The Disruption Of BDE-209 And DEHP Exposure To Maleadolescent Mice Reproductive And Endocrine

Objective:To observe the adolescent male ICR mice male reproductive damaged by the Decabromodiphenyl ether(BDE-209) and 2-(Diethylhexyl)phthalate(DEHP) combined exposure, and explore the mechanism primarily that BDE-209 and DEHP combined exposure down-regulate the testis testosterone synthetas and lead to male reproductive damage. MethodThe male reproductive damaged model was established via administration of BDE-209 and DEHP by oral to 4 weeks adolescent male ICR mice. After 1 week adaptive breeding, dividing the 60 mice into 5 groups: A, corn oil; B, 100mg/kg/d PBDE-209+100mg/kg/d DEHP; C, 100mg/kg/d PBDE-209+300mg/kg/d DEHP; D, 300mg/kg/d PBDE-209+100mg/kg/d DEHP; E, 300mg/kg/d PBDE-209+300mg/kg/d DEHP. The mice were free diet and drink, room temperature was about 20-25℃, humidity was 50%±10%, bright and darkness was 12h/12 h. The mice exposure 6 times per week for 6 weeks. The mice were sacrificed after treatment, tissue were separated under the ice, measured body and tissue weight and preserved into-80℃ fridge. Work out the mice sperm’s number and test the testosterone by radioimmunoassay. Observe the testis and epididymis histomorphology and ultrastructure by light microscope and electron microscope. Detect the St AR and P450 scc location by immunofluorescent assay. The St AR, P450 scc, 17β-HSD and PKA expression was measured by western blot. ResultsThere is no significant general condition difference among the groups, while the E group mice testicular coefficient(0.3001±0.0771) was significantly decreased by the combined exposure compared to the control group(0.3774±0.0395). The serum testosterone was decreased by the combined exposure A(2.89±0.57), B(2.59±0.63), C(2.68±0.16), D(2.14±0.84), E(2.06±0.67). The sperm’s number((×106/m L)) was decreased by the combined exposure A(57.25±10.08), B(43.18±13.55), C(35.33±9.45), D(31.87±11.69), E(19.67±2.08). Under the light microscope, observed the combined exposure damaged the mice testis seminiferous tubule structure and decreased the tubule diameter, and decreased the number of Sertoli cell, Leydig cell and spermatogonium, the spermatogonium were disorganized and decreased the sperm number in the seminiferous tubule. Under the electron microscope, observed that the sperm structure was normal and the mitochondria of the sperm was integrated in the control group, while the combined exposure damaged the epididymis and sperm structure, found sperm shape abnormality and the pipe of ductus epididymidis fibrosis. Immunofluorescent assay found that the combined exposure decreased the fluorescence intensity of St AR and P450 scc compared to the control group; western blot found that the combined exposure decreased the expression of St AR, P450 scc and 17β-HSD. Western blot found combined exposure decreased the expression of PKA. ConclusionThere is reproduction toxicity that the adolescent male ICR mice combined exposure to BDE-209 and DEHP. The combined exposure damaged the mice testis and epididymis structure, decreased the serum testosterone, sperm number and testosterone synthetase expression and location. Down-regulation of testicular testosterone synthetase mediated the decrease of testosterone synthetase induced by the BDE-209 and DEHP combined exposure could lead the male reproduction impairment.