title: Molecular alterations underlying the enhanced disruption of spermatogenesis by 2,5-hexanedione and carbendazim co-exposure.
abstract: The current study investigated the co-exposure effects of 2,5-hexanedione (HD) and carbendazim (CBZ) on gene expression underlying the enhanced pathology previously observed. Adult male rats were exposed to HD (0.33 or 1%) followed by CBZ (67 or 200 mg/kg), and testis samples were collected after 3 and 24 h. Microarray analysis at 3 h revealed that CBZ and HD interact in an agonistic, or synergistic, way at the gene level. Further analysis of candidate genes by qRT-PCR at both 3 and 24 h after co-exposure, revealed that Loxl1 and Clca2/Clca4l were both decreased in expression. Immunohistochemical analysis of Loxl1 at 24 h revealed that Loxl1 is localized to the seminiferous tubules, with the most intense staining in the basement membrane, blood vessels, and acrosomes, with the relative intensity reflecting the gene level changes at 3 h. These findings provide candidate genes for further investigation of the testicular response to damage.
authors.affiliation: Department of Pathology and Laboratory Medicine, Brown University, Providence, RI 02903, USA.
authors.forename: Sarah N
authors.initials: SN
authors.lastname: Campion
authors.forename: Natasha
authors.initials: N
authors.lastname: Catlin
authors.forename: E Andres
authors.initials: EA
authors.lastname: Houseman
authors.forename: Janan
authors.initials: J
authors.lastname: Hensley
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Sui
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Gaido
authors.forename: Zhijin
authors.initials: Z
authors.lastname: Wu
authors.forename: Kim
authors.initials: K
authors.lastname: Boekelheide
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000235:genetics; D000818:Animals; D001562:Benzimidazoles / Q000633:toxicity*; D002219:Carbamates / Q000633:toxicity*; D018118:Chloride Channels / Q000235:genetics; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006588:Hexanones / Q000633:toxicity*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D014404:Tubulin / Q000235:genetics
chemical_list: D001562:Benzimidazoles; C574515:CLCA2 protein, rat; D002219:Carbamates; D018118:Chloride Channels; D006588:Hexanones; D009419:Nerve Tissue Proteins; C120532:Shank3 protein, rat; C488416:Tubb3 protein, rat; D014404:Tubulin; C011269:2,5-hexanedione; D000594:Amino Acid Oxidoreductases; C574516:LOXL1 protein, rat; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C100151:dipeptidyl peptidase II; C006698:carbendazim