Abstract
We sequenced RNA transcripts from the testicles of healthy male mice, divided into a control group with distilled water and two experimental groups with 50 and 100 mg/l NaF in drinking water for 56 days. Bowtie/Tophat were used to align 50-bp paired-end reads into transcripts, Cufflinks to measure the relative abundance of each transcript and IPA to analyze RNA-Sequencing data. In the 100 mg/l NaF-treated group, four pathways related to IL-17, TGF- and other cellular growth factor pathways were overexpressed. The mRNA expression of IL-17RA, IL-17RC, MAP2K1, MAP2K2, MAP2K3 and MAPKAPK2, monitored by qRT-PCR, increased remarkably in the 100 mg/L NaF group and coincided with the result of RNA-Sequencing. Fluoride exposure could disrupt spermatogenesis and testicles in male mice by influencing many signaling pathways and genes, which work on the immune signal transduction and cellular metabolism. The high expression of the IL-17 signal pathway was a response to the invasion of the testicular immune system due to extracellular fluoride. The PI3-kinase/AKT, MAPKs and the cytokines in TGF- family were contributed to control the IL-17 pathway activation and maintain the immune privilege and spermatogenesis. All the findings provided new ideas for further molecular researches of fluorosis on the reproduction and immune response mechanism.
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Fluoride-elicited developmental testicular toxicity in rats: roles of endoplasmic reticulum stress and inflammatory response
Long-term excessive fluoride intake is known to be toxic and can damage a variety of organs and tissues in the human body. However, the molecular mechanisms underlying fluoride-induced male reproductive toxicity are not well understood. In this study, we used a rat model to simulate the situations of human exposure
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Vitamin E and Lycopene Reduce Coal Burning Fluorosis-induced Spermatogenic Cell Apoptosis via Oxidative Stress-mediated JNK and ERK Signaling Pathways.
Although fluoride has been widely used in toothpaste, mouthwash, and drinking water to prevent dental caries, the excessive intake of fluoride can cause fluorosis which is associated with dental, skeletal, and soft tissue fluorosis. Recent evidences have drawn the attention to its adverse effects on male reproductive system that include
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Fluoride Compromises Testicular Redox Sensor, Gap Junction Protein, and Metabolic Status: Amelioration by Melatonin.
The excess fluoride intake has been shown to adversely affect male reproductive health. The aim of the present study was to investigate the key mechanism underlying fluoride-induced testicular dysfunction and the role of melatonin as a modulator of testicular metabolic, oxidative, and inflammatory load. The present results indicated that sodium
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Abnormal spermatogenesis following sodium fluoride exposure is associated with the downregulation of CREM and ACT in the mouse testis.
cAMP response element modulator (CREM) is involved in regulating gene expression in normal spermatogenesis. The transcriptional activity of CREM is partly regulated by activator of CREM in the testis (ACT). To investigate the effects of different concentrations of sodium fluoride (NaF) on the gene and protein expression of CREM and
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[The protective effects of a-lipoic acid on fluoride-induced reproductive lesion in rats via oxidative stress-mediated endoplasmic reticulum stress]
Objective: To determine the oxidative stress and endoplasmic reticulum stress and their changes after a-lipoic acid (a-LA) intervention, and to explore the effect and mechanism of fluoride-induced reproductive lesion. Methods: A total of 40 male Sprague-Dawley (SD) rats were randomly divided into four groups, control group(0.9% sodium chloride), a-LA group(100 mg/kg
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Fluoride's Effect on Male Reproductive System - Human Studies
Consistent with in vitro and animal research, studies of human populations have reported associations between fluoride exposure and damage to the male reproductive system. Most notably, a scientist at the Food & Drug Administration reported in 1994 that populations in the United States with more than 3 ppm fluoride in their water had lower "total fertility rates" than populations with lower fluoride levels.
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Is the Ingestion of Fluoride an Immunosuppressive Practice?
This paper records several observations which suggest that habitual ingestion of small doses of fluoride, even as small as the 1 mg/L contained in fluoridated water, may decrease the function of the immune system.
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Fluoride's Effect on the Male Reproductive System -- In Vitro Studies
Carefully controlled in vitro studies have found that direct exposure of fluoride to the testes or semen inhibits testosterone production and damages sperm. While researchers have known since the 1930s that mega concentrations of fluoride can completely (but reversibly) immobilize sperm, it was not until the 1970s and 1980s that researchers found that relatively modest concentrations of fluoride could cause damage prior to complete immobilization.
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Does Fluoride Ingestion Affect Developing Immune System Cells?
Considerations, supported by some published experimental evidence, suggest that fluoride released during the resorption of high-fluoride bone may produce detrimental effects not only on bone cells but on developing cells of the immune system.
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Fluoride's Effect on Male Reproductive System -- The "Sprando/Collins" Anomaly
In contrast to the findings of over 60 animal studies from other research teams, a series of studies by FDA researchers Sprando & Collins reported virtually no evidence of reproductive toxicity among animals treated with very high levels of fluoride exposure. The reasons for this discrepancy remains unclear. Excerpts from Sprando/Collins' Studies: "This study
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