title: Reproductive dysfunction after mercury exposure at low levels: evidence for a role of glutathione peroxidase (GPx) 1 and GPx4 in male rats.
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 4.6µgkg-1, subsequent doses 0.07µgkg-1day-1) resulted in mean (±s.e.m.) blood mercury concentrations of 6.8±0.3ngmL-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.
authors.affiliation: 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.
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Martinez
authors.affiliation: 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.
authors.forename: Franck M
authors.initials: FM
authors.lastname: Peçanha
authors.affiliation: 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.
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Brum
authors.affiliation: 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.
authors.forename: Francielli W
authors.initials: FW
authors.lastname: Santos
authors.affiliation: 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.
authors.forename: Jeferson L
authors.initials: JL
authors.lastname: Franco
authors.affiliation: 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.
authors.forename: Ana Paula P
authors.initials: APP
authors.lastname: Zemolin
authors.affiliation: Department of Physiology, School of Medicine, Universidade de São Paulo, Av. do Café s/n, 14040904, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Janete A
authors.initials: JA
authors.lastname: Anselmo-Franci
authors.affiliation: 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.
authors.forename: Fernando B
authors.initials: FB
authors.lastname: Junior
authors.affiliation: Department of Biochemistry, Physiology and Molecular Genetics, Universidad Rey Juan Carlos, Avda. Atenas s/n, 28922, Alcorcón, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Alonso
authors.affiliation: Department of Pharmacology, School of Medicine, Universidad Autónoma de Madrid, Arzobispo Morcillo 4, 28029, Madrid, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Salaices
authors.affiliation: Department of Physiological Sciences, Universidade Federal do Espírito Santo, Av. Marechal Campos 1468, 29040-090, Vitória, Espírito Santo, Brazil.
authors.forename: Dalton V
authors.initials: DV
authors.lastname: Vassallo
authors.affiliation: 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.
authors.forename: Fábio G
authors.initials: FG
authors.lastname: Leivas
authors.affiliation: 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.
authors.forename: Giulia A
authors.initials: GA
authors.lastname: Wiggers
mesh_terms: D000818:Animals; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism*; D008297:Male; D008628:Mercury / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013081:Sperm Motility / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism; D013737:Testis / Q000187:drug effects* / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D008628:Mercury; D005978:Glutathione