Reproductive dysfunction after mercury exposure at low levels: evidence for a role of glutathione peroxidase (GPx) 1 and GPx4 in male rats
Caroline S. Martinez A , Franck M. Peçanha A , Daniela S. Brum A , Francielli W. Santos A , Jeferson L. Franco A , Ana Paula P. Zemolin A , Janete A. Anselmo-Franci B , Fernando B. Junior C , María J. Alonso D , Mercedes Salaices E , Dalton V. Vassallo F , Fábio G. Leivas A and Giulia A. Wiggers A G
+ Author Affiliations
- Author Affiliations
A Postgraduate Program in Biochemistry, Postgraduate Program in Animal Science and Postgraduate Program in Biological Science, Universidade Federal do Pampa, BR 472 – Km 592 –118, 97500-970 Uruguaiana, Rio Grande do Sul, Brazil.
B Department of Physiology, School of Medicine, Universidade de São Paulo, Av. do Café s/n, 14040904, Ribeirão Preto, São Paulo, Brazil.
C Department of Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, 14049-903, Ribeirão Preto, São Paulo, Brazil.
D Department of Biochemistry, Physiology and Molecular Genetics, Universidad Rey Juan Carlos, Avda. Atenas s/n, 28922, Alcorcón, Spain.
E Department of Pharmacology, School of Medicine, Universidad Autónoma de Madrid, Arzobispo Morcillo 4, 28029, Madrid, Spain.
F Department of Physiological Sciences, Universidade Federal do Espírito Santo, Av. Marechal Campos 1468, 29040-090, Vitória, Espírito Santo, Brazil.
G Corresponding author. Email: giuliawp@gmail.com
Reproduction, Fertility and Development 29(9) 1803-1812 https://doi.org/10.1071/RD16310
Submitted: 16 April 2016 Accepted: 22 September 2016 Published: 19 October 2016
Abstract
Mercury is a ubiquitous environmental pollutant and mercury contamination and toxicity are serious hazards to human health. Some studies have shown that mercury impairs male reproductive function, but less is known about its effects following exposure at low doses and the possible mechanisms underlying its toxicity. Herein we show that exposure of rats to mercury chloride for 30 days (first dose 4.6 µg kg–1, subsequent doses 0.07 µg kg–1 day–1) resulted in mean (± s.e.m.) blood mercury concentrations of 6.8 ± 0.3 ng mL–1, similar to that found in human blood after occupational exposure or released from removal of amalgam fillings. Even at these low concentrations, mercury was deposited in reproductive organs (testis, epididymis and prostate), impaired sperm membrane integrity, reduced the number of mature spermatozoa and, in the testes, promoted disorganisation, empty spaces and loss of germinal epithelium. Mercury increased levels of reactive oxygen species and the expression of glutathione peroxidase (GPx) 1 and GPx4. These results suggest that the toxic effects of mercury on the male reproductive system are due to its accumulation in reproductive organs and that the glutathione system is its potential target. The data also suggest, for the first time, a possible role of the selenoproteins GPx1 and GPx4 in the reproductive toxicity of mercury chloride.
Additional keywords: glutathione system, heavy metal, oxidative stress, reproductive toxicity.
References
Aitken, R. J. (1995). Free radicals, lipid peroxidation and sperm function. Reprod. Fertil. Dev. 7, 659–668.| Free radicals, lipid peroxidation and sperm function.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28Xht1Clsrw%3D&md5=abd4f936469db218ee492eb32109415fCAS | 8711202PubMed |
Alvarez, J. G., and Storey, B. T. (1989). Role of glutathione peroxidase in protecting mammalian spermatozoa from loss of motility caused by spontaneous lipid peroxidation. Gamete Res. 23, 77–90.
| Role of glutathione peroxidase in protecting mammalian spermatozoa from loss of motility caused by spontaneous lipid peroxidation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1MXksFCrt74%3D&md5=af762cdaf86b123da120c1f74dfb14afCAS | 2545584PubMed |
Alvarez, J. G., Touchstone, J. C., Blasco, L., and Storey, B. T. (1987). Spontaneous lipid peroxidation and production of hydrogen peroxide and superoxide in human spermatozoa. Superoxide dismutase as major enzyme protectant against oxygen toxicity. J. Androl. 8, 338–348.
