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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Fluoride-Induced Sperm Damage and HuR-Mediated Excessive Apoptosis and Autophagy in Spermatocytes.
It is critical to determine the mechanism underlying fluoride (F)-induced damage of the testes to develop appropriate strategies for monitoring and intervention. In the present study, exposure to 50 mg/L sodium fluoride (NaF) for 90 days damaged the normal structure of the testes and quality of the sperm, particularly the spermatocytes, and
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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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Effects of high fluoride on sperm quality and testicular histology in male rats
Sixty-four forty-day old male Wistar rats were divided randomly into two groups of thirty-two each. With one group untreated as controls, the other group was administered 150 mg NaF/L (68 ppm F–) in their drinking water to assess the effects of high fluoride on sperm quality and testicular histology at
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Fluoride exposure alters the ultra-structure of sperm flagellum via reducing key protein expressions in testis.
Highlights Fluoride damaged the typical “9 + 2" microtubule structure of sperm flagellum. Fluoride reduced AKAP3 and AKAP4 expressions related to fibrous sheathes formation. CFAP43, CFAP44 and HYDIN expressions in sperm axoneme were down-regulated by fluoride. Fluoride did not affect Dnah1, Eno4, Spef2, Spag6, Spag16, and Cfap69 expressions in testes. Excessive
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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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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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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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Fluoride & the Immune System - Summation from the US National Research Council (2006)
“There is no question that fluoride can affect the cells involved in providing immune responses. The question is what proportion, if any, of the population consuming drinking water containing fluoride at 4.0 mg/L on a regular basis will have their immune systems compromised? Not a single epidemiologic study has investigated whether fluoride in the drinking water at 4 mg/L is associated with changes in immune function. Nor has any study examined whether a person with an immunodeficiency disease can tolerate fluoride ingestion from drinking water.”
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