Fluoride Exposure, Follicle Stimulating Hormone Receptor Gene Polymorphism and Hypothalamus-pituitary-ovarian Axis Hormones in Chinese Women.

The effects of fluoride exposure on the functions of reproductive and endocrine systems have attracted widespread attention in academic circle nowadays. However, it is unclear whether the gene-environment interaction may modify the secretion and activity of hypothalamus-pituitary- ovarian (HPO) axis hormones. Thus, the aim of this study was to explore the influence of fluoride exposure and follicle stimulating hormone receptor (FSHR) gene polymorphism on reproductive hormones in Chinese women. A cross sectional study was conducted in seven villages of Henan Province, China during 2010-2011. A total of 679 women aged 18-48 years were recruited through cluster sampling and divided into three groups, i.e. endemic fluorosis group (EFG), defluoridation project group (DFPG), and control group (CG) based on the local fluoride concentration in drinking water. The serum levels of gonadotropin releasing hormone (GnRH), follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were determined respectively and the FSHR polymorphism was detected by real time PCR assay. The results provided the preliminary evidence indicating the gene-environment interaction on HPO axis hormones in women.

Effect of oxidative stress on fluoride-induced apoptosis in primary cultured Sertoli cells of rats.

This study examined the effect of oxidative stress on the apoptosis of Sertoli cells induced by sodium fluoride (NaF). Cell viability, reactive oxygen species, malondialdehyde content, superoxide dismutase activity, mitochondrial membrane potential, and apoptosis were measured after the rat Sertoli cells were exposed to various concentrations of (0, 6, 12, and 24 µg/ml) sodium fluoride in the presence and absence of 2 mM N-acetylcysteine (NAC) for 24 h. The present study showed that decrease in cell viability and excessive oxidative stress were observed in NaF-treated cells. The treatment with NAC restored the decreased cell viability and excessive oxidative stress. Moreover, fluoride exposure decreased mitochondrial membrane potential and increased apoptosis in Sertoli cells. NAC was also found to suppress a loss of mitochondrial membrane potential and the percentage of apoptosis in NaF-treated Sertoli cells. This study proved that oxidative stress probably play a major role in NaF-induced apoptosis of Sertoli cells.

[Study on the relationship between ER Rsa I gene polymorphism and children's dental fluorosis].

OBJECTIVE: To explore the distribution of ER Rsa I genotype in children who lived in the areas with or without high fluoride, and evaluate the relationship between ER Rsa I gene polymorphism and children's dental fluorosis. METHODS: Children aged 8 to 12 years, born and raised in high fluoride areas and control areas in two counties of Henan Province were recruited. The Rsa I marker of ER gene was genotyped in 237 children composed of both dental fluorosis cases and controls by PCR-RFLP procedure. Urine fluoride was detected with fluoride ion selective electrode method. RESULTS: The frequency distribution of ER Rsa I genotype was rr 60.81% (45/74), Rr 27.02% (20/74), RR 12.16% (9/74) in children with fluorosis; rr 73.91% (51/69), Rr 20.29% (14/69), RR 5.80% (4/69) in children without fluorosis from high fluoride areas, and rr 63.83% (60/94), Rr 34.04% (32/94), RR 2.13% (2/94) in the children without fluorosis from control areas respectively. There were no significant differences in the three groups (P>0.05), but children carrying allele R of ER Rsa I had a significantly increased risk of dental fluorosis (OR=1.821, 95% CI: 1.013-3.274) compared to children carrying the allele r in endemic fluorosis areas. CONCLUSION: Although no significant difference was found in ER Rsa I genotype between cases and non-dental fluorosis in endemic fluorosis areas, children carrying R allele of ER Rsa I had a higher risk compared to children carrying r allele, and the further study is needed.

Endemic fluorosis in Henan province, China: ERα gene polymorphisms and reproductive hormones among women.