| Spontaneous lipid peroxidation and production of hydrogen peroxide and superoxide in human spermatozoa. Superoxide dismutase as major enzyme protectant against oxygen toxicity.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2sXmtFGhtb4%3D&md5=6454ac07b802bad44f3dd131995a1190CAS | 2822642PubMed |
Batista, B. L., Grotto, D., Rodrigues, J. L., Oliveira, V., and Barbosa, F. (2009). Determination of trace elements in biological samples by inductively coupled plasma mass spectrometry (ICP-MS) with tetramethylammonium hydroxide solubilization at room temperature. Anal. Chim. Acta 646, 23–29.
| Determination of trace elements in biological samples by inductively coupled plasma mass spectrometry (ICP-MS) with tetramethylammonium hydroxide solubilization at room temperature.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXntlSnurY%3D&md5=10376d66dc4954401cf534346eed1554CAS | 19523552PubMed |
Benov, L. C., Benchev, I. C., and Monovich, O. H. (1990). Thiol antidotes effect on lipid peroxidation in mercury-poisoned rats. Chem. Biol. Interact. 76, 321–332.
| Thiol antidotes effect on lipid peroxidation in mercury-poisoned rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3MXlslWhuw%3D%3D&md5=f5c2cf1687240e713a00b745616b53a8CAS | 2225233PubMed |
Björkman, L., Sandborgh-Englund, G., and Ekstrand, J. (1997). Mercury in saliva and feces after removal of amalgam fillings. Toxicol. Appl. Pharmacol. 144, 156–162.
| Mercury in saliva and feces after removal of amalgam fillings.Crossref | GoogleScholarGoogle Scholar | 9169079PubMed |
Boujbiha, M. A., Hamden, K., Guermazi, F., Bouslama, A., Omezzine, A., Kammoun, A., and El Feki, A. (2009). Testicular toxicity in mercuric chloride treated rats: association with oxidative stress. Reprod. Toxicol. 28, 81–89.
| Testicular toxicity in mercuric chloride treated rats: association with oxidative stress.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXms1Kmtbo%3D&md5=6fe70bbe984e2049c0bc8f938f72e0d7CAS | 19427169PubMed |
Boujbiha, M. A., Hamden, K., Guermazi, F., Bouslama, A., Omezzine, A., and El Feki, A. (2011). Impairment of spermatogenesis in rats by mercuric chloride: involvement of low 17β-estradiol level in induction of acute oxidative stress. Biol. Trace Elem. Res. 142, 598–610.
| Impairment of spermatogenesis in rats by mercuric chloride: involvement of low 17β-estradiol level in induction of acute oxidative stress.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXpvFWisbg%3D&md5=42b67028c91b272e4ed01ea1909f45a4CAS | 20820944PubMed |
Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principles of protein–dye binding. Anal. Biochem. 72, 248–254.
| 1:CAS:528:DyaE28XksVehtrY%3D&md5=def289bee4247ee0e8f8ebf79062a762CAS | 942051PubMed |
Carlberg, I., and Mannervik, B. (1985). Glutathione reductase from rat liver. Methods Enzymol. 113, 484–490.
| Glutathione reductase from rat liver.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL28XkslCqsQ%3D%3D&md5=446d0f3cc4534010f194b6bb419366f5CAS | 3003504PubMed |
Carlsen, E., Giwercman, A., Keiding, N., and Skakkebaek, N. E. (1992). Evidence for decreasing quality of semen during past 50 years. BMJ 305, 609–613.
| Evidence for decreasing quality of semen during past 50 years.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3s%2Fgs1Citw%3D%3D&md5=807daf25177d44cc1230da3d02f7fda4CAS | 1393072PubMed |
Carmignani, M., Boscolo, P., Artese, L., Del Rosso, G., Porcinelli, G., Porcelli, G., Felaco, M., Volpe, A. R., and Giuliano, G. (1992). Renal mechanisms in the cardiovascular effects of chronic exposure to inorganic mercury rats. Br. J. Ind. Med. 49, 226–232.
