduces fertility, and alters somatic and germline cells in Drosophila melanogaster ovaries

  • Luis Humberto Mojica-VázquezEmail author
  • Diana Madrigal-Zarraga
  • Rocío García-Martínez
  • Muriel Boube
  • María Elena Calderón-Segura
  • Justine OyallonEmail author
Research Article

Abstract

Mercury exposure has been shown to affect the reproductive system in many organisms, although the molecular mechanisms are still elusive. In the present study, we exposed Drosophila melanogaster Canton-S adult females to concentrations of 0 mM, 0.1 mM, 0.3 mM, 3 mM, and 30 mM of mercury chloride (HgCl2) for 24 h, 48 h, or 72 h to determine how mercury could affect fertility. Alkaline assays performed on dissected ovaries showed that mercury induced DNA damage that is not only dose-dependent but also time-dependent. All ovaries treated for 72 h have incorporated mercury and exhibit size reduction. Females treated with 30 mM HgCl2, the highest dose, had atrophied ovaries and exhibited a drastic 7-fold reduction in egg laying. Confocal microscopy analysis revealed that exposure to HgCl2 disrupts germinal and somatic cell organization in the germarium and leads to the aberrant expression of a germline-specific gene in somatic follicle cells in developing egg chambers. Together, these results highlight the potential long-term impact of mercury on germline and ovarian cells that might involve gene deregulation.

Keywords

Drosophila melanogaster DNA damage Gene regulation Fertility Germline Ovarian somatic cells Mercury chloride 

Notes

Acknowledgments

We thank M. López-Carrasco, S. Gómez-Arroyo, J. Cortés-Eslava, A. R. Flores-Márquez, and the Centro de Ciencias de la Atmosfera, UNAM, for the infrastructural facilities. We are grateful to Jessica E. Treisman, Alain Vincent, Marc Amoyel, and Yannis E. Mavromatakis for their scientific feedback and to Dianne Heath for her careful proofreading of the manuscript. Imaging was acquired thanks to the UNICUA-LANSBIODyT project from CONACYT 280317 Facultad de Ciencias, UNAM.

Funding information

This work was supported by resources provided by the CCA, UNAM, and CBD, Universite Paul Sabatier, Toulouse III. LHMV was supported by Mexican CONACYT.

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests.

