Testicular - Adverse Effects
Sodium fluoride
CAS No. 7681-49-4
 
 

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• Note: The following is a limited selection of abstracts from 1994 to present.
• Due to length, we present this as a separate section
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May 3, 2004. Submission to: National Research Council Committee: Toxicologic Risk of Fluoride in Drinking Water. From Ellen Connett. Title of Submission: Fluoride's adverse effects on the Male Reproductive system

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12220599&dopt=Abstract

Reprod Toxicol 2002. Jul;16(4):385

Testicular toxicity in sodium fluoride treated rats: association with oxidative stress.

Ghosh D, Das(Sarkar) S, Maiti R, Jana D, Das U.

Department of Human Physiology with Community Health, Reproductive Endocrinology and Family Welfare Research Unit, Vidyasagar University, 721 102, West Bengal, Midnapore, India

This study examined the effect of sodium fluoride, a water pollutant important through the world, including India, on testicular steroidogenic and gametogenic activities in relation to testicular oxidative stress in rats. Sodium fluoride treatment at 20mg/kg/day for 29 days by oral gavage resulted in significant diminution in the relative wet weight of the testis, prostate, and seminal vesicle without alteration in the body weight gain. Testicular Delta(5),3beta-hydroxysteroid dehydrogenase (HSD) and 17beta-HSD activities were decreased significantly along with significant diminution in plasma levels of testosterone in the fluoride-exposed group compared to the control. Epididymal sperm count was decreased significantly in the fluoride-treated group and qualitative examination of testicular sections revealed fewer mature luminal spermatozoa in comparison to the control. The seminiferous tubules were dilated in treated animals. Fluoride treatment was associated with oxidative stress as indicated by an increased level of conjugated dienes in the testis, epididymis, and epididymal sperm pellet with respect to control. Peroxidase and catalase activities in the sperm pellet were decreased significantly in comparison to the control. The results of this experiment indicate that fluoride at a dose encountered in drinking water in contaminated areas exerts an adverse effect on the male reproductive system and this effect is associated with indicators of oxidative stress.


PMID: 12220599 [PubMed - as supplied by publisher]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12865044&dopt=Abstract

Environ Res 2003. Sep;93(1):20-30.

Fluoride-induced disruption of reproductive hormones in men.


Ortiz-Perez D, Rodri;guez-Marti;nez M, Marti;nez F, Borja-Aburto VH, Castelo J, Grimaldo JI, de la Cruz E, Carrizales L, Diaz-Barriga F.

Laboratorio de Toxicologi;a Ambiental, Facultad de Medicina, Universidad Autonoma de San Luis Potosi;, Av. Venustiano Carranza 2405, Col. Lomas Filtros, CP 78210, San Luis Potosi;, Mexico

Fluoride-induced reproductive effects have been reported in experimental models and in humans. However, these effects were found in heavily exposed scenarios. Therefore, in this work our objective was to study reproductive parameters in a population exposed to fluoride at doses of 3-27mg/day (high-fluoride-exposed group-HFEG). Urinary fluoride levels, semen parameters, and reproductive hormones in serum (LH, FSH, estradiol, prolactin, inhibin-B, free and total testosterone) were measured. Results were compared with a group of individuals exposed to fluoride at lower doses: 2-13mg/day (low-fluoride-exposed group-LFEG). A significant increase in FSH (P<0.05) and a reduction of inhibin-B, free testosterone, and prolactin in serum (P<0.05) were noticed in the HFEG. When HFEG was compared to LFEG, a decreased sensitivity was found in the FSH response to inhibin-B (P<0.05). A significant negative partial correlation was observed between urinary fluoride and serum levels of inhibin-B (r=-0.333, P=0.028) in LFEG. Furthermore, a significant partial correlation was observed between a chronic exposure index for fluoride and the serum concentrations of inhibin-B (r=-0.163, P=0.037) in HFEG. No abnormalities were found in the semen parameters studied in the present work, neither in the HFEG, nor in the LFEG. The results obtained indicate that a fluoride exposure of 3-27mg/day induces a subclinical reproductive effect that can be explained by a fluoride-induced toxic effect in both Sertoli cells and gonadotrophs.

