Lethal effect of fluoride on male reproductive biology
DOI:
https://doi.org/10.31305/rrijm.2023.v08.n08.037Keywords:
Fluoride, male reproduction, Health hazardAbstract
Fluoride, a naturally occurring element widely used in dental care and water fluoridation programs, has raised increasing concern due to its potential toxic effects on various biological systems, including the male reproductive system. Chronic exposure to elevated fluoride levels has been associated with impaired spermatogenesis, reduced sperm count and motility, and altered testicular histoarchitecture in both human and animal studies. Mechanistically, fluoride toxicity is linked to oxidative stress, mitochondrial dysfunction, endocrine disruption, and apoptosis of germ cells. Fluoride can induce lipid peroxidation and reduce the activity of key antioxidant enzymes such as superoxide dismutase and catalase, leading to cellular damage in testicular tissues. Furthermore, it can interfere with the hypothalamic-pituitary-gonadal axis, resulting in decreased testosterone synthesis and altered expression of reproductive hormones. The degree of reproductive impairment appears to depend on the dose, duration of exposure, and age at exposure. It is able to slow down immunosystem and it also has toxic effect on muscle. Fluoride has several negative impacts on reproduction in several invertebrate and vertebrate organism. Although moderate fluoride intake is considered beneficial for dental health, excessive and prolonged exposure poses a significant threat to male fertility. Further research is needed to clarify the molecular pathways underlying fluoride-induced testicular toxicity and to establish safe exposure limits that protect reproductive health without compromising dental benefits.
References
Akyuz, S., Yarat, A., Alturfan, E.E., Kaya, S. (2015). Fluoride in saliva and its impact on health. In: Preedy VR, editor. Fluorine. London: Royal Society of Chemistry. P. 173-185.
Arends, J., Ten Cate, J.M. (1981). Tooth enamel remineralization. J Crystal Growth., 53:135-147.
Baldini, F., Gabrieli, P., Rogers, D.W., Catteruccia, F., 2012. Function and composition of male accessory gland secretions in Anopheles gambiae: a comparison with other insect vectors of infectious diseases. Pathog. Glob. Health. 106, 82-93. https://doi.org/10.1179/2047773212Y.0000000016
Büyüksönmez, F., Rynk, R., Hess, T.F., Bechinski, E., 2013. Literature Review: Occurrence, Degradation and Fate of Pesticides During Composting: Part II: Occurrence and Fate of Pesticides in Compost and Composting Systems. https://doi.org/10.1080/1065657X.2000.10701751
Chae, G.Y., Yun, S.T., Mayer, B., Kim, K.H., Kim, S.Y., Kwon, J.S., Kim, k., koh, Y.K., 2007. Fluorine geochemistry in bedrock groundwater of South Korea. Sci Total Environ. 385, 272-283.
Chinoy, N.J., Sequeira, E., 1989. Effects of fluoride on the histoarchitecture of reproductive organs of the male mouse. Reproductive Toxicol. 3, 261-267. https://doi.org/10.1016/0890-6238(89)90020-8
de la Fuente., B., M. Vázquez, Rocha, R.A., Devesa, V., Vélez, D. Effects of sodium fluoride on immune response in murine macrophages. Toxicol. in Vitro 34 (2016) 81–87.
Ericsson, Y. (1970). Fluorides and human health, Lancet. 2: 351–352.
Fathpour, H., Noori, A., Zeinali, B., 2007b. Effects of juvenoid pyriproxyfen on reproductive organ, development and reproduction in German cockroach (Dictyoptera: Blattellidae). IRAN. J. SCI. TECHNOL. A. 31, 89-98.
Fejerskov, O., Larsen, M.J., Richards, A., Baelum, V. (1994). Dental tissue effects of fluoride. Adv Dent Res., 8:15-31
Ghazawi, N.A., El-Shranoubi, E.D., El-Shazly, M.M., Abdel Rahman, K.M., 2007. Effects of azadirachtin on mortality rate and reproductive system of the grasshopper Heteracris littoralis Ramb. (Orthoptera: Acrididae). J. Orthopt. Res. 16, 57-65.
Gillott, C., Gaines, S.B., 1992. Endocrine regulation of male accessory-gland development and activity. Can. Entomol. 124, 871-886.
Golden, A.L., Moline, J.M., Bar-Chama, N., 1999. Male reproduction and environmental and occupational exposures: a review of epidemiologic methods. Salud Publica Mex. 41, S93-S105.