References

  1. Abnoos H, Fereidoni M, Mahdavi-Shahri N, Haddad F, Jalal R (2013) Developmental study of mercury effects on the fruit fly (Drosophila melanogaster). Interdiscip Toxicol 6:34–40.  https://doi.org/10.2478/intox-2013-0007 CrossRefGoogle Scholar
  2. Altunkaynak BZ, Akgül N, Yahyazadeh A, Altunkaynak ME, Turkmen AP, Akgül HM, Ünal B (2016) Effect of mercury vapor inhalation on rat ovary: stereology and histopathology. J Obstet Gynaecol Res 42:410–416.  https://doi.org/10.1111/jog.12911 CrossRefGoogle Scholar
  3. Asmuss M, Mullenders LH, Eker A, Hartwig A (2000) Differential effects of toxic metal compounds on the activities of Fpg and XPA, two zinc finger proteins involved in DNA repair. Carcinogenesis 21:2097–2104.  https://doi.org/10.1093/carcin/21.11.2097 CrossRefGoogle Scholar
  4. Bass TM, Grandison RC, Wong R, Martinez P, Partridge L, Piper MD (2007) Optimization of dietary restriction protocols in Drosophila. J Gerontol A Biol Sci Med Sci 62:1071–1081.  https://doi.org/10.1093/gerona/62.10.1071 CrossRefGoogle Scholar
  5. Betti C, Davini T, Barale R (1992) Genotoxic activity of methyl mercury chloride and dimethyl mercury in human lymphocytes. Mutat Res 281:255–260CrossRefGoogle Scholar
  6. Breton J, Massart S, Vandamme P, De Brandt E, Pot B, Foligné B (2013) Ecotoxicology inside the gut: impact of heavy metals on the mouse microbiome. BMC Pharmacol Toxicol 14:62.  https://doi.org/10.1186/2050-6511-14-62 CrossRefGoogle Scholar
  7. Calap-Quintana P, González-Fernández J, Sebastiá-Ortega N, Llorens JV, Moltó MD (2017) Drosophila melanogaster models of metal-related human diseases and metal toxicity. Int J Mol Sci 18.  https://doi.org/10.3390/ijms18071456 CrossRefGoogle Scholar
  8. Castaño A, Pedraza-Díaz S, Cañas AI, Pérez-Gómez B, Ramos JJ, Bartolomé M, Pärt P, Soto EP, Motas M, Navarro C, Calvo E, Esteban M (2019) Mercury levels in blood, urine and hair in a nation-wide sample of Spanish adults. Sci Total Environ 670:262–270.  https://doi.org/10.1016/j.scitotenv.2019.03.174 CrossRefGoogle Scholar
  9. Cebulska-Wasilewska A, Panek A, Zabinski Z, Moszczynski P (2005a) Influence of mercury vapors on lymphocytes in vivo and on their susceptibility to UV-C and X-rays, and repair efficiency in vitro. Med Pr 56:303–310Google Scholar
  10. Cebulska-Wasilewska A, Panek A, Zabinski Z, Moszczynski P, Au WW (2005b) Occupational exposure to mercury vapour on genotoxicity and DNA repair. Mutat Res 586:102–114.  https://doi.org/10.1016/j.mrgentox.2005.06.009 CrossRefGoogle Scholar
  11. Chen Z, Wu X, Luo H, Zhao L, Ji X, Qiao X, Jin Y, Liu W (2016) Acute exposure of mercury chloride stimulates the tissue regeneration program and reactive oxygen species production in the Drosophila midgut. Environ Toxicol Pharmacol 41:32–38.  https://doi.org/10.1016/j.etap.2015.11.009 CrossRefGoogle Scholar
  12. Counter SA, Buchanan LH (2004) Mercury exposure in children: a review. Toxicol Appl Pharmacol 198:209–230.  https://doi.org/10.1016/j.taap.2003.11.032 CrossRefGoogle Scholar
  13. Coux RX, Teixeira FK, Lehmann R (2018) L(3)mbt and the LINT complex safeguard cellular identity in the Drosophila ovary. Development 145:dev160721.  https://doi.org/10.1242/dev.160721 CrossRefGoogle Scholar
  14. Crespo-López ME, Macêdo GL, Pereira SI, Arrifano GP, Picanço-Diniz DL, do Nascimento JL, Herculano AM (2009) Mercury and human genotoxicity: critical considerations and possible molecular mechanisms. Pharmacol Res 60:212–220.  https://doi.org/10.1016/j.phrs.2009.02.011 CrossRefGoogle Scholar
  15. Dansereau DA, Lasko P (2008) The development of germline stem cells in Drosophila. Methods Mol Biol 450:3–26.  https://doi.org/10.1007/978-1-60327-214-8_1 CrossRefGoogle Scholar
