| ObjectiveBPA is an environmental estrogen and an important additive of the plastics industry used in the production of polycarbonate, epoxy and polystyrene resins BPA is also widely used in the food-packaging industries. BPA may infiltrate from coatings of containers into foods and from dental materials into the saliva of patients. Biologic effects of BPA had been proven to be induced by interacting with estrogen receptors, including estrogen, androgen, thyroxin, adrenalin, insulin etc. Increasing evidence suggests that they are related to reproductive and developmental disorders, abnormal metabolism and increasing risk of some cancers in human. The incidence of male dysgenesia has been on the rise in many countries during the last few decades, including increasing incidences of short and small penis, testicular atrophy, cryptorchidism, hypospadias, declining sperm number and semen quality, increasing sperm aberration rate, increasing apoptosis of spermatogenic cells and sertoli cells etc. The present experiment observed the changes of sperm and testicle in some indexes when mice were treated by different doses of BPA. This experiment was to study the effects of BPA on the reproductive function of male mice, discover the possible mechanisms of its reproductive toxicity, look for the earlier signs of it's toxic influence and evaluate it's biological effects completely. MethodsWe selected 84 healthy mature male Kunming mice, which weighted18~20g each and were divided into four groups randomly: control group(0 umol/kg), low dose group(250 umol/kg), medium dose group(500 (xmol/kg) and high dose group(1000 u mol/kg), Each group had 7 mice. BPA of different concentration was used in the experiment with corn oil as a solven. The mice were exposed to BPA by intraperitoneal injection for 5 days, then the mice were chosen and killed in random after exposed to BPA for 1, 14 and 35 days. The blood was collected from the mice eyeball. After separating serum, MDA content, SOD and GSH-PX activity, and the weights of testicles, testicle coefficient, NO content and NOS activity in testicle were measured. We observed the cell cycle progression and the apoptosis of testicle cells, made the testicle tissue into pathology slice to observe pathological changes of the testicle tissue. Results 1 BPA could induce lipid peroxidation in male mice.The activities of SOD and GSH-PX in sperm significantly decreased with dose increasing of BPA, the content of MDA in sperm, the content of NO and the activity of NOS in testicle tissue remarkably increased with dose increasing. 7 days after exposure to BPA, the activity of SOD and the content of MDA in sperm of medium dose group and high dose group were obviously different compared with control group(P<0.05). The activity of GSH-PX in sperm of all dose groups were obviously different compared with control group(P<0.05). The content of NO and the activity of NOS in testicle tissue of high dose group were markedly. different compared with control group (P<0.05). The activity of SOD in sperm of medium dose group and high dose group were obviously different compared with 250 p.mol/kg group (P<0.05).The content of MDA in sperm of high dose group was evidently different compared with 250 umol/kg group (P<0.05). The activity of GSH-PX in sperm of all dose groups were apparently different compared with 250 umol/kg group (PO.05). The activity of GSH-PX and the content of MDA in sperm of high dose group were significantly different compared with 500 umol/kg group (PO.05). 14 days after exposed to BPA, the activities of SOD and GSH-PX in sperm of medium dose group and high dose group were remarkably different compared with control group (PO.05). The content of MDA in sperm of all dose groups were obviously different compared with control group (PO.05). The content of NO in testicle tissue of high dose group was markedly different compared with control group (P<0.05). The activity of SOD in sperm of high dose group was apparently different compared with 250 umol/kg group (PO.05). The activity of GSH-PX and the content of MDA in sperm of medium dose group and high dose group were evidently different compared with 250 umol/kg group (.P<0.05). The content of NO in testicle tissue of high dose group was apparently different compared with 250 umol/kg group (PO.05). The activity of GSH-PX and the content of MDA in sperm of high dose group were significantly different compared with 500 umol/kg group (PO.05). The activity of SOD in sperm of high dose group and the activity of GSH-PX of all dose groups were lower on the 7th day. The content of MDA in sperm of high dose group was higher on the 14th day. The indexes that we observed above were remarkably different between the 7th day groups and the 14th day groups (PO.05) after exposure to BPA. Thus BPA could decrease the activity of anti-oxidase and increase the content of lipid peroxidation product, break the balance between the oxidation system andanti-oxidation system, decrease their protection and induce lipid peroxidation to the body.2 The effects of BPA on cell cycle progression and apoptosis of the testicle cells in male mice.The percentage of cells at Go/Gi, S phases evidently decreased and the cell percentages of G2+M phase, the apoptosis of testicle cell apparently increased with dose increasing. 