| 1:CAS:528:DyaK38XktVagur0%3D&md5=cad0cfae8bcbeac1115e0a6b45264688CAS | 1571292PubMed |
Chen, C., Qu, L., Li, B., Xing, L., Jia, G., Wang, T., Gao, Y., Zhang, P., Li, M., Chen, W., and Chai, Z. (2005). Increased oxidative DNA damage, as assessed by urinary 8-hydroxy-2′-deoxyguanosine concentrations, and serum redox status in persons exposed to mercury. Clin. Chem. 51, 759–767.
| Increased oxidative DNA damage, as assessed by urinary 8-hydroxy-2′-deoxyguanosine concentrations, and serum redox status in persons exposed to mercury.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXivFCqtLg%3D&md5=e65402f8e8aced0ac1755a63f6aa2504CAS | 15695327PubMed |
Choy, C. M., Lam, C. W., Cheung, L. T., Briton-Jones, C. M., Cheung, L. P., and Haines, C. J. (2002). Infertility, blood mercury concentrations and dietary seafood consumption: a case control study. BJOG 109, 1121–1125.
| 1:CAS:528:DC%2BD38XnsVWltb8%3D&md5=721e0aecbb543952034a94b167c9e4ebCAS | 12387464PubMed |
Cole, D. C., Wainman, B., Sanin, L. H., Weber, J. P., Muggah, H., and Ibrahim, S. (2006). Environmental contaminant levels and fecundability among non-smoking couples. Reprod. Toxicol. 22, 13–19.
| Environmental contaminant levels and fecundability among non-smoking couples.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XmsFSkt7Y%3D&md5=e707f4512e036f77d858b818061848faCAS | 16439098PubMed |
Drevet, J. R. (2006). The antioxidant glutathione peroxidase family and spermatozoa: a complex story. Mol. Cell. Endocrinol. 250, 70–79.
| The antioxidant glutathione peroxidase family and spermatozoa: a complex story.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XksVGjt78%3D&md5=7113622d9f7bc095dd895ab15f98d27cCAS | 16427183PubMed |
Durak, D., Kalender, S., Uzun, F. G., Demir, F., and Kalender, Y. (2010). Mercury chloride-induced oxidative stress and the protective effect of vitamins C and E in human erythrocytes in vitro. Afr. J. Biotechnol. 9, 488–495.
| 1:CAS:528:DC%2BC3cXhsFGrur8%3D&md5=a4dcf16a8d36ffa701b803aa70d349f4CAS |
El-Desoky, G. E., Bashandy, S. A., Alhazza, I. M., Al-Othman, Z. A., Aboul-Soud, M. A. M., and Yusuf, K. (2013). Improvement of mercuric chloride-induced testis injuries and sperm quality deteriorations by Spirulina platensis in rats. PLoS One 8, e59177.
| Improvement of mercuric chloride-induced testis injuries and sperm quality deteriorations by Spirulina platensis in rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXmtVent70%3D&md5=ff2d9d1c982ec2d9230d88ee35440bfdCAS | 23555627PubMed |
Farina, M., Campos, F., Vendrell, I., Berenguer, J., Barzi, M., Pons, S., and Suñol, C. (2009). Probucol increases glutathione peroxidase-1 activity and displays long-lasting protection against methylmercury toxicity in cerebellar granule cells. Toxicol. Sci. 112, 416–426.
| Probucol increases glutathione peroxidase-1 activity and displays long-lasting protection against methylmercury toxicity in cerebellar granule cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhsVajur3N&md5=2decab87434596fdbad30bce0d294162CAS | 19770487PubMed |
Foresta, C., Flohé, L., Garolla, A., Roveri, A., Ursini, F., and Maiorino, M. (2002). Male infertility is linked to the selenoprotein phospholipid hydroperoxide glutathione peroxidase. Biol. Reprod. 67, 967–971.