  16. Davis BJ, Price HC, O’Connor RW, Fernando R, Rowland AS, Morgan DL (2001) Mercury vapor and female reproductive toxicity. Toxicol Sci 59:291–296CrossRefGoogle Scholar
  17. de Castro E Sousa JM et al (2017) Cytotoxicity and genotoxicity of Guaribas river water (Piauí, Brazil), influenced by anthropogenic action. Environ Monit Assess 189:301.  https://doi.org/10.1007/s10661-017-6015-2 CrossRefGoogle Scholar
  18. De Flora S, Bennicelli C, Bagnasco M (1994) Genotoxicity of mercury compounds. A review. Mutat Res 317:57–79CrossRefGoogle Scholar
  19. Deng WM, Bownes M (1998) Patterning and morphogenesis of the follicle cell epithelium during Drosophila oogenesis. Int J Dev Biol 42:541–552Google Scholar
  20. Dus M, Min S, Keene AC, Lee GY, Suh GS (2011) Taste-independent detection of the caloric content of sugar in Drosophila. Proc Natl Acad Sci U S A 108:11644–11649.  https://doi.org/10.1073/pnas.1017096108 CrossRefGoogle Scholar
  21. Ehrenstein C, Shu P, Wickenheiser EB, Hirner AV, Dolfen M, Emons H, Obe G (2002) Methyl mercury uptake and associations with the induction of chromosomal aberrations in Chinese hamster ovary (CHO) cells. Chem Biol Interact 141:259–274CrossRefGoogle Scholar
  22. Farina M, Rocha JB, Aschner M (2011) Mechanisms of methylmercury-induced neurotoxicity: evidence from experimental studies. Life Sci 89:555–563.  https://doi.org/10.1016/j.lfs.2011.05.019 CrossRefGoogle Scholar
  23. Gancz D, Lengil T, Gilboa L (2011) Coordinated regulation of niche and stem cell precursors by hormonal signaling. PLoS Biol 9:e1001202.  https://doi.org/10.1371/journal.pbio.1001202 CrossRefGoogle Scholar
  24. Gateff E, Löffler T, Wismar J (1993) A temperature-sensitive brain tumor suppressor mutation of Drosophila melanogaster: developmental studies and molecular localization of the gene. Mech Dev 41:15–31CrossRefGoogle Scholar
  25. Geier DA, Carmody T, Kern JK, King PG, Geier MR (2013) A significant dose-dependent relationship between mercury exposure from dental amalgams and kidney integrity biomarkers: a further assessment of the Casa Pia children’s dental amalgam trial. Hum Exp Toxicol 32:434–440.  https://doi.org/10.1177/0960327112455671 CrossRefGoogle Scholar
  26. Hales KG, Korey CA, Larracuente AM, Roberts DM (2015) Genetics on the fly: a primer on the Drosophila model system. Genetics 201:815–842.  https://doi.org/10.1534/genetics.115.183392 CrossRefGoogle Scholar
  27. Hong YS, Kim YM, Lee KE (2012) Methylmercury exposure and health effects. J Prev Med Public Health 45:353–363.  https://doi.org/10.3961/jpmph.2012.45.6.353 CrossRefGoogle Scholar
  28. Iavicoli I, Fontana L, Bergamaschi A (2009) The effects of metals as endocrine disruptors. J Toxicol Environ Health B Crit Rev 12:206–223.  https://doi.org/10.1080/10937400902902062 CrossRefGoogle Scholar
  29. Jaishankar M, Tseten T, Anbalagan N, Mathew BB, Beeregowda KN (2014) Toxicity, mechanism and health effects of some heavy metals. Interdiscip Toxicol 7:60–72.  https://doi.org/10.2478/intox-2014-0009 CrossRefGoogle Scholar
  30. Janic A, Mendizabal L, Llamazares S, Rossell D, Gonzalez C (2010) Ectopic expression of germline genes drives malignant brain tumor growth in Drosophila. Science 330:1824–1827.  https://doi.org/10.1126/science.1195481 CrossRefGoogle Scholar
  31. Jonsson S, Skyllberg U, Nilsson MB, Lundberg E, Andersson A, Björn E (2014) Differentiated availability of geochemical mercury pools controls methylmercury levels in estuarine sediment and biota. Nat Commun 5:4624.  https://doi.org/10.1038/ncomms5624 CrossRefGoogle Scholar
