Abstract
The biological effects of fluoride on human health are often extensive, either beneficial or detrimental. Among the various effects of fluoride exposure in different organs, the reproductive tract is particularly susceptible to disruption by fluoride at a sufficient concentration. It has attracted much attention to the effect of sodium fluoride on male fertility, gestational female, and offspring. Herein, we applied a widespread natural compound sodium fluoride (NaF) and investigated the effects of acute NaF exposure on Leydig cells, including their proliferation, apoptosis, and signal pathway changes. Our results demonstrated that high dosage of NaF could inhibit cell proliferation by stress-induced apoptosis, which was confirmed by cellular and molecular evidences. We found that fluoride exposure affected the expression levels of stress response factors, signal transduction components, and apoptosis-related proteins, including caspase-3/caspase-9, B-cell lymphoma 2 (Bcl-2), and Bax. This study suggests that the complex effects of fluoride on Leydig cells are closely related to its dosage.
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References
Alonso Á, Camargo J (2011) Toxic effects of fluoride ion on survival, reproduction and behaviour of the aquatic snail Potamopyrgus antipodarum (Hydrobiidae, Mollusca). Water Air Soil Pollut 219:81–90
Anarudha CD, Kanno S, Hirano S (2000) Fluoride induces apoptosis by caspase-3 activation in human leukemia HL-60 cells. Arch Toxicol 74:226–230
Ayoob S, Gupta A (2006) Fluoride in drinking water: a review on the status and stress effects. Crit Rev Environ Sci Technol 55:433–487
Barbier O, Arreola-Mendoza L, Del Razo LM (2010) Molecular mechanisms of fluoride toxicity. Chem Biol Interact 188:319–333
Bhat GK, Sea TL, Olatinwo MO, Simorangkir D, Ford GD, Ford BD, Mann DR (2006) Influence of a leptin deficiency on testicular morphology, germ cell apoptosis, and expression levels of apoptosis-related genes in the mouse. J Androl 27:302–310
Chachra D, Limeback H, Willett TL, Grynpas MD (2010) The long-term effects of water fluoridation on the human skeleton. J Dent Res 89:1219–1223
Chinoy NJ, Narayana MV (1994) In vitro fluoride toxicity in human spermatozoa. Reprod Toxicol 8:155–159
Dhar V, Bhatnagar M (2009) Physiology and toxicity of fluoride. Indian J Dent Res 20:350–355
Flora SJ, Mittal M, Mishra D (2009) Co-exposure to arsenic and fluoride on oxidative stress, glutathione linked enzymes, biogenic amines and DNA damage in mouse brain. J Neurol Sci 285:198–205
Ge Y, Niu R, Zhang J, Wang J (2011) Proteomic analysis of brain proteins of rats exposed to high fluoride and low iodine. Arch Toxicol 85:27–33
Halvari AM, Halvari H, Bjørnebekk G, Deci E (2012) Motivation for dental home care: testing a self-determination theory model. J Appl Soc Psychol 42:1–39
Ismail AI, Hasson H (2008) Fluoride supplements, dental caries and fluorosis: a systematic review. J Am Dent Assoc 139:1457–1468
Kumar N, Sood S, Arora B, Singh M, Beena (2010) Effect of duration of fluoride exposure on the reproductive system in male rabbits. J Hum Reprod Sci 3:148–152
Lee JH, Jung JY, Jeong YJ, Park JH, Yang KH, Choi NK, Kim SH, Kim WJ (2008) Involvement of both mitochondrial- and death receptor-dependent apoptotic pathways regulated by Bcl-2 family in sodium fluoride-induced apoptosis of the human gingival fibroblasts. Toxicology 243:340–347
Long H, Jin Y, Lin M, Sun Y, Zhang L, Clinch CA (2003) Fluoride toxicity in the male reproductive system. Fluoride 42(4):260–276
Oncü M, Kocak A, Karaoz E, Darici H, Savik E, Gultekin F (2007) Effect of long-term fluoride exposure on lipid peroxidation and histology of testes in first- and second-generation rats. Biol Trace Elem Res 118:260–268
Reddy PS, Pushpalatha T, Reddy PS (2007) Suppression of male reproduction in rats after exposure to sodium fluoride during early stages of development. Naturwissenschaften 94:607–611
Sun Z, Niu R, Wang B, Jiao Z, Wang J, Zhang J, Wang S, Wang J (2011) Fluoride-induced apoptosis and gene expression profiling in mice sperm in vivo. Arch Toxicol 85:1441–1452
Trevors JT, Saier MH Jr (2009) Where is the global environmental bailout? Water Air Soil Pollut 198:1–3
Yan X, Feng C, Chen Q, Li W, Wang H, Lv L, Smith GW, Wang J (2009) Effects of sodium fluoride treatment in vitro on cell proliferation, apoptosis and caspase-3 and caspase-9 mRNA expression by neonatal rat osteoblasts. Arch Toxicol 83:451–458
Acknowledgments
The project was supported by the Key Project of the Department of Medical and Technology of Shan Xi Province, China (No. 2011080). This research was sponsored by the China National Natural Science Foundation (Grant No. 31240009), Shanxi Scholarship Council of China (Grant No. 2012-079), and the Shanxi Province Science and Technology Bureau Program (Grant No. 2011021030-1).
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Song, G., Wang, R.L., Chen, Z.Y. et al. Toxic effects of sodium fluoride on cell proliferation and apoptosis of Leydig cells from young mice. J Physiol Biochem 70, 761–768 (2014). https://doi.org/10.1007/s13105-014-0344-1
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DOI: https://doi.org/10.1007/s13105-014-0344-1