PMID: 12865044 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14502225&dopt=Abstract

EMBO Rep. 2003 Sep 19 [Epub ahead of print].

Spatiotemporal dynamics of the COPI vesicle machinery.

Elsner M, Hashimoto H, Simpson JC, Cassel D, Nilsson T, Weiss M.

Cell Biology and Cell Biophysics Programme, EMBL, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.

Assembly of the coat protein I (COPI) vesicle coat is controlled by the small GTPase ADP ribosylation factor 1 (ARF1) and its GTPase-activating protein, ARFGAP1. Here, we investigate the diffusional behaviours of coatomer, the main component of the coat, and also those of ARF1 and ARFGAP1. Using fluorescence-correlation spectroscopy, we found that most ARF1 and ARFGAP1 molecules are highly mobile in the cytosol (diffusion constant D approximately 15 microm(2) s(-1)), whereas coatomer diffuses 5-10 times more slowly than expected (D approximately 1 microm(2) s(-1)). This slow diffusion causes diffusion-limited binding kinetics to Golgi membranes, which, in FRAP (fluorescence recovery after photobleaching) experiments, translates into a twofold slower binding rate. The addition of aluminium fluoride locks coatomer onto Golgi membranes and also decreases the binding kinetics of both ARF1 and ARFGAP1, suggesting that these proteins function in concert to mediate sorting and vesicle formation.

PMID: 14502225 [PubMed - as supplied by publisher]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12220599&dopt=Abstract

Reprod Toxicol 2002 Jul;16(4):385

Testicular toxicity in sodium fluoride treated rats: association with oxidative stress.

Ghosh D, Das(Sarkar) S, Maiti R, Jana D, Das U.

Department of Human Physiology with Community Health, Reproductive Endocrinology and Family Welfare Research Unit, Vidyasagar University, 721 102, West Bengal, Midnapore, India

This study examined the effect of sodium fluoride, a water pollutant important through the world, including India, on testicular steroidogenic and gametogenic activities in relation to testicular oxidative stress in rats. Sodium fluoride treatment at 20mg/kg/day for 29 days by oral gavage resulted in significant diminution in the relative wet weight of the testis, prostate, and seminal vesicle without alteration in the body weight gain. Testicular Delta(5),3beta-hydroxysteroid dehydrogenase (HSD) and 17beta-HSD activities were decreased significantly along with significant diminution in plasma levels of testosterone in the fluoride-exposed group compared to the control. Epididymal sperm count was decreased significantly in the fluoride-treated group and qualitative examination of testicular sections revealed fewer mature luminal spermatozoa in comparison to the control. The seminiferous tubules were dilated in treated animals. Fluoride treatment was associated with oxidative stress as indicated by an increased level of conjugated dienes in the testis, epididymis, and epididymal sperm pellet with respect to control. Peroxidase and catalase activities in the sperm pellet were decreased significantly in comparison to the control. The results of this experiment indicate that fluoride at a dose encountered in drinking water in contaminated areas exerts an adverse effect on the male reproductive system and this effect is associated with indicators of oxidative stress.


PMID: 12220599 [PubMed - as supplied by publisher]


Fluoride 2002; 35(3):153-160

In vitro influence of sodium fluoride on ram semen quality and enzyme activities

Zakrzewska H (a), Udala J (b), Blaszczyk B (b)

(a) For correspondence: Dr. H. Zakrzewska, Dept. of Biochemistry, Agricultural University, 17 Slowackiego Street, 71-434 Szczecin, Poland

Summary: The percentage of spermatozoa in ram semen with intact acrosomes and the level of spermatozoa motility decreased significantly after dilution and after 5 hr incubation at 38¼C. Both indices decreased significantly in the presence of NaF at concentrations ranging from 20 ugmol/L to 0.1 mol/L. 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 ugmol/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). The activity of asparate transaminase (AspAT) displayed a large increase with the increasing lower F- concentration. These changes undoubtedly affect the physiological functions of the sperm.