| Male infertility is linked to the selenoprotein phospholipid hydroperoxide glutathione peroxidase.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XmsV2jtro%3D&md5=479636bd9ce70210d80af64f34ae0ee4CAS | 12193409PubMed |
Franco, J. L., Posser, T., Dunkley, P. R., Dickson, P. W., Dickson, P. W., Mattos, J. J., Martins, R., Bainy, A. C., Marques, M. R., Dafre, A. L., and Farina, M. (2009). Methylmercury neurotoxicity is associated with inhibition of the antioxidant enzyme glutathione peroxidase. Free Radic. Biol. Med. 47, 449–457.
| Methylmercury neurotoxicity is associated with inhibition of the antioxidant enzyme glutathione peroxidase.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXotl2ltrs%3D&md5=acf345d3c6288b736ead69ddd8d58be8CAS | 19450679PubMed |
Habig, W. H., Pabst, M. J., and Jakoby, W. B. (1974). Glutathione S-transferases: the first enzymatic step in mercapturic acid formation. J. Biol. Chem. 249, 7130–7139.
| 1:CAS:528:DyaE2MXltlahtg%3D%3D&md5=b6fc6b72590e1c52ffbce9a8ee9086ffCAS | 4436300PubMed |
Halliwell, B., and Whiteman, M. (2004). Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br. J. Pharmacol. 142, 231–255.
| Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean?Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXkvVyks7w%3D&md5=29baa499bc7bca271e7c2ad2c1ff5beeCAS | 15155533PubMed |
Hansen, J. M., Zhang, H., and Hones, D. P. (2006). Differential oxidation of thio-redoxin-1, thioredoxin-2, and glutathione by metal ions. Free Radic. Biol. Med. 40, 138–145.
| Differential oxidation of thio-redoxin-1, thioredoxin-2, and glutathione by metal ions.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtlSiu73J&md5=2fd45649cf3edc70d53a0b24191c9717CAS | 16337887PubMed |
Hissin, P. J., and Hilf, R. (1976). A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal. Biochem. 74, 214–226.
| A fluorometric method for determination of oxidized and reduced glutathione in tissues.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE28XkslCntL0%3D&md5=a88f72b03ff724a44dda95f6c4953fedCAS | 962076PubMed |
Homma-Takeda, S., Kugenuma, Y., Iwamuro, T., Kumagai, Y., and Shimojo, N. (2001). Impairment of spermatogenesis in rats by methylmercury: involvement of stage- and cell- specific germ cell apoptosis. Toxicology 169, 25–35.
| Impairment of spermatogenesis in rats by methylmercury: involvement of stage- and cell- specific germ cell apoptosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXotFSmtbk%3D&md5=fe9742c7d7bdf282c218f05e81dd2730CAS | 11696407PubMed |
Imai, H., Suzuki, K., Ishizaka, K., Ichinose, S., Oshima, H., Okayasu, I., Emoto, K., Umeda, M., and Nakagawa, Y. (2001). Failure of the expression of phospholipid hydroperoxide glutathione peroxidase in the spermatozoa of human infertile males. Biol. Reprod. 64, 674–683.
| Failure of the expression of phospholipid hydroperoxide glutathione peroxidase in the spermatozoa of human infertile males.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXnsVOgtw%3D%3D&md5=ad8201d94a24eb68ce43f4cc0f500eefCAS | 11159372PubMed |
Kalender, S., Uzun, F. G., Demir, F., Uzunhisarcıklı, M., and Aslanturk, A. (2013). Mercuric chloride-induced testicular toxicity in rats and the protective role of sodium selenite and vitamin E. Food Chem. Toxicol. 55, 456–462.
| Mercuric chloride-induced testicular toxicity in rats and the protective role of sodium selenite and vitamin E.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXktlOhsb4%3D&md5=c6f5b2ee07e63a999e7ab92a5b1215b5CAS | 23369933PubMed |
Kasraei, S. , Mortazavi, H., Vahedi, M., Bakianian Vaziri, P., and Assary, M. (2010). Blood mercury level and its determinants among dental practitioners in Hamadan. J. Dent. (Tehran) 7, 55–63.