  32. Khan AT, Atkinson A, Graham TC, Thompson SJ, Ali S, Shireen KF (2004) Effects of inorganic mercury on reproductive performance of mice. Food Chem Toxicol 42:571–577.  https://doi.org/10.1016/j.fct.2003.10.018 CrossRefGoogle Scholar
  33. Khan F, Momtaz S, Abdollahi M (2019) The relationship between mercury exposure and epigenetic alterations regarding human health, risk assessment and diagnostic strategies. J Trace Elem Med Biol 52:37–47.  https://doi.org/10.1016/j.jtemb.2018.11.006 CrossRefGoogle Scholar
  34. Kirubagaran R, Joy KP (1991) Changes in adrenocortical-pituitary activity in the catfish, Clarias batrachus (L.), after mercury treatment. Ecotoxicol Environ Saf 22:36–44CrossRefGoogle Scholar
  35. Lamperti AA, Printz RH (1973) Effects of mercuric chloride on the reproductive cycle of the female hamster. Biol Reprod 8:378–387CrossRefGoogle Scholar
  36. Lewis SA, Becker PH, Furness RW (1993) Mercury levels in eggs, tissues, and feathers of herring gulls Larus argentatus from the German Wadden Sea Coast. Environ Pollut 80:293–299CrossRefGoogle Scholar
  37. Li Y, Jiang Y, Yan XP (2006) Probing mercury species-DNA interactions by capillary electrophoresis with on-line electrothermal atomic absorption spectrometric detection. Anal Chem 78:6115–6120.  https://doi.org/10.1021/ac060644a CrossRefGoogle Scholar
  38. Losick VP, Morris LX, Fox DT, Spradling A (2011) Drosophila stem cell niches: a decade of discovery suggests a unified view of stem cell regulation. Dev Cell 21:159–171.  https://doi.org/10.1016/j.devcel.2011.06.018 CrossRefGoogle Scholar
  39. Masud S, Singh IJ, Ram RN (2009) Histophysiological responses in ovary and liver of Cyprinus carpio after short term exposure to safe concentration of mercuric chloride and recovery pattern. J Environ Biol 30:399–403Google Scholar
  40. Mendes CC, Mirth CK (2016) Stage-specific plasticity in ovary size is regulated by insulin/insulin-like growth factor and ecdysone signaling in Drosophila. Genetics 202:703–719.  https://doi.org/10.1534/genetics.115.179960 CrossRefGoogle Scholar
  41. Mocevic E, Specht IO, Marott JL, Giwercman A, Jönsson BAG, Toft G, Lundh T, Peter Bonde J (2013) Environmental mercury exposure, semen quality and reproductive hormones in Greenlandic Inuit and European men: a cross-sectional study. Asian J Androl 15:97–104.  https://doi.org/10.1038/aja.2012.121 CrossRefGoogle Scholar
  42. Mojica-Vázquez LH, Benetah MH, Baanannou A, Bernat-Fabre S, Deplancke B, Cribbs DL, Bourbon HM, Boube M (2017) Tissue-specific enhancer repression through molecular integration of cell signaling inputs. PLoS Genet 13:e1006718.  https://doi.org/10.1371/journal.pgen.1006718 CrossRefGoogle Scholar
  43. Nystul T, Spradling A (2010) Regulation of epithelial stem cell replacement and follicle formation in the Drosophila ovary. Genetics 184:503–515.  https://doi.org/10.1534/genetics.109.109538 CrossRefGoogle Scholar
  44. Panagopoulos DJ (2012) Effect of microwave exposure on the ovarian development of Drosophila melanogaster. Cell Biochem Biophys 63:121–132.  https://doi.org/10.1007/s12013-012-9347-0 CrossRefGoogle Scholar
  45. Paula MT, Zemolin AP, Vargas AP, Golombieski RM, Loreto ELS, Saidelles AP, Picoloto RS, Flores EMM, Pereira AB, Rocha JBT, Merritt TJS, Franco JL, Posser T (2014) Effects of Hg(II) exposure on MAPK phosphorylation and antioxidant system in D. melanogaster. Environ Toxicol 29:621–630.  https://doi.org/10.1002/tox.21788 CrossRefGoogle Scholar
