Effects Of BPA Exposure On Male Sex Hormones And Sperm Quality

Objective:Bisphenol A(BPA),a kind of environmental estrogens material which chemical structure is similar to estradiol,is one of the highest production of chemicals in the world. It have weak estrogenic activity and strong resistance to androgen activity. Studies have found that BPA can be released from BPA related products and enter into the body through food or drinks,it can damage reproductive、nervous、 immune and other systems,male reproductive system has been become one of the research hot spots. Production of sperm is an important function of the male reproductive system, only the fertilization of the normal、healthy sperms and eggs can produce healthy offspring.FSH and T play an improtan role in maintaining reproductive function、the normal development of gonad and initiating、maintaining sperm production process.And the physiological functions of FSH and T are mediated by their receptors(FSHR、AR).Therefore, normal sex hormone levels and the integrity of their receptor’s expression and function are very important to male reproductive function. At present,the researchs in population about the effect of BPA on male sex hormone levels and sperm quality are very little, and the reports about the effects of BPA on hormone receptors have not seen.So,this study adopts the method of combining people and animals to explore the effects of BPA on sex hormone、 hormone receptors and sperm quality,providing the new train of thought for exploring the function and mechanism of BPA on reproductive function.Methods:1.Population-based study:Exposure group subjects were chosed the male works who were worked in the epoxy resin factory in yueyang、ningbo、wuxi and yixing of china from2004to2008.They were exposured to BPA at least one year and still on the job when we investigated.Chosed the male works who didn’t exposure to BPA occupationally in water and weacing factorys which are in the same places of exposure group in2004-2008as controls.These factories’production history were similar to epoxy resin factory of exposure groups.The two groups were matched on the characteristics of the place of residence、age、work years and national by frequency matching. Objects’s data,such as general conditions、living habits、work history of exposure were collected through structured questionnaire. Objects’s fasting morinng of venous blood and semen specimens were also collected. The level of serum bisphenol A was detected by HPLC and the levels of FSH、T were detected by RIA.Sperm vitality、survival rate and density were detected by CASA,the analysis of sperm morphology was analysed by improbed pap staining. The data were analyzed by SPSS17.0. Normal distribution data were examined by t-test and ANOVA. Skewness data were examined by Wilcoxon or Kruskal-Wallis H test. Categorical variables were examined by χ2test. Pearson method were used to analy the relationship.2.Animals experiments:35male Wistsr rats which aged4weeks were divided into five groups randomly, including negative control group、BPA50mg/kg、BPA100mg/kg、BPA200mg/kg and positive control group, infected BPA with1ml/100g through stomach four weeks continuously.After4weeks,gathered and weighed the epididymis and testes,calculated the viscera coefficient.Collected blood by cardiac apex and detected the levels of FSH、T by RIA. Sperm motility、survival rate and density were detected by CASA,and the analysis of sperm morphology through improbed pap staining.The expression levels of mRNA and protein of FSHR、AR were detected by real-time PCR and Western blot respectively. Results:1.The effects of BPA occupational exposure on male sex hormones and sperm quality.(l)The detection rates and the level of serum BPA in exposure group are significant higher than the control group(P<0.05).Compared with the recent exposure group,the level of serum BPA is significant lower of long-term exposure group (P<0.05)(2)The difference was no significant of T level between exposure and control grouop (t=2.228,P>0.05).Compared with the control group,the level of FSH was higher in exposure group.Among BPA<0.139μg/L、0.139μg/L<BPA<12.570μ/L BPA>12.570μug/L in exposure group,there were no significant difference of FSH、T levels.Compared with the recent exposure group,the level of FSH was higher in long-term exposure group (t=-3.846,P<0.001) while there was no difference of T level between the two groups (t=1.021,P=0.309)(3)Compared with control group, sperm survival rate and vitality were lower in exposure group(P<0.05).There were no differences of sperm abnormity rate and density between the two groups. Among BPA<0.139μug/L0.139μg/L<BPA<12.570μg/L. BPA>12.570μg/L in exposure group,the difference of sperm survival rate are significant (H=29.893,P<0.001) while the differences of sperm abnormity rate、vitality and density were unsignificant(P>0.05).With BPA concentration increased,sperm survival rate decreased,it showed negative correlation between them (r=-0.338,P<0.001). Compared with recent exposure group,sperm survival rate and vitality are higher in the long-term exposure group(P<0.05).The differences of sperm abnormity rate and density were unsignifant(P>0.05).2. Effects of BPA on sex hormones and sperm quality of male rats(1)With the increasing of BPA infected doses and time.the speed of rat body weight growth was slowing down,and the weight and body weight growth became lower after infecting BPA,especially in the high dose group of BPA.Compared with the negative control group,testicular viscera coefficient is lower in medium and high dose groups of BPA while epididymis viscera coefficient is lower in high dose group.(2)Infecting with BPA can cause sperm vitality、survival rate and density reduced.Compared with the negative control group, sperm vitality and survival rate are lower in BPA medium and high groups while sperm density is lower in BPA high group,but BPA can’t affect sperm abnormity rate.(3)Compared with the negative control group,the level of T is lower in BPA medium and high groups while FSH is higher in BPA high group,the differences are significantly(P<0.05).(4)Compared with the negative control group,the level of mRNA of is lower in BPA medium and high groups while the level of protein is lower in BPA high group of AR.The level of mRNA and protein of FSHR in BPA high group are lower than the negative control group.Conclusions:1. Occupational exposure of bisphenol A can cause increases of serum BPA level. Prolonged not exposure to BPA, the level of serum bisphenol A can be reduced because of the metabolic mechanism of BPA.2. Occupational exposure of Bisphenol A can disorder the level of FSH and this interfere may be irreversible, it can not be restored with the decrease of serum BPA concentration.But that effect of BPA can not be further aggravated with the increasing of serum BPA concentration.3. Occupational exposure of bisphenol A can reduce men’s sperm quality, and it have certain toxic effects on male fertility. The impact on sperm survival rate and vitality are more significant. With the metabolic clearance of BPA in the body, sperm survival rate and vitality can restore gradually, showing reversibility.4. Bisphenol A gavage can reduce the growth rate and increment of rat weight, and reduce the coefficient of testis and epididymis viscera significantly, suggesting that a certain concentration of BPA will have toxic effects on rat reproductive development and the gonads,which can make growth and development speed slowly and gonad dysplasia.5. Bisphenol A gavage can lead to rats’sperm quality reduced, manifesting as the decreases of sperm vitality、survival rate and density.lt is harmful to male reproductive.6. Normal levels of sex hormone can be interfered by the bisphenol A gavage, expresenting serum T levels decrease and FSH levels rise.7. mRNA and protein levels of FSHR, AR in testicular tissue can be decreased by Bisphenol A, which make sex hormones can’t play normal physiological role,so as to affect the process of spermatogenesis and reducing sperm quality.