From TOXNET

Chung-Kuo Kung Kung Wei Sheng (China Public Health) 2000 Aug;16(8):697-8

[The primary study of antagonism of selenium on fluoride-induced reproductive toxicity of male rat]

[Article in Chinese]

Zhu XZ, Ying CJ, Liu SH, Yang KD, Wang QZ.

Department of Clinic Nutrition, Tongji Hospital Tongji Medical University, Wuhan, China.

English Abstract Indicator: A Abstract: The protective effect of ascorbic acid at dose level of 1.0 mg/L in drinking water against the fluoride-induced damage on reproductive system of rat was studied. 150 mg/L sodium fluoride (NaF) in drinking water of male rat can cause the significant decrease of sperm count and mobility, the increase of serum and testicular lipid peroxides (LPO) contents, and the adenosine triphosphatase (ATPase) activity depression of epididymis. All of those effects are reversible by adding adequate ascorbic acid in drinking water simultaneously. The effects of ascorbic acid against fluoride-induced damages are similar to those produced by 2.0 mg/L Na2SeO3 in the drinking water of rats. However, no significant recovery of fluoride-induced effects on GSH-Px activities in the tissues of testis and epididymis were observed in ascorbic acid and fluoride group. The mechanism of ascorbic acid on fluoride-induced damage of male reproductive system need to be further studied.


Dart Special at Toxnet

Environmental Sciences: an International Journal of Environmental Physiology and Toxicology. 2000;7(1):29-38

Reversal of fluoride-induced alteration in cauda epididymal spermatozoa and fertility impairment in male mice.

Chinoy NJ and Sharma A

Abstract: The effects of sodium fluoride (NaF) ingestion (10 mg NaF/kg body weight) and the possible therapeutic effects of ascorbic acid (AA, 15 mg/animal/day) and/or calcium phosphate (Ca, 25 mg/animal/day) on the reproductive functions and fertility of male mice were investigated. NaF-ingestion brought about a significant decline in sperm acrosomal acrosin and hyaluronidase. Cauda epididymal sperm stained with alcoholic acidic silver nitrate reagent revealed acrosomal damage and deflagellation. However, sperm nuclear integrity was not affected by the treatment. The reduced activity of the enzymes as well as the structural and metabolic alterations in the sperm led to a significant decrease in sperm count, and motility and live:dead ratios but an increase in abnormal sperm which ultimately lead to a poor fertility rate. The cessation of NaF-treatment was not conducive to bringing about a complete recovery. However, the administration of AA or Ca to NaF-treated mice revealed significant recovery from fluoride toxicity in all the above parameters. The recovery was more pronounced in the animal group treated with both AA and calcium in combination, thus indicating a synergistic or additive action. It is concluded that fluoride has a definite effect on male reproduction and fertility. However, the effects are transient and reversible with the administration of AA and Ca. Therefore, AA and Ca are proposed as therapeutic agents for populations in endemic areas for the amelioration of fluoride effects on reproductive functions.


Full report available at http://www.fluoride-journal.com/98-31-4/314-203.htm

Fluoride 1998; 31(4):203-216

Amelioration of fluoride toxicity by Vitamins E and D in reproductive functions of male mice

NJ Chinoy * and A Sharma

*Address for correspondence. Reproductive Endocrinology and Toxicology Unit, UGC Department of Special Assistance and COSIST in Zoology, School of Sciences, Gujarat University, Ahmedabad 380009, India.