Keck, C., Bergman, M., Ernst, E., Muller, C., Kliensch, S., and Nieschlag, E. (1993). Autometallographic detection of mercury in testicular tissue of an infertile man exposed to mercury vapour. Reprod. Toxicol. 7, 469–475.
| Autometallographic detection of mercury in testicular tissue of an infertile man exposed to mercury vapour.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2cXht1OjsLc%3D&md5=0f3227ab139ee74810dfdeacaf368becCAS | 8274823PubMed |
Khan, A. T., Atkinson, A., Graham, T. C., Thompson, S. J., Ali, S., and Shireen, K. F. (2004). Effects of inorganic mercury on reproductive performance of mice. Food Chem. Toxicol. 42, 571–577.
| Effects of inorganic mercury on reproductive performance of mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhslSqtrk%3D&md5=4c6f5e34c93be4a8bbac28e0e014cce5CAS | 15019180PubMed |
Kobal, A. B., Prezelj, M., Horvat, M., Krsnik, M., Gibicar, D., and Osredkar, J. (2008). Glutathione level after long-term occupational elemental mercury exposure. Environ. Res. 107, 115–123.
| Glutathione level after long-term occupational elemental mercury exposure.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXkvVOitL8%3D&md5=c0385b7c2959d5e861614152cf211efcCAS | 17706633PubMed |
Liang, P., Qin, Y. Y., Zhang, C., Zhang, J., Cao, Y., Wu, S. C., Wong, C. K., and Wong, M. H. (2013). Plasma mercury levels in Hong Kong residents: in relation to fish consumption. Sci. Total Environ. 463-464, 1225–1229.
| Plasma mercury levels in Hong Kong residents: in relation to fish consumption.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXnsFGhurY%3D&md5=f9baf52bfdd5fe5224e21726dc6709a1CAS | 23680090PubMed |
Lin, Y. S., Ginsberg, G., Lin, J. W., and Sonawane, B. (2014). Mercury exposure and omega-3 fatty acid intake in relation to renal function in the US population. Int. J. Hyg. Environ. Health 217, 465–472.
| Mercury exposure and omega-3 fatty acid intake in relation to renal function in the US population.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhslaitL%2FP&md5=2bd76c7d8737f6f44b4f1e24baa5eb86CAS | 24189320PubMed |
Loetchutinat, C., Kothan, S., Dechsupa, S., Meesungnoen, J., Jay-Gerin, J., and Mankhetkorn, S. (2005). Spectrofluorometric determination of intracellular levels of reactive oxygen species in drug-sensitive and drug-resistant cancer cells using the 2′,7′-dichlorofluorescein diacetate assay. Radiat. Phys. Chem. 72, 323–331.
| Spectrofluorometric determination of intracellular levels of reactive oxygen species in drug-sensitive and drug-resistant cancer cells using the 2′,7′-dichlorofluorescein diacetate assay.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhtVamtLzF&md5=7b6d03d52d955a88154ff11ea89890dcCAS |
Lomeo, A. M., and Giambersio, A. M. (1991). Water-test: a simple method to assess sperm-membrane integrity. Int. J. Androl. 14, 278–282.
| Water-test: a simple method to assess sperm-membrane integrity.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3MzkvV2isQ%3D%3D&md5=8f9e042f25374f6b2dff0ac14cf27b2bCAS | 1879962PubMed |
Martinez, C. S., Escobar, A. G., Torres, J. G. D., Brum, D. S., Santos, F. W., Alonso, M. J., Salaices, M., Vassallo, D. V., Peçanha, F. M., Leivas, F. G., and Wiggers, G. A. (2014a). Chronic exposure to low doses of mercury impairs sperm quality and induces oxidative stress in rats. J. Toxicol. Environ. Health A 77, 143–154.
| Chronic exposure to low doses of mercury impairs sperm quality and induces oxidative stress in rats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXjtVGnurc%3D&md5=4e960322975b50b92c0c1c3922f455dbCAS | 24555655PubMed |
Martinez, C. S., Torres, J. G. D., Peçanha, F. M., Anselmo-Franci, J. A., Vassallo, D. V., Salaices, M., Alonso, M. J., and Wiggers, G. A. (2014b). 60-Day chronic exposure to low concentrations of HgCl2 impairs sperm quality: hormonal imbalance and oxidative stress as potential routes for reproductive dysfunction in rats. PLoS One 9, e111202.
