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Mol Biol Rep ; 48(1): 363-370, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33319323

RESUMO

Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disease caused by a mutation in the IDUA gene, which codes α-L-iduronidase (IDUA), a lysosomal hydrolase that degrades two glycosaminoglycans (GAGs): heparan sulfate (HS) and dermatan sulfate (DS). GAGs are macromolecules found mainly in the extracellular matrix and have important signaling and structural roles which are essential to the maintenance of cell and tissue physiology. Nondegraded GAGs accumulate in various cell types, which characterizes MPS I as a multisystemic progressive disease. Many tissues and vital organs have been described in MPS I models, but there is a lack of studies focused on their effects on the reproductive tract. Our previous studies indicated lower sperm production and morphological damage in the epididymis and accessory glands in male MPS I mice, despite their ability to copulate and to impregnate females. Our aim was to improve the testicular characterization of the MPS I model, with a specific focus on ultrastructural observation of the different cell types that compose the seminiferous tubules and interstitium. We investigated the testicular morphology of 6-month-old male C57BL/6 wild-type (Idua+/+) and MPS I (Idua-/-) mice. We found vacuolated cells widely present in the interstitium and important signs of damage in myoid, Sertoli and Leydig cells. In the cytoplasmic region of Sertoli cells, we found an increased number of vesicles with substrates under digestion and a decreased number of electron-dense vesicles similar to lysosomes, suggesting an impaired flux of substrate degradation. Conclusions: Idua exerts an important role in the morphological maintenance of the seminiferous tubules and the testicular interstitium, which may influence the quality of spermatogenesis, having a greater effect with the progression of the disease.


Assuntos
Glicosaminoglicanos/genética , Doenças por Armazenamento dos Lisossomos/genética , Mucopolissacaridose I/genética , Células de Sertoli/patologia , Animais , Modelos Animais de Doenças , Progressão da Doença , Humanos , Células Intersticiais de Cajal/metabolismo , Células Intersticiais de Cajal/patologia , Células Intersticiais do Testículo/metabolismo , Células Intersticiais do Testículo/patologia , Doenças por Armazenamento dos Lisossomos/metabolismo , Doenças por Armazenamento dos Lisossomos/patologia , Masculino , Camundongos , Mucopolissacaridose I/metabolismo , Mucopolissacaridose I/patologia , Mutação/genética , Células de Sertoli/metabolismo , Espermatozoides/metabolismo , Espermatozoides/patologia
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