title: [Effects of extracellular regulated protein kinases protein and impairment of blood testis barriar stucturein of mice with exposure to decabromodiphenyl ether].
abstract: Objective:To study changes in expression of claudin-11 and proteins related to mitogen-activated protein kinase (MAPK) signaling pathways, as well as the ultrastructure of the blood testis barrier (BTB), in male ICR mice exposed to decabromodiphenyl ether (BDE-209).Methods:Fifty-two mice, 4 weeks of age, weighing 15-21 g, were provided with adaptive feeding for 1 week. Mice were randomly divided into 4 groups, named control, low-dose, medium-dose and high-dose groups. The treated groups received BDE-209, by intragastric gavage, at doses, respectively, of 100, 300 and 500 mg/kg. Mice were sacrificed after 6 weeks and organs harvested on ice, weighed and stored at -80 °C. The ultrastructure of testicular tissues was examined by electron microscopy. Western blotting was used to detect proteins related to the MAPK pathway, including p38 mitogen activated protein kinase (p38), phosphorylated p38 (p-p38), extracellular regulated protein kinase 1/2 (ERK1/2) , phosphorylated ERK1/2 (p-ERK1/2) , c-jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK) and the BTB tight junction protein claudin-11. Analyze the difference between each groups.Results:At sacrifice, the body weights in each treated group were compared with those in the control group weighing (41.14 ± 0.60) g. Compared with controls, body weights were significantly different (P<0.05) in the middle dose, at (39.97 ± 0.66) g and high dose, at (39.98± 0.55) g in control group. The coefficients of the testis were significantly lower (P<0.05) in each treated group than in controls, with values of (0.37±0.0)%, (0.31±0.05)% and (0.31±0.04)% for low-dose, medium-dose and high-dose groups, respectively. The epidymus coefficient values were also significantly lower than controls (P<0.05), with values of (0.16±0.06)%, (0.11±0.05)% and (0.07±0.03)%, respectively in the same three dose groups. Electron microscopy ultrastructure showed that, compared with the control group, the testes in the middle and high dose groups had closely connected fractures, cell edema and more vacuoles. Compared with in the control group, levels of p-p38 and p-JNK in testicular tissue were significantly increased (P<0.05). In the control group and in low-, medium- and high-dose groups, the p-p38/p38 ratios were 1.35±0.13, 3.46±0.10, 5.71±0.26 and 4.79±0.21, respectively. The corresponding p-JNK/JNK ratios were 2.07±0.0, 4.77±0.18, 3.63±0.06 and 4.85±0.15. Claudin-11 levels were significantly lower (P<0.05) than control values in each dosed group. The corresponding values in control, low-dose, medium-dose and high-dose groups were 8.33±0.36, 2.06±0.27, 3.37±0.27 and 1.55±0.19, respectively.Conclusion:BDE-209 increased expression of proteins in the MAPK pathway and decreased expression of the BTB tight junction protein claudin-11 in testicular tissue. It also caused ultrastructural damage to the Sertoli cell BTB tight junctions. This suggested that BDE-209 might damage Sertoli cells BTB through effects on the MAPK pathway.
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Anhui Medical University, Hefei 230032, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: R X
authors.initials: RX
authors.lastname: Dai
authors.forename: D J
authors.initials: DJ
authors.lastname: Chen
authors.forename: C M
authors.initials: CM
authors.lastname: Wang
authors.forename: H F
authors.initials: HF
authors.lastname: Lin
authors.forename: Y R
authors.initials: YR
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Tang
authors.forename: J X
authors.initials: JX
authors.lastname: Zhai
mesh_terms: D000818:Animals; D001814:Blood-Testis Barrier / Q000187:drug effects*; D055768:Halogenated Diphenyl Ethers / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011494:Protein Kinases; D012708:Sertoli Cells / Q000187:drug effects; D013737:Testis / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D055768:Halogenated Diphenyl Ethers; D011494:Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C010902:decabromobiphenyl ether