| 60-Day chronic exposure to low concentrations of HgCl2 impairs sperm quality: hormonal imbalance and oxidative stress as potential routes for reproductive dysfunction in rats.Crossref | GoogleScholarGoogle Scholar | 25368988PubMed |
McKelvey, W., Gwynn, R. C., Jeffery, N., Kass, D., Thorpe, L. E., Garg, R. K., Palmer, C. D., and Parsons, P. J. (2007). A biomonitoring study of lead, cadmium, and mercury in the blood of New York city adults. Environ. Health Perspect. 115, 1435–1441.
| 1:CAS:528:DC%2BD2sXht1ertrrJ&md5=4e5f9d63e42c8ffb158df9384ab859ccCAS | 17938732PubMed |
Mohamed, M. K., Barbacher, T. M., and Mottet, N. K. (1987). Effects of methylmercury on testicular functions in Macaca fascicularis monkeys. Pharmacol. Toxicol. 60, 29–36.
| Effects of methylmercury on testicular functions in Macaca fascicularis monkeys.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2sXitV2jsbc%3D&md5=1151e68bb5391feef237095b517a79d0CAS | 3562387PubMed |
Moreno, S. G., Laux, G., Brielmeier, M., Bornkamm, G. W., and Conrad, M. (2003). Testis-specific expression of the nuclear form of phospholipid hydroperoxide glutathione peroxidase (PHGPx). Biol. Chem. 384, 635–643.
| Testis-specific expression of the nuclear form of phospholipid hydroperoxide glutathione peroxidase (PHGPx).Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXjvVekuro%3D&md5=fab07e7d2ca331af4022a6fe71a74e74CAS | 12751792PubMed |
National Research Council (NRC) (2000). ‘Toxicological Effects of Methylmercury.’ (National Academy Press: Washington, DC.)
Nelson, C. M., and Bunge, R. G. (1974). Semen analysis: evidence for changing parameters of male fertility potential. Fertil. Steril. 25, 503–507.
| Semen analysis: evidence for changing parameters of male fertility potential.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE2c3lt1Sqtw%3D%3D&md5=17b72d459d1809f87d1e7c43dff45f02CAS | 4835605PubMed |
Nguyen, T., Sherratt, P. J., and Pickett, C. B. (2003). Regulatory mechanisms controlling gene expression mediated by the antioxidant response element. Annu. Rev. Pharmacol. Toxicol. 43, 233–260.
| Regulatory mechanisms controlling gene expression mediated by the antioxidant response element.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXitFWqsbY%3D&md5=0786d210e936198b6fecf537d1518b1aCAS | 12359864PubMed |
Peçanha, F. M., Wiggers, G. A., Briones, A. M., Perez-Giron, J. V., Miguel, M., Garcia-Redondo, A. B., Vassallo, D. V., Alonso, M. J., and Salaices, M. (2010). The role of cyclooxygenase (COX)-2 derived prostanoids on vasoconstrictor responses to phenylephrine is increased by exposure to low mercury concentration. J. Physiol. Pharmacol. 61, 29–36.
| 20228412PubMed |
Popescu, H. I. (1978). Poisoning with alkylmercuric compounds. BMJ 1, 1347.
| Poisoning with alkylmercuric compounds.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE1c7ms1GitQ%3D%3D&md5=9ef600c1bcdb610ef505f34d8610bb66CAS | 647272PubMed |
Queiroz, E. K. R., and Waissmann, W. (2006). Occupational exposure and effects on the male reproductive system. Cad. Saude Publica 22, 485–493.
| Occupational exposure and effects on the male reproductive system.Crossref | GoogleScholarGoogle Scholar |
Ramalingam, V., Vimaladevi, V., Rajeswary, S., and Suryavathi, V. (2003). Effect of mercuric chloride on circulating hormones in adult albino rats. J. Environ. Biol. 24, 401–404.