SUMMARY: Studies on the beneficial effects of vitamins E and D supplementation on functions of caput and cauda epididymides, their spermatozoa, vas deferens and seminal vesicle of sodium fluoride (NaF) treated (10 mg/kg body weight) male mice (Mus musculus) were carried out. The NaF treatment resulted in significant decrease in the body and epididymis weight but those of vas deferens and seminal vesicle were not affected. NaF treatment brought about alterations in epididymal milieu as elucidated by the significant decrease in levels of sialic acid and protein as well as activity of ATPase in epididymides. As a result, the sperm maturation process was affected leading to a significant decline in cauda epididymal sperm motility and viability. This caused a significant reduction in fertility rate. The cauda epididymal sperm count was also significantly reduced. The data obtained suggest that fluoride treatment induced significant metabolic alterations in the epididymides, vas deferens and seminal vesicles of mice. The withdrawal of NaF treatment (30 days) produced incomplete recovery. On the other hand, sup-plementation of vitamins E or D during the withdrawal period of NaF treated mice was found to be very beneficial in recovery of all NaF induced effects, thus elucidating their ameliorative role in recovery from toxic effects of NaF on the reproductive functions and fertility. On the whole, a combination of vitamins E and D treatment was comparatively more effective than that with vitamin E or D alone. Therefore, vitamin therapy could be beneficial for the amelioration of fluoride induced changes in reproductive functions.


1997. A dissertation submitted to the School of Biological Sciences, University of Surrey, in fulfilment of the requirements for the Degree of Doctor of Philosophy. Guildford 1997.
The effect of fluoride on the physiology of the pinal gland
Jennifer Anne Luke

Abstract:
The purpose was to discover whether fluoride (F) accumulates in the pineal gland and thereby affects pineal physiology during early development. The [F] of 11 aged human pineals and corresponding muscle were determined using the F-electrode following HMDS/acid diffusion. The mean [F] of pineal was significantly higher (p<0.001) than muscle: 296 ± 257 vs. 0.5 ± 0.4 mg/kg respectively. Secondly, a controlled longitudinal experimental study was carried out to discover whether F affects the biosynthesis of melatonin, (MT), during pubertal development using the excretion rate of urinary 6-sulphatoxymelatonin, (aMT6s), as the index of pineal MT synthesis. Urine was collected at 3-hourly intervals over 48 hours from two groups of gerbils (Meriones unguiculatus), low-F (LF) and high-F (HF) (12 f, 12 m/group): under LD: 12 12, from prepubescence to reproductive maturity (at 9-12 weeks) to adulthood, i.e., at 7, 9, 11 1/2 and 16 weeks. The HF pups received 2.3 ug F/g BW/day from birth until 24 days whereafter HF and LF groups received food containing 37 and 7 mg F/kg respectively and distilled water. Urinary aMT6s levels were measured by radioimmunoassay. The HF group excreted significantly less aMT6s than the F group until the age of sexual maturation. At 11 1/2 weeks, the circadian profile of aMT6s by the HF males was significantly dimished but, by 16 weeks, was equivalent to the LF males. In conclusion, F inhibits pineal MT synthesis in gerbils up until the time of sexual maturation. Finally, F was associated with a significant acceleration of pubertal development in female gerbils using body weights, age of vaginal opening and accelerated development of the ventral gland. At 16 weeks, the mean testes weight of HF males was significantly less (p<0.002) than that of the LF males. The results suggest that F is associated with low circulating levels of MT and this leads to an accelerated sexual maturation in female gerbils. The results strengthen the hypothesis that the pineal has a role in pubertal development.


Fluoride 1997; 30(1):41-50

Fluoride toxicity on rat testis and cauda epididymal tissue components and its reversal

Chinoy NJ, Shukla S, Walimbe AS, Bhattacharya S

Dr. Chinoy, Professor and Head, Zoology Department, School of Sciences, Gujarat University, Ahmedabad, India.

