The Influence Of Fluoride Exposure And Estrogen Receptor Alpha Gene Polymorphisms On Reproductive Hormones In Male

ObjectiveThe aim of this study was to explore the influence of water fluoride exposure onreproductive hormones and the interaction between fluoride exposure and geneticsusceptibility on reproductive hormones in male. It will provide the basic evidencefor the molecular mechanism of the influences of fluoride exposure on reproductivehormones in male.Materials and methodsCross-sectional study was conducted in2011-2012in seven villages of a countyin Henan province including two high fluoride villages, two defluoridation projectvillages (the defluoridation project has been carried on in the end of2008) and threecontrol villages based on the fluoride concentration in drinking water. Men who wereborn and growth in the villages and aged18-50years old were recruited using clustersampling. They were divided into high fluoride group (HFG,90subjects),defluoridation project group (DFPG,79subjects) and control group (CG,179subjects)in accordance with the above villages. All subjects accepted questionnaire andphysical checkup. Fasting blood and morning urine samples were collected. Theconcentration of fluoride in urine was determined by fluoride ion selective electrodemethod. The serum level of GnRH was detected using enzyme linked immunosorbentassay (ELISA). The serum levels of LH, FSH, E2and T were determined bychemiluminesence immune assay (CLIA). The PvuⅡ (rs2234693) and XbaⅠ(rs9340799) polymorphisms in the estrogen receptor α gene were genotyped using thePCR-RFLP procedure and rs3798577polymorphism was genotyped using TaqMan○RMBG probes Real-Time PCR procedure. All analyses were performed using the SPSS21.0software.Results1. The influences of fluoride exposure on serum hormone levels of hypothalamus-pituitary-goand (HPG) axis in male.There were significant differences of GnRH, FSH, E2, T, ABP, and SHBGamong three groups. Serum levels of GnRH and ABP in male from HFG weresignificantly lower than that from CG (P<0.05respectively). Serum levels of FSHand E2in male from HFG were significantly higher than that from DFPG and CGrespectively (P<0.05), serum T level in male from HFG was significantly lower thanthat from DFPG and CG respectively (P<0.05). Serum SHBG level was significantlylower from HFG and DFPG than that from CG (P<0.05respectively).2. The influence of fluoride exposure and ERα gene polymorphisms on serumhormone levels of HPG axis in maleIn HFG, serum T level in male carrying pp genotype of ERα Pvu Ⅱwassignificantly higher than that in male carrying Pp genotype (P<0.05); serum FSHlevel in male who carried ERα rs3798577T/T genotype was significantly higher thanthat in male who carried C/T and C/C genotypes (P<0.05respectively). In DFPG,serum level of FSH in male carrying ERα PvuⅡ pp genotype was higher than that inmale carrying PP and Pp genotypes (P<0.05respectively); serum ABP level in malewho carried ERα Xba Ⅰ Xx genotype was significantly lower than that in male whocarried XX and Xx genotypes (P<0.05respectively); serum level of SHBG in malewho carried xx of ERα Xba Ⅰ genotype was significantly higher than that in malewho carried Xx genotype (P<0.05). Serum levels of GnRH in male carrying ERαPvuⅡ Pp,ERα XbaⅠ xx andERα rs3798577C/T genotypes in HFG weresignificantly lower than that in DFPG and CG who carried the same genotypes(P<0.05respectively), and serum GnRH in male who carried ERα rs3798577C/Cgenotype in HFG was significantly lower than that in CG who carried the samegenotype (P<0.05). In DFPG, serum FSH levels in male carrying ERα Pvu ⅡPP andPp genotypes were significantly lower than that in CG who carried the samegenotypes (P<0.05respectively), but serum FSH level in male who carried ERαrs3798577T/T genotype in HFG was significantly higher than that in DFPG and CGwho carried the same genotype (P<0.05respectively). Serum E2levels in male fromHFG carrying different genotypes in ERα PvuⅡ, XbaⅠ and rs3798577weresignificantly higher than that in male from CG carring same genotypes except for carrying ERα rs3798577T/T genotypes (P<0.05respectively); serum T level in malewho carried ERα PvuⅡ Pp genotype in HFG was significantly lower than in DFPGand CG (P<0.05respectively). Serum levels of ABP in male carrying ERα XbaⅠ xxand ERα rs3798577T/T genotypes in HFG were significantly lower than that in CGcarrying the same genotypes (P<0.05respectively). Serum level of SHBG in malewho carried different genotypes of ERα PvuⅡ, XbaⅠand rs3798577except for xxand C/C in HFG was significantly lower than that in CG. However, serum SHBGlevel in male who carried xx genotype of ERα XbaⅠ was significantly higher thanthat in CG (P<0.05).Conclusion1. Long term fluoride exposure in drinking water could influence on serum HPGaxis hormone levels and related protein levels in male. Serum GnRH, T, ABP andSHBG levels may decrease and serum FSH, E2levels may increase.2. Interaction between fluoride exposure and ERα polymorphisms could affecton the serum hormone levels of HPG axis. Serum GnRH levels in male who carriedERα PvuⅡ Pp and ERα XbaⅠ xx genotype, serum FSH and E2levels in male whocarried ERα rs3798577T/T genotype, serum T level in male who carried ERα PvuⅡPp genotype, serum ABP levels in male who carried ERα XbaⅠ xx and ERαrs3798577T/T genotype, and serum SHBG level who carried ERα XbaⅠ xxgenotype may be more susceptible to fluoride exposure.