Decreased in vitro fertility in male rats exposed to fluoride-induced oxidative stress damage and mitochondrial transmembrane potential loss

Izquierdo-Vega, Jeannett A.; Sánchez-Gutiérrez, Manuel; Razo, Luz M. Del

doi:10.1016/j.taap.2008.03.008

Cited by 105 publications

(58 citation statements)

References 35 publications

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“…Moreover, the transmissible germ-cell mutations might exist in the absence of any warning morphological indicator such as abnormal sperm (de Boer et al 1976). Izquierdo-Vega et al (2008) reported an increase in the oxidative stress and loss of mitochondrial transmembrane potential in spermatozoa of male rats receiving NaF doses similar to the ones used in the present study, which could lead to reduced fertility but not morphological changes. It is important to correlate fluoride doses and serum fluoride levels in animal experiments with the real levels of exposure of different populations (Spittle 2008).…”

Section: Discussionmentioning

confidence: 56%

“…Studies have shown no impairment on spermatogenesis (Sprando et al 1998) or adverse effect on reproduction in male rats treated with sodium fluoride (NaF) (Collins et al 2001). However, there are evidences that fluoride intake may cause diminished sperm and lower reproductive hormone levels, leading to a reduced fertility in male rats, receiving NaF (Chinoy et al 1995;Izquierdo-Vega et al 2008). Moreover, other effects like decline in sperm density and sperm viability, increase in sperm abnormalities, testicular histological alterations, were detected in male rats exposed to 150 ppm NaF (Liu et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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Sodium fluoride does not alter sperm production or sperm morphology in rats

Chioca

Müller

Boareto

et al. 2012

Braz. arch. biol. technol.

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The aim of the present study was to evaluate the effects of sodium fluoride (NaF) on the male reproductive system. Adult male rats were exposed to NaF in drinking water for 30 days at three concentrations: 1.54 (control, tap water), 50 and 100 ppm. Body and organ weights, daily sperm production, sperm number and morphology were investigated. No difference was observed on the sperm number and morphology among the groups, as well as body weight and organ absolute and relative weights. Overall, despite the presence of a mild degree of dental fluorosis in the higher dose group, the results indicated that exposure to NaF at the doses used in the present study did not adversely affect sperm production and morphology of male rats.

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Section: Discussionmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Sodium fluoride does not alter sperm production or sperm morphology in rats

Chioca

Müller

Boareto

et al. 2012

Braz. arch. biol. technol.

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“…We showed that the addition of NaF to spermatozoa leads to a significant dose-dependent reduction in capacitation and suppression of the acrosome reaction ( Fig. 3A and B Izquierdo-Vega et al, 2008;Spittle, 2009;Sun et al, 2010), the underlining molecular basis has not been clearly elucidated. Previously published studies demonstrated that the capacitation comprises of an initial bicarbonate-mediated activation of sperm motility; however, the late stages include intracellular alkalinization, increase in protein tyrosine phosphorylation, activation of PKA activity, and preparation for the acrosome reaction (Visconti, 2009;Kwon et al, 2014a).…”

Section: Discussionmentioning

confidence: 94%

“…Sodium fluoride (NaF) was shown to elicit physiological effects in numerous clinical and laboratory studies, with the toxicity of NaF decreasing fertility in most animal species tested (Freni, 1994;Ortiz-P erez et al, 2003;Lu et al, 2014). An intensive literature search revealed that fluoride negatively affects sperm function, including morphology, motility, capacitation, and the acrosome reaction (Chinoy et al, 1994;Elbetieha et al, 2000;Pushpalatha et al, 2005; Dvora 0 kova 0 -Hortova 0 et al Izquierdo-Vega et al, 2008;Spittle, 2009;Sun et al, 2010) all of which are the key process in fertilization, both in vitro and in vivo Kwon et al, 2014a). Additionally, according to National Research Council annual report (ShraderFrechette, 2007), fluoride is an endocrine disruptor altering normal endocrine functions thus might affect sperm function by binding to its receptors on spermatozoa.…”

Section: Introductionmentioning

confidence: 99%

Effect of sodium fluoride on male mouse fertility

et al. 2015

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SUMMARYSodium fluoride (NaF), an environmental pollutant, has been tested for its impact on fertility in several species of laboratory animals. A literature demonstrated that NaF adversely affects sperm motility, morphology, capacitation, and the acrosome reaction. However, the molecular mechanisms underlying these alterations have not yet been elucidated. Therefore, present study was designed to evaluate the regulatory pathways involved in the effect of NaF on sperm function and fertilization. In this in vitro study, mouse spermatozoa were incubated with a range of concentrations (2.5, 5, and 10 mM) of NaF for 90 min in media that support in vitro fertilization. Our results showed that NaF was associated with reduced intracellular ATP generation, motility, and motion kinematics. Likewise, short-term exposure of spermatozoa to NaF significantly reduced the intracellular calcium concentration, protein kinase-A activity, and tyrosine phosphorylation of sperm proteins, which were associated with a significant decrease in the rate of capacitation and the acrosome reaction. Finally, NaF significantly reduced the fertilization and blastocyst formation during early embryonic development. On the basis of these results, we propose that NaF reduces sperm motility, capacitation, and the acrosome reaction leading to poor fertilization and suppressed embryonic development.

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“…• O 2 − was demonstrated in the spermatozoa of rats administered 5 mg F/kg of body weight [99,100] and mouse pancreatic β-cells exposed to 1.35-2.26 mM F [101]. In contrast,…”

Section: 1mentioning

confidence: 94%

Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic Fluoride

2012

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Fluoride (F) is ubiquitous natural substance and widespread industrial pollutant. Although low fluoride concentrations are beneficial for normal tooth and bone development, acute or chronic exposure to high fluoride doses results in adverse health effects. The molecular mechanisms underlying fluoride toxicity are different by nature. Fluoride is able to stimulate G-proteins with subsequent activation of downstream signal transduction pathways such as PKA-, PKC-, PI3-kinase-, Ca 2+ -, and MAPK-dependent systems. G-protein-independent routes include tyrosine phosphorylation and protein phosphatase inhibition. Along with other toxic effects, fluoride was shown to induce oxidative stress leading to excessive generation of ROS, lipid peroxidation, decrease in the GSH/GSSH ratio, and alterations in activities of antioxidant enzymes, as well as to inhibit glycolysis thus causing the depletion of cellular ATP and disturbances in cellular metabolism. Fluoride triggers the disruption of mitochondria outer membrane and release of cytochrome c into cytosol, what activates caspases-9 and -3 (intrinsic) apoptotic pathway. Extrinsic (death receptor) Fas/FasL-caspase-8 and -3 pathway was also described to be implicated in fluoride-induced apoptosis. Fluoride decreases the ratio of antiapoptotic/proapoptotic Bcl-2 family proteins and upregulates the expression of p53 protein. Finally, fluoride changes the expression profile of apoptosis-related genes and causes endoplasmic reticulum stress leading to inhibition of protein synthesis.

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Decreased in vitro fertility in male rats exposed to fluoride-induced oxidative stress damage and mitochondrial transmembrane potential loss

Cited by 105 publications

References 35 publications

Sodium fluoride does not alter sperm production or sperm morphology in rats

Sodium fluoride does not alter sperm production or sperm morphology in rats

Effect of sodium fluoride on male mouse fertility

Molecular Mechanisms of Cytotoxicity and Apoptosis Induced by Inorganic Fluoride

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