Gorshkov, V., Blenau, W., Koeniger, G., Rompp, A., Vilcinskas, A., et al. 2015. Protein and peptide composition of male accessory glands of apis mellifera drones investigated by mass spectrometry. PLoS One 10, e0125068. https://doi.org/10.1371/journal.pone.0125068
Guillette, L.J. Jr., Iguchi, T., 2003. Contaminant-induced endocrine and reproductive alterations in reptiles. Pure Appl Chem. 75, 2275–2286.
Gupta, R.S., Khan, T.I., Agrawal, D., Kachhawa, J.B., 2007. The toxic effects of sodium fluoride on the reproductive system of male rats. Toxicol. Ind. Health. 23, 507-13.
Hong, L, Levy, S.M., Broffitt, B, Warren, J.J., Kanellis, M.J., Wefel, J.S., Dawson, D.V. (2006). Timing of fluoride intake in relation to development of fluorosis on maxillary central incisors. Community. Dent. Oral. Epidemiol., 34: 299-309
Jha, S.K., Mishra, V.K., Sharma, D.K. (2011). Damodaran T. Fluoride in the environment and its metabolism in humans. In: anonymous reviews of environmental contamination and toxicology. New York: Springer; P. 121-142.
Jia-Xi, W., Bian, Y.M. (1988). Fluoride effects on the mulberry-silkworm system, Environ. Pollut. 52: 11–18.
Jobling, S., Williams, R., Johnson, A., Taylor, A., Gross-Sorokin, M., Nolan, M., Tyler C.R., Aerle, R.V., Santos, S., Brighty, G., 2006. Predicted exposures to steroid estrogens in UK rivers correlate with widespread sexual disruption in wild fish populations. Environ Health Perspect 114, 32–39.
Kanippayoor, R.L., Alpern J.H.M., Moehring. A.J., 2013. Protamines and spermatogenesis in Drosophila and Homo sapiens A comparative analysis. Spermatogenesis. 3, 1-7.
Kerns, D.L., Gaylor, M.J., 1992. Sublethal effects of insecticides on cotton aphid reproduction and color morph development. Southwest Entomol. 17, 245-250.
Kim, I., Xu, W., Reed, J.C. (2009). Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat. Rev. Drug Discov. 7: 1013–1030.
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. doi: 10.4103/0974-1208.74159
Long, H., Jin, Y., Lin, M., Sun, Y., Zhang, L., Clinch, C., 2009. Fluoride toxicity in the male reproductive system. Fluoride. 42, 260-276.
Ma, W.G., Song, H., Das, S.K., Paria, B.C., Dey, S.K., 2003. Estrogen is a critical determinantthat specifies the duration of the window ofuterine receptivity for implantation. Proc Natl AcadSci USA. 100, 2963-2968.
Mailloux, R.J., Harper, M.E. (2011). Uncoupling proteins and the control of mitochondrial reactive oxygen species production. Free Radic. Biol. Med. 51: 1106–1115
Martin, R.H., 2008. Meiotic errors in human oogenesis and spermatogenesis. Reprod. Biomed. 16, 523-531.
Martínez-Mier, E.A. (2012). Fluoride: its metabolism, toxicity, and role in dental health. J. Evid. Based. Complement. Alternat. Med. 17: 28-32
Mathur, N., Pandey G., Jain, G.C., 2010. Pesticides: a review of the male reproductive toxicity. Journal of Herbal Medicine and Toxicology. 4, 1-8.
McCoy, K.A., Bortnick, L.J., Campbell, C.M., Hamlin, H.J., Guillette, L. J., St. Mary, C.M., 2008. Agriculture Alters Gonadal Form and Function in the Toad Bufomarinus. Environ Health Perspect 116, 1526-1532.
Moline, J.M., Golden, A.L., Bar-Chama, N., Smith, E., Rauch, M.E., Chapin, R.E., Perreault, S.D., Schrader, S.M., Suk, W.A., Landrigan, P.J., 2000. Exposure to hazardous substances and male reproductive health: a research framework. Environ Health Perspect. 108, 803–813.
Oliva, R., 2006. Protamines and male infertility. Hum. Reprod. Update. 12, 417-35.
Ozsvath, D.L. (2009). Fluoride and environmental health: a review. Rev Environ Sci Bio Technol. 8: 59-79.
