title: Propylthiouracil-induced congenital hypothyroidism upregulates vimentin phosphorylation and depletes antioxidant defenses in immature rat testis.
abstract: Congenital hypothyroidism was induced in rats by adding 0.05% 6-propyl-2-thiouracil in the drinking water from day 9 of gestation, and continually up to postnatal day 15. Structural alterations observed by light microscopy of seminiferous tubules and by transmission electron microscopy of Sertoli cells of treated animals were consistent with hypothyroid condition. Hypothyroidism was also associated with high phospho-p38 mitogen-activated protein kinase and decreased phospho-extracellular signal-regulated kinase 1/2 levels. Furthermore, the phosphorylation and the immunoreactivity of cytoskeletal-associated vimentin were increased without altering vimentin expression, suggesting an accumulation of insoluble and phosphorylated vimentin. These alterations in intermediate filament dynamics could result in loss of Sertoli cell cytoskeletal integrity and be somewhat related to the deleterious effects of hypothyroidism in testis. In addition, the mitochondrial alterations observed could also be related to defective cytoskeletal dynamics implying in cell damage. Moreover, we observed decreased oxygen consumption and unaltered lipid peroxidation in hypothyroid testis. However, we demonstrated decreased enzymatic and non-enzymatic antioxidant defenses, supporting an increased mitochondrial reactive oxygen species (ROS) generation, contributing to biochemical changes in hypothyroid testis. In addition, the changes in the testis histoarchitecture could be ascribed to cytoskeletal alterations, decreased antioxidant defenses, and increased ROS generation, leading to oxidative stress in the organ.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, CEP 90035-003, RS, Brazil.
authors.forename: Ariane
authors.initials: A
authors.lastname: Zamoner
authors.forename: Kátia Padilha
authors.initials: KP
authors.lastname: Barreto
authors.forename: Danilo Wilhelm
authors.initials: DW
authors.lastname: Filho
authors.forename: Fabíola
authors.initials: F
authors.lastname: Sell
authors.forename: Viviane Mara
authors.initials: VM
authors.lastname: Woehl
authors.forename: Fátima Costa Rodrigues
authors.initials: FC
authors.lastname: Guma
authors.forename: Regina
authors.initials: R
authors.lastname: Pessoa-Pureur
authors.forename: Fátima Regina Mena Barreto
authors.initials: FR
authors.lastname: Silva
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D003409:Congenital Hypothyroidism / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D003599:Cytoskeleton / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010101:Oxygen Consumption; D010766:Phosphorylation; D011441:Propylthiouracil; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012671:Seminiferous Tubules / Q000378:metabolism / Q000473:pathology; D012708:Sertoli Cells / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000378:metabolism* / Q000473:pathology; D014746:Vimentin / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D014746:Vimentin; D011441:Propylthiouracil; D048051:p38 Mitogen-Activated Protein Kinases