Summary: The toxic effects were evaluated of sodium fluoride (NaF) ingestion on the physiology of tissue components of testis and epididymis of adult, male albino rats, and the possible reversal of the effects by use of some antidotes. The results revealed that the testis and cauda epididymal proteins were altered, with disappearance of some proteins and induction of some new ones. This remained unaltered during NaF ingestion, but a significant decrease occurred in phosphatidlyethanolamine, phosphatidylserine and phosphatidylinositol. Significantly low levels of glutathione after 30 days of treatment were also obtained. On comparing the alterations in protein profile, phospholipds an glutathione in both tissues, it was evident that the protein profile was disturbed more in testis than in cauda epididymis, whereas phospholipids and gluthathione levels were affected more in cauda than in testis. The investigations into reversibility showed that ascorbic acid (vitamin C) and calcium could ameliorate fluoride toxicity.


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8618252&dopt=Abstract

J Toxicol Clin Toxicol 1996;34(2):183-9

Circulating testosterone levels in skeletal fluorosis patients.

Susheela AK, Jethanandani P.

Fluor
ide and Fluorosis Research Laboratories, All India Institute of Medical Sciences, New Delhi, India.

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 at p < 0.01. Testosterone concentrations of Control 2 were also lower than those of Control 1 at p < 0.05 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.


PMID: 8618252 [PubMed - indexed for MEDLINE]


Fluoride 1995; 28(2):75-86

Amelioration of fluoride toxicity in some accessory reproductive glands and spermatozoa of rat

Chinoy NF, Narayana MV, Dalal V, Rawat M, Patel D

Reproductive Endocrinology and Toxicology Unit, School of Sciences, Gujarat University, Ahmedabad 380 009, India

Summary: Sodium fluoride (NaF) at a dose of 10 mg/kg body weight was administered orally to male rats (Rettus norvegicus) daily for 30 and 50 days to evaluate the effect of the physiology of some sex accessory glands and sperm functions. The effects of withdrawal upon cessation of NaF ingestion, and of administering ascorbic acid (AA) and/or calcium (Ca++) along with NaF, were also investigated. The results revealed that the NaF treatment caused a significant elevation in serum fluoride levels with a simultaneous rise in Ca++ levels. This could be attributed to the formation of a calcium fluoride complex leading to calcium accumulation. The treatment resulted in structural and metabolic alterations in sperm, leading to low sperm motility, a low sperm mitochondrial activity index (SMAI), reduced viability (live:dead ratio), and changes in sperm membrane phospholipids (particularly phosphatidylinositol, phosphatidylserine and phosphatidylethanolamine, which would affect hormone receptor interaction and their functions). A significant reduction in electrolyte levels of sperm also occurred which would also affect their viability. The protein levels in cauda epididymal sperm suspension, vas deferens, seminal vesicle and prostate were significantly decreased after NaF administration, which may be due to altered protein metabolism by interference of fluoride ions. The changes in epididymal protein profile, with absence of some proteins and induction of some new ones, were probably a result o the "stress proteins" in NaF-treated rats affecting the structural and functional integrity of sperm. Glycogen accumulation in vas deferens and a decrease in fructose in seminal vesicles and vas deferens indicated disturbances in carbohydrate metabolism in these organs. However, withdrawl of treatment resulted in partial recovery. A significant recovery from NaF-induced toxic effects occurred following administation of ascorbic acid and/or calcium, while combined treatment (AA + Ca++) for 70 days manifested a synergistic effect. The transient fluoride-induced effects were reversible.

The results, corroborated by earlier data from our laboratory, show that fluoride has a definite effect on male reproduction and fertility. Ascorbic acid and calcium are proposed as therapeutic agents in endemic populations for ameiloration of effects of fluoride.


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7734335&dopt=Abstract

Int J Exp Pathol 1995 Feb;76(1):1-11

Effects of chronic fluoride toxicity on the morphology of ductus epididymis and the maturation of spermatozoa of rabbit.

