Fluoride and Genetic DamageFluoride affects most, if not all, of the body's processes in one way or another. How fluoride might affect reproduction have been widely studied. Most of the research has been conducted on lower forms of life, such as fruit flies. However, genetic effects are also found in mammals, including Man. Here are some examples: Susheela AK, Jethanandani P. Circulating testosterone levels in skeletal fluorosis patients. J Toxicol Clin Toxicol 1996; 34: 183-9 OBJECTIVE: The present study focuses on serum testosterone concentrations in patients with skeletal fluorosis, in order to assess the hormonal status in fluoride toxicity. METHODS: Serum testosterones were compared for patients afflicted with skeletal fluorosis (n = 30) and healthy males consuming water containing less than 1 ppm fluoride (Control 1, n = 26) and a second category of controls (Control 2, n = 16): individuals living in the same house as the patients and consuming same water as patients but not exhibiting clinical manifestations of skeletal fluorosis. RESULTS : Circulating serum testosterones in skeletal fluorosis patients were significantly lower than those of Control 1. Testosterone concentrations of Control 2 were also lower than those of Control 1 but were higher than those of the patient group. CONCLUSIONS : Decreased testosterone concentrations in skeletal fluorosis patients and in males drinking the same water as the patients but with no clinical manifestations of the disease compared with those of normal, healthy males living in areas nonendemic for fluorosis suggest that fluoride toxicity may cause adverse effects in the reproductive system of males living in fluorosis endemic areas. Chinoy NJ , Narayana MV. In vitro fluoride toxicity in human spermatozoa. Fluoride 1994; 27: 231-232. Effects of sodium fluoride (NaF) on washed, ejaculated human spermatozoa at doses of 25, 50, and 250 mM were investigated in vitro at intervals of 5, 10, and 20 min. Sodium fluoride (NaF) did not affect the extracellular pH of sperm, except that a slight acidification was caused by the 250 mM dose only. The treatment caused a significant enhancement in acid phosphatase and hyaluronidase activities after 5 and 10 min. However, the decrease in the lysosomal enzyme activity after 20 min treatment could have been due to the gradual increase in fluoride accumulation by spermatozoa leading to membrane damage. Silver nitrate staining of sperm revealed elongated heads, deflagellation. and loss of the acrosome together with coiling of the tail. Sperm glutathione levels also showed a time-dependent decrease with complete depletion after 20 min, indicating rapid glutathione oxidation in detoxification of the NaF. The altered lysosomal enzyme activity and glutathione levels together with morphologic anomalies resulted in a significant decline in sperm motility with an effective dose of 250 mM. Freni SC , Exposure to high fluoride concentrations in drinking water is associated with decreased birth rates. Journal of Toxicology and Environmental Health 1994; 42: 109-12. A review of fluoride toxicity showed decreased fertility in most animal species studied. The current study was to see whether fluoride could also affect human birth rates. A U.S. database of drinking water systems was used to identify index counties with water systems reporting fluoride levels of at least 3 ppm. These and adjacent counties were grouped in 30 regions spread over 9 states. For each county, two conceptionally different exposure measures were defined, and the annual total fertility rate (TFR) for women in the age range 10-49 yr was calculated for the period 1970-1988. For each region separately, the annual TFR was regressed on the fluoride measure and sociodemographic covariables. Most regions showed an association of decreasing TFR with increasing fluoride levels. Meta-analysis of the region-specific results confirmed that the combined result was a negative TFR/fluoride association with a consensus combined p value of .0002-.0004, depending an the analytical scenario. There is no evidence that this outcome resulted from selection bias, inaccurate data, or improper analytical methods. However, the study is one that used population means rather than data on individual women. Whether or not the fluoride effect on the fertility rate found at the county level also applies to individual women remains to be investigated. Narayana MV, Chinoy NJ. Effect of fluoride on rat testicular steroidogenesis. Fluoride 1994; 27: (Research Report 7), 17-12. In view of reports of infertility among human populations in fluorosis prevailing regions, we investigated the effect of fluoride ingestion on testicular steroidogenesis in rats. Sodium fluoride (NaF) was administered to the rats orally at a daily dose of 10mg/kg bodyweight for 50 days. The treatment did not cause significant change in testicular cholesterol levels, indicating that metabolism was not altered and that there was no hypo/hypercholesterolemic effect. In addition, activities of the intermediary enzymes in androgenesis, viz., 3ß- and 17ß-hydroxysteroid dehydrogenase were only modestly decreased by NaF ingestion. Subsequently, the determination of circulating androgen levels was similar in NaF-treated rats showed a downward trend compared to those ofthe control group, suggesting alteration in testosterone concentration. The histomorphometric studies revealed significant change in the Leydig cell diameter m correlation with the androgen levels. These results indicate that fluoride does interfere with steroidogenesis in short-term lowdose exposures in rats. Susheela AK, Kumar A. A study of the effect of high concentrations of fluoride on the reproductive organs of male rabbits, using light and scanning electron microscopy. J. of Reproduction and Fertility 1991; 92: 353-360. Fluoride was orally administered to rabbits at 10 mg NaF/kg body weight for 18 or 29 months. The animals were then killed and and the structure of the testis, epididymis and vas deferens studied under light and scanning electron microscopes. In animals treated for 29 months, the spermatogenic cells in the seminiferous tubules were disrupted, degenerated and devoid of sperrnatozoa. In animals treated for 18 or 29 months, loss of cilia on the epithelial cells lining the lumen of the ductus efferentes of the caput epididymidis and of stereocilia on the epithelial cells lining the lumen of the vas deferens was observed. In some regions of the epithelial lining of the lumen of the ductuli efferentes and vas deferens, the boundaries of the cells were not clear and appeared to be peeled off. Mucus droplets were abundant in the vas deferens of control animals, but absent in both the treated groups. Spermatogenesis ceased only in the animals treated for 29 months. The difference in the structural changes observed in the testes of the two treated groups may have been due to the blood-testis barrier. It is concluded that ingestion of high concentrations of fluoride has harmful effects on the male reproductive system.
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