  46. Pereira CS, Guilherme SI, Barroso CM, Verschaeve L, Pacheco MG, Mendo SA (2010) Evaluation of DNA damage induced by environmental exposure to mercury in Liza aurata using the comet assay. Arch Environ Contam Toxicol 58:112–122.  https://doi.org/10.1007/s00244-009-9330-y CrossRefGoogle Scholar
  47. Pirzadah TB, Malik B, Tahir I, Irfan QM, Rehman RU (2018) Characterization of mercury-induced stress biomarkers in Fagopyrum tataricum plants. Int J Phytoremediation 20:225–236.  https://doi.org/10.1080/15226514.2017.1374332 CrossRefGoogle Scholar
  48. Pletz J, Sánchez-Bayo F, Tennekes HA (2016) Dose-response analysis indicating time-dependent neurotoxicity caused by organic and inorganic mercury—implications for toxic effects in the developing brain. Toxicology 347–349:1–5.  https://doi.org/10.1016/j.tox.2016.02.006 CrossRefGoogle Scholar
  49. Queiroz EK, Waissmann W (2006) Occupational exposure and effects on the male reproductive system. Cad Saude Publica 22:485–493.  https://doi.org/10.1590/s0102-311x2006000300003 CrossRefGoogle Scholar
  50. Reddy PS, Tuberty SR, Fingerman M (1997) Effects of cadmium and mercury on ovarian maturation in the red swamp crayfish, Procambarus clarkii. Ecotoxicol Environ Saf 37:62–65.  https://doi.org/10.1006/eesa.1997.1523 CrossRefGoogle Scholar
  51. Reiff T, Jacobson J, Cognigni P, Antonello Z, Ballesta E, Tan KJ, Yew JY, Dominguez M, Miguel-Aliaga I (2015) Endocrine remodelling of the adult intestine sustains reproduction in Drosophila. Elife 4:e06930.  https://doi.org/10.7554/eLife.06930 CrossRefGoogle Scholar
  52. Rice KM, Walker EM, Wu M, Gillette C, Blough ER (2014) Environmental mercury and its toxic effects. J Prev Med Public Health 47:74–83.  https://doi.org/10.3961/jpmph.2014.47.2.74 CrossRefGoogle Scholar
  53. Rozgaj R, Kasuba V, Blanusa M (2005) Mercury chloride genotoxicity in rats following oral exposure, evaluated by comet assay and micronucleus test. Arh Hig Rada Toksikol 56:9–15Google Scholar
  54. Rzymski P, Tomczyk K, Poniedziałek B, Opala T, Wilczak M (2015) Impact of heavy metals on the female reproductive system. Ann Agric Environ Med 22:259–264.  https://doi.org/10.5604/12321966.1152077 CrossRefGoogle Scholar
  55. Sarker S, Vashistha D, Saha Sarker M, Sarkar A (2018) DNA damage in marine rock oyster (Saccostrea cucullata) exposed to environmentally available PAHs and heavy metals along the Arabian Sea coast. Ecotoxicol Environ Saf 151:132–143.  https://doi.org/10.1016/j.ecoenv.2018.01.004 CrossRefGoogle Scholar
  56. Schuurs AH (1999) Reproductive toxicity of occupational mercury. A review of the literature. J Dent 27:249–256CrossRefGoogle Scholar
  57. Sengupta P, Banerjee R, Nath S, Das S, Banerjee S (2015) Metals and female reproductive toxicity. Hum Exp Toxicol 34:679–697.  https://doi.org/10.1177/0960327114559611 CrossRefGoogle Scholar
  58. Shim J, Gururaja-Rao S, Banerjee U (2013) Nutritional regulation of stem and progenitor cells in Drosophila. Development 140:4647–4656.  https://doi.org/10.1242/dev.079087 CrossRefGoogle Scholar
  59. Shukla AK, Pragya P, Chowdhuri DK (2011) A modified alkaline Comet assay for in vivo detection of oxidative DNA damage in Drosophila melanogaster. Mutat Res 726:222–226.  https://doi.org/10.1016/j.mrgentox.2011.09.017 CrossRefGoogle Scholar
  60. Sikorski R, Juszkiewicz T, Paszkowski T, Szprengier-Juszkiewicz T (1987) Women in dental surgeries: reproductive hazards in occupational exposure to metallic mercury. Int Arch Occup Environ Health 59:551–557CrossRefGoogle Scholar
  61. Siraj M, Khisroon M, Khan A, Zaidi F, Ullah A, Rahman G (2018) Bio-monitoring of tissue accumulation and genotoxic effect of heavy metals in Cyprinus carpio from River Kabul Khyber Pakhtunkhwa Pakistan. Bull Environ Contam Toxicol 100:344–349.  https://doi.org/10.1007/s00128-017-2265-5 CrossRefGoogle Scholar
