title: Ex-vivo assessment of chronic toxicity of low levels of cadmium on testicular meiotic cells.
abstract: Using a validated model of culture of rat seminiferous tubules, we assessed the effects of 0.1, 1 and 10 μg/L cadmium (Cd) on spermatogenic cells over a 2-week culture period. With concentrations of 1 and 10 μg/L in the culture medium, the Cd concentration in the cells, determined by ICP-MS, increased with concentration in the medium and the day of culture. Flow cytometric analysis enabled us to evaluate changes in the number of Sertoli cells and germ cells during the culture period. The number of Sertoli cells did not appear to be affected by Cd. By contrast, spermatogonia and meiotic cells were decreased by 1 and 10 μg/L Cd in a time and dose dependent manner. Stage distribution of the meiotic prophase I and qualitative study of the synaptonemal complexes (SC) at the pachytene stage were performed by immunocytochemistry with an anti SCP3 antibody. Cd caused a time-and-dose-dependent increase of total abnormalities, of fragmented SC and of asynapsis from concentration of 0.1 μg/L. Additionally, we observed a new SC abnormality, the "motheaten" SC. This abnormality is frequently associated with asynapsis and SC widening which increased with both the Cd concentration and the duration of exposure. This abnormality suggests that Cd disrupts the structure and function of proteins involved in pairing and/or meiotic recombination. These results show that Cd induces dose-and-time-dependent alterations of the meiotic process of spermatogenesis ex-vivo, and that the lowest metal concentration, which induces an adverse effect, may vary with the cell parameter studied.
authors.affiliation: Aix-Marseille Univ, UMR CNRS IMBE 7263, FR 3098 ECCOREV, 13005, Marseille, France.
authors.forename: Cendrine
authors.initials: C
authors.lastname: Geoffroy-Siraudin
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Perrard
authors.forename: Rahma
authors.initials: R
authors.lastname: Ghalamoun-Slaimi
authors.forename: Sazan
authors.initials: S
authors.lastname: Ali
authors.forename: Florence
authors.initials: F
authors.lastname: Chaspoul
authors.forename: André
authors.initials: A
authors.lastname: Lanteaume
authors.forename: Vincent
authors.initials: V
authors.lastname: Achard
authors.forename: Philippe
authors.initials: P
authors.lastname: Gallice
authors.forename: Philippe
authors.initials: P
authors.lastname: Durand
authors.forename: Marie-Roberte
authors.initials: MR
authors.lastname: Guichaoua
mesh_terms: D000818:Animals; D002104:Cadmium / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D008297:Male; D008540:Meiosis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects; D013737:Testis / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*
chemical_list: D002104:Cadmium