BACKGROUND AND OBJECTIVES: The aim of this study was to explore the influence of fluoride exposure and ERα gene polymorphisms on reproductive hormone concentrations of women in accordance with endemic fluorosis residence. METHODS AND STUDY DESIGN: A cross sectional study was conducted in Tongxu county, Henan Province, China. A total of 679 women were recruited using cluster sampling and each subject provided fasting blood and an associated urine sample. We measured the concentrations of serum gonadotropin releasing hormone (GnRH), follicle-stimulating hormone, luteinizing hormone, and estradiol and urinary fluoride. RESULTS: In the defluoridation project group (DFPG), serum GnRH was lower in women carrying C/C genotype compared to in those carrying C/T and T/T genotypes of ERα gene rs3798577 (p<0.05). In the endemic fluorosis group (EFG), serum GnRH was lower in women carrying Pp genotype compared to in those carrying PP and pp genotypes of ERα PvuII (p<0.05). Serum GnRH in women from EFG who carried Pp, pp, Xx and xx genotypes in ERα gene PvuII and XbaI was lower than in those in the control group (CG) who carried same genotypes (p<0.05). Furthermore, serum GnRH in women from EFG was significantly lower than in those in CG, regardless of whether the women were carrying C/C, C/T or T/T genotypes of ERα rs3798577 (p<0.05). Serum estradiol concentrations in EFG were significantly lower than in CG when the women were carrying the Pp, Xx and T/T genotypes in ERα gene (p<0.05). CONCLUSION: Interaction of ERα gene and fluoride exposure may influence women's serum reproductive hormone concentrations.

[Relationship between spermatogenic cell apoptosis and serum estradiol level in rats exposed to fluoride].

OBJECTIVE: To observe the relationship between spermatogenic cell apoptosis and serum estradiol level in rats exposed to fluoride. METHODS: A total of 30 male Wistar rats were allocated into six groups randomly. The six experimental groups were 28-day control group, 28-day low-dose fluoride treatment group, 28-day high-dose fluoride treatment group, 38-day control group, 38-day low-dose fluoride treatment group, and 38-day high-dose fluoride treatment group. The fluorosis model was acquired by subcutaneous injection of NaF solution. The content of NaF in testis was measured by using fluorine selective electrode. The serum estradiol level was radioimmunochemically detected. And the apoptotic spermatogenic cells were quantitatively measured by TUNEL. RESULTS: The content of NaF in testis and the ratio of apoptotic spermatogenic cell in fluoride treatment groups significantly increased with increased experimental dosage and prolonged experimental period (P < 0.05). Meanwhile, the serum estradiol level significantly decreased (P < 0.05), which was negatively correlated with the content of NaF in testis as well as the ratio of apoptotic spermatogenic cell (P < 0.05). CONCLUSION: Excessive fluoride could lead disturbance to serum estradiol level during some range of dose and time, which is an important factor to spermatogenic cell apoptosis.

Serum calciotropic hormone levels, and dental fluorisis in children exposed to different concentrations of fluoride and iodine in drinking water.

BACKGROUND: High fluoride exposure can result in dental fluorosis. Fluoride and iodine are coexistent in the drinking water of areas in China and may affect the prevalence of dental fluorosis and osteogenesis. The aim of this study was to investigate the relationship between serum calciotropic hormone level, and dental fluorisis in children exposed to different concentrations of fluoride and iodine in drinking water. METHODS: A pilot study was conducted in three villages located in the Kaifeng and Tongxu counties of Henan Province, China in 2006. Children aged 8 to 12 years, born and raised in the three villages were recruited. The fluoride levels in the samples of urine from these children were detected by fluoride ion selective electrode. Calcitonin and osteocalcin levels in the serum, and serum calcium were measured by radioimmunassay and flame atomic absorption spectrometry, respectively. RESULTS: Fluoride levels in urine were significantly lower in children from control area (CA) as compared with those from the high fluoride & iodine areas (HFIA) and the high fluoride area (HFA) (P < 0.05 respectively), and no statistically significant difference was found between the children from HFIA and HFA. Additionally, calcitonin levels in the serum were significantly lower in children from CA and HFA as compared with that from HFIA (P < 0.05 respectively), and osteocalcin levels in the serum was lower in children from CA than those from HFIA (P < 0.05). No statistically significant difference in serum osteocalcin concentrations was found between children from HFA and HFIA. CONCLUSION: This study provides an evidence that iodine exposure may modify the serum calciotropic hormone levels related to fluorine exposure.