Fluoride Exposure, Follicle Stimulating Hormone Receptor Gene Polymorphism and Hypothalamus-pituitary-ovarian Axis Hormones in Chinese Women / 生物医学与环境科学（英文）

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.

The influence of high fluoride exposure in drinking water on endocrine hormone in female / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the influence of water fluoride exposure on reproductive hormones in female.</p><p><b>METHODS</b>Cross-sectional study was conducted in seven villages of a county in Henan province by using simple random sampling including high fluoride area, defluoridation project area and control area on April, 2011 based on the preliminary study results of fluoride concentration in drinking water. Women who were born and growth or lived in the village at least 5 years and aged 18-48 years old were recruited using cluster sampling. They were divided into high fluoride group (HFG, 116 subjects), defluoridation project group (DFPG, 132 subjects) and control group (CG, 227 subjects) in accordance with the above areas. All subjects accepted questionnaire and physical checkup. Fasting blood and morning urine samples were collected. The concentration of fluoride in urine was determined by fluoride ion selective electrode method. The serum level of GnRH was detected using enzyme linked immunosorbent assay (ELISA). The serum level of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2) were determined by chemiluminesence immunoassay (CLIA).</p><p><b>RESULTS</b>The average age was (39.44 ± 7.34), (38.84 ± 8.03), (37.45 ± 7.70) years old in female from DFPG, HFG and CG respectively, there were no significant differences among the three groups (F = 3.02, P = 0.05). The urine fluoride levels were (1.34 ± 1.07), (2.59 ± 1.57), (0.92 ± 0.46) mg/ml in female from DFPG, HFG and CG respectively, there was a significant difference among three groups (F = 105.38, P < 0.01). No significant differences were observed of serum GnRH, LH, T, FSH and E2 among three groups in follicular phase (P > 0.05). The serum levels of E2 in Ovulatory period were 67.73, 58.09, 84.96 pg/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in CG (H = 4.00, P < 0.05). The serum levels of T in Ovulatory period were 0.55, 0.45, 0.55 ng/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in DFPG (H = 6.47, P < 0.05), but no significant difference was observed between HFG and CG (H = 2.41, P > 0.05). The serum levels of GnRH in Luteal phase were 24.09, 20.16, 23.50 ng/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in DFPG (H = 14.14, P < 0.05) and CG (H = 12.53, P < 0.05). The serum level of E2 in luteal phase were 81.47, 64.60, 74.55 pg/ml in female from DFPG, HFG and CG respectively. It was lower in HFG than that in DFPG (H = 5.69, P < 0.05). As for LH, FSH and T, no significant differences were observed among the three groups (P > 0.05 respectively). The abnormal rates of E2 level were 22.73 (30/102), 37.93 (44/72), 20.26 (46/181) in female from DFPG, HFG and CG respectively. The E2 abnormal rate in female from HFG was higher that from DFPG (χ(2) = 6.82, P < 0.05) and CG (χ(2) = 12.38, P < 0.05).</p><p><b>CONCLUSION</b>Fluoride exposure may influence reproductive hormones in female, especially in ovulatory and luteal phase of menstrual cycle.</p>

Influence of polluted SY River on child growth and sex hormones / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the influence of the polluted SY River on children's growth and sex hormones, and provide scientific data for assessment of the polluted status of the SY River.</p><p><b>METHODS</b>The study areas were selected randomly from the SY River Basin. Lead (Pb), mercury (Hg), arsenic (As), phthalates (DEP, DBP, DMP, DEHP), and bisphenol A (BPA) were measured both in the river water and in the drinking water. School children were selected by cluster sampling (n=154). Physical development indexes (height, weight, bust-circumference, and skinfold thickness) and sex hormones [testosterone (T) and estradiol (E2)] were measured for all the children.</p><p><b>RESULTS</b>The contents of Pb and Hg exceeded Class V standards of surface water quality in each section of the river and other indicators exceeded Class III. Compared to the control area, the concentrations of Pb, Hg, As, BPA, DEP, and DBP in the drinking water were significantly higher than in the polluted area (P<0.05). Children from the control area had significantly lower E2 and T than children from the polluted area (P<0.05). Among anthropometric results, only skinfold thickness had statistically significant difference between the two groups (P<0.05), while the other indexes showed no significant differences between the two groups (P>0.05).</p><p><b>CONCLUSION</b>The drinking water has been polluted by the SY River and affected serum sex hormone levels of children living in the polluted area.</p>

Children's dental fluorosis and estrogen receptor α gene Xba I polymorphism / 中国地方病学杂志

