Fluoride Action Network

Fluoride’s Effect on the Male Reproductive System — In Vitro Studies

F.A.N. | April 2012 | By Michael Connett

Studies on animals have consistently found, with a few exceptions, that high exposures to fluoride can seriously damage the male reproductive system, as measured by increased oxidative stress, altered sperm morphology, reduced testosterone, reduced sperm quality, reduced sperm motility, and reduced fertility.  Studies of highly-exposed human populations have found similar associations with reduced testosterone and fertility. Consistent with these findings, 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. (Haesungcharern 1978; Kanwar 1983; Chubb 1985a,b).

  • In 1978, Haesungcharern reported that enzyme activity in ejaculated human spermatozoa is inhibited by brief exposure to 19 parts per million (1 mM) of fluoride.
  • In 1983, Kanwar reported that infusion of testes for four hours with 10 ppm of fluoride inhibited testosterone production.
  • In 1985, Chubb reported that infusion of testes for three hours with just 3 ppm fluoride inhibited testosterone production, which “emphasizes the sensitivity of steroidogenesis to fluoride.”
  • In 1994, Chinoy reported that infusion of testes for twenty minutes with 4750 ppm fluoride (but not 475 or 950 ppm) seriously damaged sperm morphology.

The most notable findings to date, however, were published in 2002 and 2006 by a team of Polish researchers. The researchers reported that exposing ram semen to just 0.38 parts per million (20 umol/L) of fluoride for five hours was sufficient to “cause a statistically significant decrease in the motility of spermatoza and the number of intact acrosomes.” (Zakrzewska 2002). The authors noted that these changes “undoubtedly affect the physiological function of the sperm.”

The Polish team’s findings are of particular importance when considering that from the 1960s to the 1990s, the use of high-concentration topical fluoride gels produced blood concentrations in boys and men that far exceeded 0.38 ppm. In tests on both children and adults, the use of topical fluoride gels at the dental office has been found to produce blood fluoride concentrations as high as 1.2 ppm, or four times higher than the concentration found to damage sperm. (Ekstrand 1980, 1981). The studies have also found that the blood fluoride concentration exceeds 0.38 ppm for up to six hours after treatment (longer than the length of time that the Polish researchers exposed the semen). Although most dentists now use precautionary procedures (e.g., suction devices) to reduce the blood fluoride levels following fluoride gel applications, available data shows that children will still routinely ingest enough fluoride from topical gels to reach blood fluoride concentrations exceeding 0.38 ppm.

While the impact of topical fluoride use on the reproductive system in children or adults has never been studied, it is worth noting that sperm density in North America and Europe significantly declined between the 1960s and 1990s, (Swan 2000) and infertility rates are believed to have increased.

Zakrzewska (2002) & (2006):

“The motility of spermatozoa results from formation of chemical energy and its transformation into mechanical energy. The quality of spermatozoa is determined primarily by their ability to move. Spermatozoa viability depends on two factors: generation of an adequate supply of ATP and effective use of ATP stores. Biochemical methods are useful for an objective assessment of semen quality. Among them is the measurement of ATP content. The aim of this work was to determine the effect of sodium fluoride at concentrations of 20, 100, 200, and 105 micromol/L on ATP content in ram semen. MATERIAL AND METHODS: Altogether, 19 ejaculates into an artificial vagina were collected from rams kept at the University of Agriculture and at the Glinna farm. Parameters of the semen were within limits acceptable for this animal species. The content of ATP was measured with a bioluminometric method and Lumat LB 9807 Berthohold luminometer. RESULTS: The semen was diluted in 0.9% NaCl and was found to contain 12.4 micromol ATP 10-(-9) spermatozoa. ATP content was reduced with rising concentrations of NaF: by 74.6% at 20 tmol/L; by 75.5% at 100 micromol/L; by 90.8% at 200 imol/L; and by 99.9% at 10(5) micromol/L. The correlation between ATP content and sperm motility was significant (r = 0.4990). There was no correlation between ATP content and sperm density.”
SOURCE: Zakrzewska H, Udala J. (2006). [In vitro influence of sodium fluoride on adenosine triphosphate (ATP) content in ram semen]. [Article in Polish]. Ann Acad Med Stetin. 52 Suppl 1:109-11.

