Study Of Decabrom Odiphenylether On Increasing Of MAPKs Pathway Proteins And Damage Of BTB

ObjectiveTo study the changes of the expression of MAPKs pathway related protein and BTB tight junction protein Claudin-11, the ultrastructure of BTB when the male ICR mice exposed decabromodiphenyl ether(BDE-209) during adolescence. In addition, after Sertoli cell lines Ser W3 exposed different concentration BDE-209, the expression of MAPKs pathway related protein and BTB tight junction protein Claudin-11 were dtected too. For further research on male reproductive toxicity mechanism of BDE-209 provide a scientific basis. MethodsIn vivo, 52 four-week-old mice, 15~21g, adaptive feeding for one week. Then divided into 4 groups stochasticly, namely solvent control group, low-dose group(100 mg/kg BW), middle-dose-group(300 mg/kg BW) and high-dose-group(500 mg/kg BW), each group for 13. Mice were treated BDE-209 by gavage, sacrificed after 6 weeks, separated organ on ice, weighed and then stored at-80℃. Testicular tissues were observed by light microscopy through HE staining and electron microscopy ultrastructure. Western Blot was used to detect the expressions of MAPKs pathway related protein(p38, p-p38, ERK, p-ERK, JNK, p-JNK) and BTB tight junction protein Claudin-11.In vitro, testis sertoli cell lines Ser W3 were exposed in different concentrations of BDE-209(0μg/ml, 10μg/ml, 20μg/ml, 30μg/ml, 40μg/ml). After 24 h, Morphological changes were observed. MTT method was used to detect cell survival percentage, LDH assay was used to detect lactate dehydrogenase toxicity, Western Blot method was used to detect the expressions of MAPKs pathway related protein(p38, p-p38, ERK, p-ERK, JNK, p-JNK) and BTB tight junction protein Claudin-11. ResultsAfter exposing BDE-209 for six weeks, all the male ICR mice were slow weight gain, from the beginning of the third week, compared with the solvent control group, the body weight of middle-dose-group and high-dose-group were statistically difference(P<0.05), the coefficient of testis and epididymis decreased obviously(P<0.05).The results of HE staining of testicular tissue showed that, with the dose increasing, the number of sertoli cells and the number of sperm in the seminiferous tubules reduced obviously, cell arrangement was not closely, widening gap between sertoli was widened, leydig cells gap was widened, spermatogenic cell gap increased, the number of sertoli cell, spermatogenic cells and leydig cells were reduced significantly. The results of ultrastructure showed that, compared with the solvent control group, sertoli cell tight junction disintegration and fracture were observed clearly in treated groups. Both in vivo and in vitro, all the ratios of MAPKs pathway p-p38/ p38 and p-JNK/ JNK were increased significantly(P<0.05), and the expression of BTB tight junction protein Claudin-11 was reduced significantly(P<0.05). ConclusionBDE-209 can increase the expression of MAPKs pathway related protein and decrease the expression of BTB tight junction protein Claudin-11 in testicular tissue and Sertoli cell lines Ser W3, and damage the ultrastructural of Sertoli cells BTB tight junction, suggesting that BDE-209 may damage the Sertoli cells BTB by MAPKs pathway.