title: Postnatal exposure to low-dose decabromodiphenyl ether adversely affects mouse testes by increasing thyrosine phosphorylation level of cortactin.
abstract: Decabromodiphenyl ether (decaBDE) is a brominated flame retardant used in many commercial products such as televisions, computers, and textiles. Recent reports indicate that decaBDE adversely affects male reproductive organs in mice, but the underlying molecular mechanisms remain unknown. We hypothesized that decaBDE affects mouse testes by altering the expression and phosphorylation level of cortactin (CTTN), an F-actin-binding protein that is similar to flutamide, and we performed western blot analyses on testicular samples from mice subcutaneously injected with decaBDE (0.025, 0.25, and 2.5 mg/kg body weight/day) on postnatal days 1 to 5. Mice treated with low-dose decaBDE (0.025 mg/kg) showed reduced testicular weight, sperm count, elongated spermatid and Sertoli cell numbers, as well as induced Tyr phosphorylation of CTTN and reduced the expression level of p60 Src tyrosine kinase (SRC). Further, 0.25 and 2.5 mg/kg decaBDE-exposed groups produced an decrease the expression level of CTTN. High-dose decaBDE (2.5 mg/kg) showed increased abnormal germ cells, as well as induced Ser phosphorylation of CTTN and activated extracellular signal-regulated kinase (ERK1/2); however, high-dose decaBDE did not affect testicular weight and sperm count. These findings suggest that postnatal exposure to low-dose decaBDE inhibits mouse testicular development by increasing Tyr phosphorylation of CTTN, although different mechanisms may be involved depending on the dose of decaBDE.
authors.affiliation: Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chuo-ku, Chiba-Shi, Chiba, Japan.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Miyaso
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakamura
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Matsuno
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kawashiro
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Komiyama
authors.forename: Chisato
authors.initials: C
authors.lastname: Mori
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051356:Cortactin / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005411:Flame Retardants / Q000633:toxicity*; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D013076:Sperm Count; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D051356:Cortactin; C495869:Cttn protein, mouse; D005411:Flame Retardants; D055768:Halogenated Diphenyl Ethers; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C010902:decabromobiphenyl ether