Kumar A, Susheela AK.

Department of Anatomy, All India Institute of Medical Sciences, New Delhi.

This study used light and scanning electron microscopy to observe the effect of chronic fluoride toxicity on the structure of the ductus epididymis, testis and spermatozoa in rabbit. The rabbits were treated with 10 mg NaF/kg body weight/day for 20 and 23 months. Serum fluoride was estimated by the fluoride ion-specific electrode method. Fluoride levels in the sera of both 20 and 23-month treated rabbits were significantly increased (P < 0.001). Loss of stereocilia, significant decrease (P < 0.001) in the height of the pseudostratified columnar epithelium and significant increase (P < 0.001) in the diameter of both the caput and cauda ductus epididymis were observed only in the 23-month fluoride treated rabbits. The decreases in the epithelial cell height (P < 0.01) and the tubular diameter (P < 0.001) of the testis were significant only in 23-month treated animals. Spermatozoa in the lumen of the testis of both treated groups of animals and in the caput and cauda ductus epididymis of 20-month treated animals appeared normal, but spermatozoa in the caput and cauda ductus epididymis of 23-month treated animals were fragmented. In the 23-month fluoride treated rabbits, the weights of the caput and cauda epididymis were significantly reduced (P < 0.025) and there was also a reduction in the number of secretory granules in these organs. The structural changes observed in the caput and cauda ductus epididymis might adversely affect the maturation of spermatozoa.


PMID: 7734335 [PubMed - indexed for MEDLINE]


Fluoride 1995; 28(3):128-130

The influence of fluoride on the content of testosterone and cholesterol in rat

Zhao ZL, Wu NP, Gao WH

Department of Preventive Medicine, Ningxia Medical College, 750004 China

Summary: Fifty four Wistar male rats were randomly divided into three groups, drinking water containing 0.6 mg/L (control group). 100 mg/L, and 200 mg/L sodium fluoride, respectively. Rats were killed at the second, fourth and sixth weeks after experiment initiation, respectively. The levels of serum testosterone, testis cholesterol, and hepatic tissue cholesterol were determined. Results showed that the serum testosterone level had decreased with time in rats drinking water containing 100 and 200 mg/L fluoride. While testis cholesterol level did not change, it was significantly decreased in the liver at the fourth and sixth week when compared with the control group. Results suggest that fluoride may have some harmful effects on the reproductive system in male rats.


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8032126&dopt=Abstract

Reprod Toxicol 1994 Mar-Apr;8(2):155-9

In vitro fluoride toxicity in human spermatozoa.

Chinoy NJ, Narayana MV.

Department of Zoology, School of Sciences, Gujarat University, Ahmedabad, India.

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 (ACPase) 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.


PMID: 8032126 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7889087&dopt=Abstract

Int J Fertil Menopausal Stud 1994 Nov-Dec;39(6):337-46

Reversible effects of sodium fluoride ingestion on spermatozoa of the rat.

Narayana MV, Chinoy NJ.

Reproductive Endocrinology & Toxicology Unit, School of Sciences, Gujarat University, Ahmedabad, India.

The effects of ingestion of sodium fluoride (NaF), 10 mg/kg body weight for 50 days, on the structure and metabolism of sperm of albino rats (Rattus norvegicus), were investigated. In different groups of rats, the reversible effects upon withdrawal of NaF treatment and by administering some therapeutic agents, viz., ascorbic acid and calcium alone and in combination with NaF (50 and 70 days), on sperm structure and metabolism were also studied. The results revealed that the sperm acrosomal hyaluronidase and acrosin were reduced after 50 days of NaF treatment. Sperm stained with acidic alcoholic silver nitrate revealed acrosomal damage and deflagellation, which might be causative factors for the reduced activity of the enzymes. These alterations also resulted in a decline in sperm motility. The cauda epididymal sperm count was decreased, perhaps because of spermatogenic arrest. Thus, the low sperm motility and count ultimately contributed toward reduction in fertility by NaF treatment. However, withdrawal of NaF treatment for 70 days produced incomplete recovery, while administration of ascorbic acid and calcium, individually and in combination, brought about significant recovery of fluoride-induced effects. Thus, the effects of fluoride on sperm structure and metabolism of rats are transient and reversible.


