title: Sub-lethal concentrations of CdCl2 disrupt cell migration and cytoskeletal proteins in cultured mouse TM4 Sertoli cells.
abstract: The aims of this study were to examine the effects of CdCl2 on the viability, migration and cytoskeleton of cultured mouse TM4 Sertoli cells. Time- and concentration-dependent changes were exhibited by the cells but 1 μM CdCl2 was sub-cytotoxic at all time-points. Exposure to 1 and 12 μM CdCl2 for 4 h resulted in disruption of the leading edge, as determined by chemical staining. Cell migration was inhibited by both 1 and 12 μM CdCl2 in a scratch assay monitored by live cell imaging, although exposure to the higher concentration was associated with cell death. Western blotting and immunofluorescence staining indicated that CdCl2 caused a concentration dependent reduction in actin and tubulin levels. Exposure to Cd(2+) also resulted in significant changes in the levels and/or phosphorylation status of the microtubule and microfilament destabilising proteins cofilin and stathmin, suggesting disruption of cytoskeletal dynamics. Given that 1-12 μM Cd(2+) is attainable in vivo, our findings are consistent with the possibility that Cd(2+) induced impairment of testicular development and reproductive health may involve a combination of reduced Sertoli cell migration and impaired Sertoli cell viability depending on the timing, level and duration of exposure.
authors.affiliation: School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, United Kingdom. Electronic address: biola.egbowon@ntu.ac.uk.
authors.forename: Biola F
authors.initials: BF
authors.lastname: Egbowon
authors.affiliation: School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, United Kingdom.
authors.forename: Wayne
authors.initials: W
authors.lastname: Harris
authors.affiliation: School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, United Kingdom.
authors.forename: Gordon
authors.initials: G
authors.lastname: Arnott
authors.affiliation: School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, United Kingdom.
authors.forename: Chris Lloyd
authors.initials: CL
authors.lastname: Mills
authors.affiliation: School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, United Kingdom. Electronic address: alan.hargreaves@ntu.ac.uk.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Hargreaves
mesh_terms: D000818:Animals; D019256:Cadmium Chloride / Q000633:toxicity*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D012708:Sertoli Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
chemical_list: D003598:Cytoskeletal Proteins; D019256:Cadmium Chloride
keywords: Cadmium chloride; Cell migration; Cytoskeleton; Reproductive toxicity; Sertoli cells; Testicular development