Propylthiouracil-induced congenital hypothyroidism upregulates vimentin phosphorylation and depletes antioxidant defenses in immature rat testis.
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.
Zamoner
Ariane
A
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, CEP 90035-003, RS, Brazil.
Barreto
Kátia Padilha
KP
Filho
Danilo Wilhelm
DW
Sell
Fabíola
F
Woehl
Viviane Mara
VM
Guma
Fátima Costa Rodrigues
FC
Pessoa-Pureur
Regina
R
Silva
Fátima Regina Mena Barreto
FR
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
D000975:Antioxidants; D017382:Reactive Oxygen Species; D014746:Vimentin; D011441:Propylthiouracil; D048051:p38 Mitogen-Activated Protein Kinases