  62. Snyder RD (1988) Role of active oxygen species in metal-induced DNA strand breakage in human diploid fibroblasts. Mutat Res 193:237–246Google Scholar
  63. Stadnicka A (1980) Localization of mercury in the rat ovary after oral administration of mercuric chloride. Acta Histochem 67:227–233.  https://doi.org/10.1016/s0065-1281(80)80026-2 CrossRefGoogle Scholar
  64. Sunjog K, Kolarević S, Héberger K, Gačić Z, Knežević-Vukčević J, Vuković-Gačić B, Lenhardt M (2013) Comparison of comet assay parameters for estimation of genotoxicity by sum of ranking differences. Anal Bioanal Chem 405:4879–4885.  https://doi.org/10.1007/s00216-013-6909-y CrossRefGoogle Scholar
  65. Suzuki N, Yamamoto M, Watanabe K, Kambegawa A, Hattori A (2004) Both mercury and cadmium directly influence calcium homeostasis resulting from the suppression of scale bone cells: the scale is a good model for the evaluation of heavy metals in bone metabolism. J Bone Miner Metab 22:439–446.  https://doi.org/10.1007/s00774-004-0505-3 CrossRefGoogle Scholar
  66. Turkez H, Geyikoglu F, Tatar A, Keles MS, Kaplan I (2012) The effects of some boron compounds against heavy metal toxicity in human blood. Exp Toxicol Pathol 64:93–101.  https://doi.org/10.1016/j.etp.2010.06.011 CrossRefGoogle Scholar
  67. USEPA (2002). Method 1631 Revision E: Mercury in Water by Oxidation, Purge and Trap, and Cold Vapor Atomic Fluorescence Spectrometry. EPA-821-R-02–019. Office of Water.), U.S. Environmental Protection Agency, Washington, DC.Google Scholar
  68. Wainman BC, Kesner JS, Martin ID, Meadows JW, Krieg EF, Nieboer E, Tsuji LJ (2016) Menstrual cycle perturbation by organohalogens and elements in the Cree of James Bay, Canada. Chemosphere 149:190–201.  https://doi.org/10.1016/j.chemosphere.2015.12.056 CrossRefGoogle Scholar
  69. Weber DN (2006) Dose-dependent effects of developmental mercury exposure on C-start escape responses of larval zebrafish Danio rerio. J Fish Biol 69:65–94CrossRefGoogle Scholar
  70. Wong LC, Schedl P (2006) Dissection of Drosophila ovaries. J Vis Exp:52. https://www.jove.com/video/52/dissection-of-drosophila-ovaries
  71. Zarco-Fernández S, García-García A, Sanz-Landaluze J, Pecheyran C, Muñoz-Olivas R (2017) In vivo bioconcentration of a metal mixture by Danio rerio eleutheroembryos. Chemosphere 196:87–94.  https://doi.org/10.1016/j.chemosphere.2017.12.141 CrossRefGoogle Scholar
  72. Zarnescu O (2009) Tracing the accumulation and effects of mercury uptake in the previtellogenic ovary of crucian carp, Carassius auratus gibelio by autometallography and caspase-3 immunohistochemistry. Histol Histopathol 24:141–148.  https://doi.org/10.14670/hh-24.141 CrossRefGoogle Scholar
  73. Zhang YF, Chen SY, Qu MJ, Adeleye AO, Di YN (2017) Utilization of isolated marine mussel cells as an in vitro model to assess xenobiotics induced genotoxicity. Toxicol in Vitro 44:219–229.  https://doi.org/10.1016/j.tiv.2017.05.018 CrossRefGoogle Scholar
  74. Zhou Y, Fu XM, He DL, Zou XM, Wu CQ, Guo WZ, Feng W (2016) Evaluation of urinary metal concentrations and sperm DNA damage in infertile men from an infertility clinic. Environ Toxicol Pharmacol 45:68–73.  https://doi.org/10.1016/j.etap.2016.05.020 CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Genotoxicología Ambiental, Departamento de Ciencias Ambientales, Centro de Ciencias de la AtmósferaUniversidad Nacional Autónoma de MéxicoMexicoMexico
  2. 2.Centre de Biologie Intégrative (CBI)-CBDUMR5547 CNRS/Université Toulouse IIIToulouseFrance

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