Objectives To explore the relationship between polymorphism in estrogen receptor alpha (ERα)gene Xba I and child dental fluorosis.Methods Qiulou township of Kaifeng and Sunying township of Tongxu counties of Henan province were chosen as the investigation spots in 2006.An area of water drinking endemic fluorosis(high fluoride area)and a non-endemic area(control area)were chosen in every spot,where dental fluorosis of children aged 8 to 12 years old were examined and diagnosed by using the Dean method.The children in the high fluoride areas were divided into dental fluorosis group and control group of the endemic areas according to dental fluorosis status,and the children in the control areas as control gruop of non-endemic areas.The Xba I polymorphism in the ERα gene was genotyped using the PCR-RFLP procedure.The fluoride levels in the urine samples from the three groups were detected by fluoride ion selective electrode and over standard rate of the urine was counted.Results The prevalence rate of dental fluorosis in high fluoride areas was 51.7%(74/143)and the community fluorosis index was 1.310.No dental fluorosis case was checked out in the control and the community fluorosis index was 0.021.The over standard rate of urine fluoride in dental fluorosis group[84.6%(121/143)]was significantly higher than that of control in non-endemic area[9.6%(9/94);χ2=125.95,P<0.01].The frequency distribution of ERα Xba I genotype was XX 6.8%(5/74),xx 36.5%(27/74),xx 56.8%(42/74)in dental fluorosis group;XX 15.9%(11/69),Xx 37.7%(26/69),xx 46.4%(32/69)in the eontrol of the endemic areas;XX 14.9%(14/94),Xx 43.6%(41/94),xx 41.5%(39/94)in children from the control in non-endemic area,respectively.No significant difference was found among the three groups(χ2= 3.450, P > 0.05). Allele frequency of ERα Xba I genotypes was X 22.7%(30/132), x 77.3%(102/132) in dental fluorosis group and X 35.5%(39/110),x 64.5% (71/110) in the control in endemic area when urine fluorosis of children was exceeding standard and significant difference was found in this two groups(χ2 = 4.768, P < 0.05; OR = 0.535,95% CI:0.305 - 0.941). Conclusion Children who carried X allele frequency of ERα Xba I genotypes have a lower risk of dental fluorosis when children with high-loaded fluoride status.

Serum calciotropic hormone levels, and dental fluorisis in children exposed to different concentrations of fluoride and iodine in drinking water / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>This study provides an evidence that iodine exposure may modify the serum calciotropic hormone levels related to fluorine exposure.</p>

Study on the relationship between collagen type Ⅰ alpha 2, osteocalcin genes polymorphisms, serum calciotropic hormone levels and dental fluorosis / 中国地方病学杂志

Objectives To investigate the relationship between fluorosis polymorphisms in collagen type Ⅰ alpha 2 (COL1A2) and osteocalcin (OC) gene, and serum calciotropic hormone levels. Methods The children between 8 and 12 years of age in Kaifeng and Tongxu cities of Henan Province were chosen to be the object of observation. Accoding to situation of dental fluorosis, they were divided into three groups: dental fluorosis group, non-dental fluorosis group from high fluoride areas, and control group form the control areas. The Pvu Ⅱ and Rsa Ⅰ markers of COL1A2 gene as well as HindⅢ marker of OC gene were genotyped by PCR-RFLP procedure. Calcitonin and osteocalcin levels in serum were measured using radioimmunassays. Results The frequency distribution of COL1A2 PvuⅡ genotype was pp 49.3%(37/75), Pp 32.0%(24/75), PP 18.7%(14/75) in children with fluorosis; pp 43.5% (30/69), Pp 52.2% (36/69), PP 4.3%(3/69) in children without fluorosis from high fluoride areas; and pp 43.8% (42/96), Pp 40.6% (39/96), PP 15.6% (15/96) in the children without fluorosis from control areas respectively. Childrens with the homozygous genotype PP of COL1A2 Pvu Ⅱ had a significantly increased risk of dental fluorosis(OR=4.85, 95%CI: 1.22-19.32) compared to children with the homozygous genotype pp in anendemic fluorosis area. The frequency distribution of COLIA2 Rsa Ⅰ genotype was rr 50.7% (38/75), Rr 36.0% (27/75), RR 13.3%(10/75) in children with fluorosis; rr 46.4%(32/69), Rr 46.4%(32/69), RR 7.2%(5/69) in children without fluorosis from high fluoride areas, and rr 45.8% (44/96), Rr 45.8% (44/96), RR 8.3% (8/96) in the children without fluorosis from control areas respectively. There were no significant differences in the three groups (P>0.05). The frequency distribution of OC Hind Ⅲ genotype was hh 48.0% (36/75), Hh 34.7% (26/75), HH 17.3% (13/75) in children with fluorosis; hh 43.5% (30/69), Hh 43.5% (30/69), HH 13.0% (9/69) in children without fluorosis from high fluoride areas, and hh 47.9%(46/96), Hh 40.6%(39/96), HH 11.5%(11/96) in children without fluorosis from control areas respectively. There were no significant differences in the three groups (P>0.05). Additionally, fluoride levels in urine and OC levels inserum were found to be significantly lower in controls from non-endemic areas compared to cases(P<0.05). However, the differences in urine fluoride and serum OC levels were not observed when cases were compared to controls from high fluoride areas(P>0.05). Conehlsions This study provides the evidence of an association between polymorphisms in the COL1A2 gene with dental fluorosis in populations exposed to high fluoride. There were no correlation between OC Hind Ⅲ genotype and the dental fluorosis.