7 days after exposure to BPA, the percentage of cells at Go/Gi phase of medium dose group and high dose group were significantly different compared with control group(P<0.05). The percentage of cells at S phase of high dose group was remarkably different compared with control group (PO.05). The cell percentages of G2+M phase of all dose groups were obviously different compared with control group (P<0.05). The apoptosis of testicle cell of medium dose group and high dose group were evidently different compared with control group (PO.05). The percentage of cells at Go/Gi, S and G2+M phases of high dose group were markedly different compared with 250 umol/kg group (P<0.05). The apoptosis of testicle cell of medium dose group and high dose group were apparently different compared with 250 umol/kg group (PO.05). The percentage of cells at G2+M phases and the apoptosis of testicle cell of high dose group were significantly different compared with 500 umol/kg group (P<0.05). 14 days after exposed to BPA, the percentage of cells at Go/Gi, S phase of medium dose group and high dose group were obviously different compared with control group(/)<0.05). The cell percentages of G2+M phase of all dose groups were remarkably different compared with control group (P<0.05). The apoptosis of testicle cell of medium dose group and high dose group were evidently different compared with control group (P<0.05). The percentage of cells at Gq/G|, S and G2+M phase of high dose group were markedly differentcompared with 250 umol/kg group (PO.05). The apoptosis of testicle cell of medium dose group and high dose group were significantly different compared with 250 umol/kg group (P<0.05). The percentage of cells at Go/Gi, S, G2+M phase and the apoptosis of testicle cell of high dose group were remarkably different compared with 500 umol/kg group (PO.05). There were no obviously difference between the 7th groups and the corresponding 14th groups on cell cycle progression and apoptosis of the testicle cells (P>0.05). It suggested that BPA could promote the apoptosis of testicle cell and interfere the cell cycle Progression.3 The influence of BPA on testicle coefficient, sperm number, movable sperm percentage and sperm aberration rate in male mice.35 days after exposed to BPA, the testicle coefficient, the sperm number and the movable sperm percentage decreased with increased BPA, while the sperm aberration rate significantly increased. The testicle coefficient of all dose groups were remarkably different compared with control group (PO.05). The sperm number and the sperm aberration rate of medium dose group and high dose group were obviously different compared with control group (P<0.05). The movable sperm percentage of high dose group was remarkably different compared with control group (PO.05). The testicle coefficient and the sperm number of medium dose group and high dose group were evidently different compared with 250 umol/kg group (PO.05). The movable sperm percentage of high dose group was apparently different compared with 250 umol/kg group (PO.05). The testicle coefficient of high dose group was markedly different compared with 500 umol/kg group (PO.05). The testicle was the most impressionable sign of reproductive toxicity, such as the structure and function of the testicle were destroyed, thus influenced the testicle coefficient. This showed that BPA could go through theblood-testis-barrier and interfere the growth and development process of sperms. The percentage of movable sperms decreased, which was possibly related to the energy metabolism hold-back of sperms, and the increasing of abnormal sperm number significantly. 4 The pathological changes of testicle tissue in male mice.Having observed the pathological changes of testicle tissue in the experimental groups 35 days after exposure to BPA, we found the focal spermatogenic cells separated from basilar part on the surface of the testis, sertoli cells separated from spermatogenic cells, spermatogenic cells arranged in disorder and displacement of spermatogenic cells away from the basement membrane of seminiferous tubules as well as the flocculated chromatin of nuclei in sertoli cells and spermatogenic cells. Sertoli cells quantities reduced, thus it decreased its action to spermatogenic cells and influenced generating and growing of the sperms. ConclusionsThe current study showed that exposure to BPA could cause the activity decline of SOD and GSH-PX, the content increasing of MDA. The content of NO and the activity of NOS decreased in testicle tissue. BPA could change cell cycle progression and increase the apoptosis rate of testicle cell. BPA could decrease sperm number, the percentage of movable sperms, testicle coefficient and increase the rate of sperm aberration, cause the pathological changes of testicle tissue. It suggested that BPA could cause the reproductive toxicity in male mice and may related to the lipid peroxide.
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