Toxic Effects Of BPA On The Mouse Reproductive And Endocrine System

Objective To observe the reproductive and endocrine system toxicity of Bisphenol A (BPA) and explore their possible mechanisms. It may offer the experimental and theoretical basis for the recognition of the long time damage and security estimate on the BPA. Methods 1. Experiment in vivo 130 healthy and mature Kunming mice were chosen in the experiment, weighing about 18-20 g, half male and half female. Fifty of them were randomly divided into 5 groups, 10 mice in each group, half male and half female. The mice were divided into one negative control group and other 4 different dosage groups. BPA dosage was 4 μmol/Kgwb, 20 μmol/Kgwb, 40 μmol/Kgwb and 80 μmol/Kgwb, respectively. The animas were injected intraperitoneally with different dosage of BPA, 0.8 ml/100 g body weight for 3 days. In the 4th day, the mice were sacrificed. Another 80 mice were randomly divided into 8 groups, 10 mice in each group, half male and half female. The mice were divided into negative group and other 7 different dosage group. The animals were injected intraperitoneally with 20 μmol/Kgwb BPA for one time, 0.8 ml/100 g body weight. They were sacrificed at 30 min, 4 h, 12 h, 24 h, 36 h, 48 h and 72 h respectively after there were injected with BPA. The animals in the negative control group were injected intraperitoneally with salad oil, 0.8 ml/100 g body weight. They were sacrificed 4 hours later. The enzyme activity of testis cell, testosterone level in male mice, estrogen level and glucose level in mice serum were measured. Pathological change of male mice testis and female mice uterus were observed. 2. Experiment in vitro Testis cell suspension in mice were prepared and administrated with different dosage of BPA for 1 hour. One hour late, testis cell survival rate and DNA damage in mice were measured. Results 1. Effects of BPA on the survival rate in mice testis cells. The testis cell survival rates of the negative control group were clearly higher than those in the solvent control group and different dosage of BPA groups (P<0.05). There was no difference between the solvent control group and the 10-8 mol/L group (P<0.05), while those in the solvent group were higher than different dosage of BPA groups (P<0.05). 2. Effects of BPA on DNA damage in mice testis cells The ratio of tail tailings in different dosage of BPA groups were significantly higher than that in the negative control group (P<0.05) except the 10-10 mol/L group (P>0.05); except the ratio of tail tailing in 10-10 mol/L group was lower than the solvent control group (P<0.05), the others were higher than it (P<0.05). The DNA damage level in the mice increased with the increasing of the BPA dosage (P<0.05). Ⅳgrade DNA damage were found in the 10-5 and 10-6 mol/L group. 3. Effects of BPA on the organ indices in mice The testes index in different dosages of BPA group were clearly higher than those in the negative control (P<0.05). The uterus index in the 4 μmol/Kg and 20 μmol/Kg group were clearly higher than that in the negative control (P<0.05). The uterus index in the 20 μmol/Kg group was clearly higher than that in the 40 μmol/Kg and 80 μmol/Kg group (P<0.05). The hypothyroid index of different dosages of BPA were clearly higher than those in the negative control (P<0.05) and it recovered by and by with the increasing of the BPA dosage. The kidney index changed little (P>0.05). 4. Effects of BPA on the enzyme activity in mice testis cells 4.1 Effects of different dosage of BPA on the enzyme activity in mice testis cells: The LDH activity in different dosage of BPA groups was clearly lower than that in the negative control (P<0.05) and it increased along with the increasing of the BPA dosage. The G-6-PD activity in the 4 μmol/Kg group was clearly higher than that in the negative control. There was no difference between the negative control and other dosage groups (P>0.05). 4.2 Change of enzyme activity in mice testis cells at different time: LDH activity increased with the increase of the time and got the top at 4 hour. It began to decline after the 4th hour and changed little between 12 to 24 hour and then declined after 25 hour. After 48 hour, it recovered to the normal level and kept the balance. G-6-PD activity has been increasing from 0.5 hour to 12 hour and got the top level after the 12th hour and then it began to decline. After 36 hour, it recovered to the normal level and kept the balance conditions.5. Effects of BPA on testosterone level in male mice testis 5.1 Effects of different of dosage BPA on the testosterone level in male mice testis tissue: testosterone in different BPA dosage group was clearly lower than that in the negative control, and it decreased along with the increasing of BPA dosage (P<0.05). There was no difference among the different dosage of BPA groups (P>0.05). 5.2 Change of the testosterone level in the male mice testis tissue at different time: after the mice were injected with BPA for 0.5 hour, testosterone concentration in the mice declined quickly compared with the negative control (P<0.05). 4 hour later, it still was clearly lower than that in the negative control. After that time, it recovered by and by and got the normal level at 12 hour and then went on rising and got the top at 24 hour. After 36 hour, it resumed to the normal level and kept the balance. 6. Effects of BPA on the estradiol level in mice serum 6.1 Effects of different dosage of BPA on the estradiol level in mice serum: the estradiol concentration of the 4 and 20 μmol/Kg group was clearly lower than that in the negative control (P<0.05). Estradiol level in the 80 μmol/Kg group was clearly higher than that in the negative control. There was no difference between the negative control and the 40 μmol/Kg group. The estradiol concentration of the 40 and 80 μmol/Kg group in female mice was significantly higher than that in the negative control and the 4 μmol/Kg, 20μmol/Kg group (P>0.05). 6.2 Change of the estradiol level in the mice serum at different time:after 0.5 hour, the estradiol level in the male mice decreased which was lower than the normal level at 4 hour. Then it went on decreasing and got the bottom at 12 hour and increased by and by after that time. At 36 hour, it got the top level (P<0.05). Then it decreased and resumed to the normal level at 72 hour.Change of the estradiol level in the female mice serum: the estradiol level in serum declined quickly and got the bottom at 4 hour after the mice were injected with BPA. After that, it rose gradually and resumed to the normal level and increased slowly. 7. Effects of BPA on glucose level in mice serum 7.1 Effects of different dosage of BPA on the glucose level in mice serum: after the mice were injected with BPA, the serum glucose level of the 4 and 80 μmol/Kg group were clearly lower than that in the negative control (P<0.05). The serum glucose level of the 20 μmol/Kg group was clearly higher than that in the negative control (P<0.05). There...