Podder, S., Akbari, S., Roy, S., 2012. Cryolite Induced Morphological Change in the compound eye of Drosophila melanogaster. Fluoride. 45, 58–64.
Ram, R.K., Wolfner, M.F., 2007. Seminal influences: Drosophila Acps and the molecular interplay between males and females during reproduction. Integr. Comp. Biol. 47, 427-445.
Ranjan, R., Ranjan, A. (2015). Fluoride toxicity in animals. New York: Springer.
Roy, P., Phukan, P.K., Changmai, D., Boruah, S., 2017. Pesticides, insecticides and male infertility, Int. J .Reprod. Contracept. Obstet. Gynecol. 6, 3387-3391.
Scharf, M.E., Suiter, D.R., 2011. [Insecticide Primer] Insecticide Mode of Action, PCT Magazine.
Schwartz, J.M., Woodruff, T.J., 2008. Shaping Our Legacy: Reproductive Health and the Environment. San Francisco: University of California-San Francisco, National Center of Excellence in Women’s Health. 39.
Shakeet, P., Bakshi, S., 2009a. Histopathological effect of cypermethrin on gonads of Chrotogonus trachypterus Blan. (Orthoptera: Acrididae). Pak. entomol. 31, 17-24.
Shakeet, P., Bakshi, S., 2009b. Histopathology of gonads of Chrotogonus trachypterus (Blanchard) with sublethal dose of monocrotophos. J. Agric. Sci. (Karnataka). 22, 507-510.
Sharma, V., Pandey, A.K., Kumar, A., Misra, S., Gupta, H.P.K., Gupta, S., et al. 2017. Functional male accessory glands and fertility in Drosophila require novel ecdysone receptor. PLOS Genetics. https://doi.org/10.1371/journal.pgen.1006788
Shulman, J.D., Wells, L.M. (1997). Acute ethanol toxicity from ingesting mouthwash in children younger than 6-years of age. Pediatr Dent. 19: 404-408.
Song, G.H., Gao, J.P., Wang, C.F., Chen, C.Y., Yan, X.Y., Guo, M., Wang, Y., Huang, F.B. (2014). Sodium fluoride induces apoptosis in the kidney of rats through caspase-mediated pathways and DNA damage. J. Physiol. Biochem. 70: 857–868.
Sonne, C., Leifsson, P.S., Dietz, R., Born, E.W., Letcher, R.J., Hyldstrup, L., Riget, F.F., Kirkegaard, M., Muir, D.C., 2006. Xenoendocrine pollutants may reduce size of sexual organs in East Greenland polar bears (Ursusmaritimus). Environ Sci Technol. 40, 5668–5674.
Srinivasa, J., Maxim, P., Urban, J., D’Souza, A., 2005. Effects of Pesticides on Male Reproductive Functions. Iran J. Med. Sci. 30, 153-159.
Swan, S.H., 2006. Semen quality in fertile US men in relation to geographical area and pesticide exposure. Int J Androl, 29, 62–68.
Tian, Y., Huo, M., Li, G., Li, Y., Wang, J. (2016). Regulation of LPS-induced mRNA expression of pro-inflammatory cytokines via alteration of NF-κB activity in mouse peritoneal macrophages exposed to fluoride. Chemosphere. 161: 89–95.
Tokuyasu, K.T., Peacock, W.J., Hardy, R.W., 1972. Dynamics of spermiogenesis in Drosophila melanogaster. I. Individualization process. Z. Zellforsch. Mikrosk. Anat. 124, 479-506. http://dx.doi.org/10.1007/BF00335253.
Whorton, D., Krauss, R.M., Marshall, S., Milby, T.H., 1977. Infertility in male pesticide workers. Lancet. 2, 1259-1261. Wyrobek, A.J., Watchmaker, G., Gordon, L., Wong, K., Moore, D., Whorton D., 1981. Sperm shape abnormalities in carbaryl-exposed employees. Environ Health Perspect. 40, 255-265.
Wyatt, G.R., 1991. Gene regulation in insetcs. Invertebr Repr Dev. 20, 1-35.
Yang, K., Liang, X. (2011). Fluoride in drinking water: effect on liver and kidney function. New York: Elsevier; P. 769-775.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an open access article under the CC BY-NC-ND license Creative Commons Attribution-Noncommercial 4.0 International (CC BY-NC 4.0).
