The Effects Of Bisphenol A On Reproductive System Of Male Rats During Puberty And Its Mechanism

Objective:The research of bisphenol A (BPA), a well-known environmental estrogenic compound on reproductive function has become a hotspot in recent years. BPA exposure can lead to adverse effects at all levels in male reproductive system. In addition to have a role in simulating estrogen, other mechanisms are not very clear. When estrogen receptor activity blocked, BPA still produces toxic effects. It indicates there are other ways to injury in male reproductive system. Androgen receptor (Androgen Receptor, AR) plays an important role in the process of development and maturity of male reproductive organ. Whether BPA can influence male reproductive system by affecting the expression or activity of AR, is a question worth exploring. Whether BPA exposure at the beginning of the growth and development can lead to a more serious injury than those of the individual mature? Whether endocrine regulatory function is the key to toxic effects of BPA? In this study adolescent rats were observed the effects of them on the development of genital organs of male rats by exposed to BPA and estradiol (E2), studied gene expression of AR mRNA in testis and prostate by QRT-PCR method in order to explore the role of AR in the process and provide of toxicological basis to prevent the adverse effects of BPA on human reproductive function. The results of this study will provide detailed and reliable toxicological data to prevent environmental endocrine disruptors on human health effects and take effective measures.Method:Three-week-old Wistar male rats were provided by the Experimental Animal Center of Shenyang Medical College, housed in barrier environment, at which the temperature was controlled at 23 ~ 25℃, humidity controlled at 57% ~ 60%, light 12h: 12h day and night cycle, feeding to meet the national standard of ordinary feed, drinking water treatment by filtration sterilization. According to the principle of equality the experimental animals were randomly divided into five groups of 10, respectively, corn oil control group, BPA at 50,100, 200 mg / kg group, estradiol (E2) 100μg/kg group. BPA and E2 were first dissolved with anhydrous ethanol, and then diluted to the required concentration of corn oil. BP A, corn oil and E2 were exposed for 6 weeks at 2ml/kg volume by subcutaneous injection. BPA was exposed four days (Mon, Tue, Thu, Fri) a week. During the experiment, rats were freely fed, drunk, light for 12 hours day and night cycle, temperature was controlled at 23 ~ 25℃, humidity at 57 ~ 60%. E2 group was exposed estradiol 100μg/kg 6 weeks, 4 days a week (Mon, Tue, Thu, Fri) by subcutaneous injection. Control group, the same amount of corn oil by subcutaneous injection. Daily morning weighing and injection subjects were done. After six weeks exposed to subjects, animals were treated by ether anesthesia, abdominal aortic blood was obtained and serum was separated.Results:The results of this study show that the total number of sperm, sperm motility rate of 200mg/kg and the E2 group was significantly lower than the control group. Sperm deformity rate in each group compared with the control group increased slightly without statistical significance. Bisphenol A and estradiol exposure for 6 weeks influenced the weight of genital organs. The weights of epididymis, seminal vesicles, prostate at the various treated groups compared with the control group were the significant differences. Testicular at 200mg/kg group and E2 was significant difference compared with control group (P<0.05). The organs coefficient of seminal vesicles, prostate had decreased tendency with increasing dose. Thereinto, the organ coefficients of prostate, seminal vesicles in each treated group had a significant difference compared with the control group (P<0.05 or P <0.01), the organ coefficient of epididymis at 200mg/kg and E2 groups had a significant difference compared with the control group (P<0.05). The serum testosterone level decreased significantly at 200mg/kg and E2 groups compared with the control group (P <0.05). The serum estradio level was increased significantly at E2 group compared with the control group. The gene expression of AR, ERα, ERβin testicular and prostate were detected. The results showed that the mRNA expression of AR, and ERβin the testis had no difference compared with the control group, the mRNA of ERαat 100mg/kg, 200mg/kg and the E2 groups was decreased significantly compared with the control group; the mRNA expression of AR and ERαin the prostate increased significantly and the mRNA of ERβin the prostate decreased significantly at E2 group compared with the control group.Conclusion:1. Peripubertal exposure to Bisphenol A could decrease the sperm count,sperm motility,organ weight and organ coefficient and induce pathological change of prostate,seminal vesicle gland and epididymis,then result in dysfunction of reproductive function.2. Peripubertal exposure to Bisphenol A could decrease the testosterone level in the blood, then result in dysfunction of spermatogenesis.3. The growth and development of testis and prostate was affected exposure to high dose of Bisphenol A.