“The activities of androgen-dependent enzymes—acid phosphatase (ACP), lactate dehydrogenase (LDH), and gamma-glutamyl transferase (y-GT-10S)—decreased significantly when the ejaculate was treated with NaF at concentrations of 20, 100, 200 µmol/L (0.38; 1.9; 3.8 ppm F-), but they returned to the initial value of the control at 0.1 mol/L (1900 ppm F-). . . . These changes undoubtedly affect the physiological functions of the sperm.”
SOURCE: Zakrzewska H, et al. (2002). In vitro influence of sodium fluoride on ram semen quality and enzyme activities. Fluoride 35: 153-160.

Chinoy & Narayana (1994)

“Fluoride-treated sperm [4,750 ppm for 20 minutes] exhibited a high percent of morphologic abnormalities, including a large number (10.59%) of elongated heads and 2.1% amorphous heads. The tail also revealed splitting (2.19%), coiling (11.6%) and deflagellation (22.43%). A few sperm had bent necks, and 16.75% of spermatozoa showed a diminutive acrosome. . . . These changes may have caused loss of membrane integrity and reduced metabolic activity, which ultimately resulted in deterioration of forward progression rating. The treatment caused a significant enhancement in poor to fair forward progression and failure of good and excellent forward progression, leading to a significant decline in sperm motility. . . . The depleted sperm GSH in the present investigation strongly suggests that, like several exogenous compounds, fluoride is largely dependent upon glutathione for detoxification.”
SOURCE: Chinoy NJ, Narayana MV. (1994). In vitro fluoride toxicity in human spermatozoa. Reprod Toxicol. 8(2):155-9.

Chubb (1985 a)

“Our studies indicate that 3 ppm fluoride ions significantly inhibit testosterone secretion by rat testes perfused in vitro. . . . In conclusion, Oxypherol-E.T. contains contaminants that are toxic to endocrine organs. Fluoride ion may be the primary endocrine toxicant.”
SOURCE: Chubb C. (1985a). Reversal of the endocrine toxicity of commercially produced perfluorochemical emulsion. Biology of Reproduction 33(4):854-8.

Chubb (1985 b)

Table from:
Chubb C. (1985). Reproductive toxicity of fluoride. Journal of Andrology 6: 59.

Secretion (ng/h-g testis)

2543 + 214
100 – 200 uM
(1.9 to 3.8 ppm)
2387 + 249
250 – 450 uM
(4.75 to 8.55 ppm)
520 + 100
1050 uM
(19.95 ppm)
22 + 1

“The results provide unequivocal evidence that 250 uM fluoride inhibits testosterone secretion by rat testes perfused in vitro. Previous investigators have reported that 5-10 mM fluoride [95 to 190 ppm] stimulates adenylate cyclase, inhibits metabolic reactions, and inhbits testosterone biosynthesis. The present observation of deleterious effects by 250 uM fluoride (5 ppm) emphasizes the sensitivity of steroidogenesis to fluoride.”
SOURCE: Chubb C. (1985b). Reproductive toxicity of fluoride. Journal of Andrology 6: 59.

Kanwar (1983)

“A marked fall (p < 0.01) in the testosterone production was recorded at a fluoride concentration of 100 ppm and testosterone synthesis was maximally inhibited (p < 0.01) at 200 ppm. There was a noticeable, though marginal, inhibition in testosterone synthesis even at 10 ppm fluoride concentration. From 1 ppm to 200 ppm, the degree of inhibition of testosterone synthesis seems to be dependent on fluoride concentration.”
SOURCE: Kanwar KC, Vig PS, Kalla NR (1983). In vitro inhibition of testosterone synthesis in the presence of fluoride ions. IRCS Medical Science 11: 813-814.

Haesungcharern (1978)

“[A]denylate cyclase from human spermatoza was inhibited by NaF, a finding at variance with those of other workers.”
SOURCE: Haesungcharern A, Chulavatnatol M. (1978). Inhibitors of adenylate cyclase from ejaculated human spermatozoa. J Reprod Fertil. 53(1):59-61.