PMID: 7889087 [PubMed - indexed for MEDLINE]


Fluoride 1994; 27(1):7-12

Effect of fluoride on rat testicular steroidogenesis

MV Narayana and NJ Chinoy

Zoology Department, School of Sciences, Gujarat University, Ahmedabad 380 009, Gujarat, India

Summary: 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 10 mg/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 adrongenesis, viz, 3B- and 17B-hydroxysteriod 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 of the control group, suggesting alteration in testosterone concentratio. The histomorphometric studies revealed significant change in the Leydig cell diameter in correlation with the androgen levels. These results indicate that fluoride does interfere with steroidogenesis in short-term low-dose exposures in rats.


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7920753&dopt=Abstract

Int J Fertil Menopausal Stud 1994 May-Jun;39(3):164-71

Ultrastructural studies of spermiogenesis in rabbit exposed to chronic fluoride toxicity.

Kumar A, Susheela AK.

Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.

OBJECTIVE--To address the role of fluoride in causing defects to spermatids and epididymal spermatozoa.
METHODS--Male rabbits were treated with 10 mg NaF/kg body weight daily for 18 months and maintained under identical laboratory conditions along with the control rabbits not given NaF. Testis and epididymis (caput) were investigated for ultrastructural details of spermatids and spermatozoa.
RESULTS--A wide variety of structural defects were observed in the flagellum, the acrosome, and the nucleus of the spermatids and epididymal spermatozoa of fluoride-treated rabbits. Abnormalities included absence of outer microtubules, complete absence of axonemes, structural and numeric aberrations of outer dense fibers, breakdown of the fibrous sheath, and structural defects in the mitochondria of the middle piece of the flagellum. Detachment and peeling off of the acrosome from the flat surfaces of the nucleus were also observed.
CONCLUSION--The abnormalities observed render the sperm nonfunctional and ineffective, and thus there is a possible role of fluoride in causing infertility.


PMID: 7920753 [PubMed - indexed for MEDLINE]


Fluoride 1994; 27(2):67-75

Beneficial effects of ascorbic acid and calcium on reproductive functions of sodium fluoride-treated prepubertal male rats

Chinoy NJ, Reddy VVPC, Michael M

Department of Zoology, School of Sciences, Gujarat University, Ahmedabad 388 009, India

Summary: The therapeutic effects of ascorbic acid and calcium (Ca2+) supplementation on reproductive functions of fluoride-treated (10 mg/kg body weight) male rats were investigated. Sodium fluoride treatement resulted in a decrease in almost all parameters studied except concentration of testicular cholesterol, which implies that androgen synthesis might not be affected by NaF treatment. Succinate dehydrogenase activity decreased in testis suggesting that its oxidative metabolism was altered by NaF treatment. Adenosine triposphatase activity, protein, and sialic acid levels in caput and cauda epididymides also showed a decrease. All these changes resulted in a significant decrease in sperm motility and thereby fertility rate. Glycogen concentrations in vas deferens were altered, probably due to impaired metabolic turnover. The fructose levels in vas deferens and seminal vesicle as well as the acid phosphatase activity in ventral prostate were also decreased significantly by NaF treatment.

On the other hand, simultaneous treatment of NaF along with ascorbic acid or calcium resulted in recovery in all the affected parameters studied. The recovery was more significant after treatment with ascorbic acid than with calcium. Therefore, ascorbic acid and calcium may be useful for amelioration of fluoride toxicity in endemic areas.

 
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