| 1:CAS:528:DC%2BD3sXotlSntbc%3D&md5=db254ce0e7c9002144d7a95e2b31ebadCAS | 15248653PubMed |
Rao, M. V., and Gangadharan, B. (2008). Antioxidative potential of melatonin against mercury induced intoxication in spermatozoa in vitro. Toxicol. In Vitro 22, 935–942.
| Antioxidative potential of melatonin against mercury induced intoxication in spermatozoa in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXkvFWgt70%3D&md5=9c5d37ab7bc455cd2d7448720e2bc384CAS | 18329842PubMed |
Rao, A. V. S. K., and Shaha, C. (2000). Role of glutathione S-transferases in oxidative stress-induced male germ cell apoptosis. Free Radic. Biol. Med. 29, 1015–1027.
| Role of glutathione S-transferases in oxidative stress-induced male germ cell apoptosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXotVCrurc%3D&md5=37bd0063a0634b1004aca295f5ee999dCAS |
Rao, M. V., and Sharma, P. S. (2001). Protective effect of vitamin E against mercuric chloride reproductive toxicity in male mice. Reprod. Toxicol. 15, 705–712.
| Protective effect of vitamin E against mercuric chloride reproductive toxicity in male mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXovVCgsrc%3D&md5=b93998c4155baac59d483887df943094CAS | 11738524PubMed |
Reeves, M. A., and Hoffmann, P. R. (2009). The human selenoproteome: recent insights into functions and regulation. Cell. Mol. Life Sci. 66, 2457–2478.
| The human selenoproteome: recent insights into functions and regulation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXos1egs7Y%3D&md5=5245caeec43b7ff1f35e8a0a6dbbcd55CAS | 19399585PubMed |
Rice, D. C. (2004). The US EPA reference dose for methylmercury: sources of uncertainty. Environ. Res. 95, 406–413.
| The US EPA reference dose for methylmercury: sources of uncertainty.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXlt1enu78%3D&md5=ca306b1a606b912caf80cd6bcdb36a37CAS | 15220074PubMed |
Sheiner, E. K., Sheiner, E., Hammel, R. D., Potashnik, G., and Carel, R. (2003). Effect of occupational exposures on male fertility: literature review. Ind. Health 41, 55–62.
| Effect of occupational exposures on male fertility: literature review.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXjvVSgtr4%3D&md5=e2336f67ef729552d81815a0935158c6CAS | 12725464PubMed |
Vachhrajani, K. D., Makhija, S., Chinoy, N. J., and Chowdhury, A. R. (1988). Structural and functional alterations in testis of rats after mercuric chloride treatment. J. Reprod. Bio. Compara. Endocrinol. 8, 97–104.
| 1:CAS:528:DyaL1MXitVOntLY%3D&md5=61c410fb8061f07fc3a60529847779c4CAS |
Wendel, A. (1981). Glutathione peroxidase. Methods Enzymol. 77, 325–333.
| Glutathione peroxidase.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL38XhtFOrur0%3D&md5=72ad85fc3aa00da12abecaa7780e360aCAS | 7329310PubMed |
Wiggers, G. A., Peçanha, F. M., Briones, A. M., Pérez-Girón, J. V., Miguel, M., Vassallo, D. V., Cachofeiro, V., Alonso, M. J., and Salaices, M. (2008). Low mercury concentrations cause oxidative stress and endothelial dysfunction in conductance and resistance arteries. Am. J. Physiol. Heart Circ. Physiol. 295, H1033–H1043.
| Low mercury concentrations cause oxidative stress and endothelial dysfunction in conductance and resistance arteries.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtFCgt7bK&md5=fcd1bbaf745990286e01cec3bbc27d56CAS | 18599595PubMed |
Zemolin, A. P. P., Meinerz, D. F., de Paula, M. T., Mariano, D. O. C., Rocha, J. B., Pereira, A. B., Posser, T., and Franco, J. L. (2012). Evidences for a role of glutathione peroxidase 4 (GPx4) in methylmercury induced neurotoxicity in vivo. Toxicology 302, 60–67.
| Evidences for a role of glutathione peroxidase 4 (GPx4) in methylmercury induced neurotoxicity in vivo.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38Xht1SkurzF&md5=2684782907224b0fe90274296f650044CAS |
