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Methylglyoxal-Dependent Glycative Stress and Deregulation of SIRT1 Functional Network in the Ovary of PCOS Mice.
Emidio, Giovanna Di; Placidi, Martina; Rea, Francesco; Rossi, Giulia; Falone, Stefano; Cristiano, Loredana; Nottola, Stefania; D'Alessandro, Anna Maria; Amicarelli, Fernanda; Palmerini, Maria Grazia; Tatone, Carla.
Afiliación
  • Emidio GD; Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
  • Placidi M; Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
  • Rea F; Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
  • Rossi G; Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
  • Falone S; Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
  • Cristiano L; Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
  • Nottola S; Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, 00161 Roma, Italy.
  • D'Alessandro AM; Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
  • Amicarelli F; Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
  • Palmerini MG; Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
  • Tatone C; Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
Cells ; 9(1)2020 01 14.
Article en En | MEDLINE | ID: mdl-31947651
Advanced glycation end-products (AGEs) are involved in the pathogenesis and consequences of polycystic ovary syndrome (PCOS), a complex metabolic disorder associated with female infertility. The most powerful AGE precursor is methylglyoxal (MG), a byproduct of glycolysis, that is detoxified by the glyoxalase system. By using a PCOS mouse model induced by administration of dehydroepiandrosterone (DHEA), we investigated whether MG-dependent glycative stress contributes to ovarian PCOS phenotype and explored changes in the Sirtuin 1 (SIRT1) functional network regulating mitochondrial functions and cell survival. In addition to anovulation and reduced oocyte quality, DHEA ovaries revealed altered collagen deposition, increased vascularization, lipid droplets accumulation and altered steroidogenesis. Here we observed increased intraovarian MG-AGE levels in association with enhanced expression of receptor for AGEs (RAGEs) and deregulation of the glyoxalase system, hallmarks of glycative stress. Moreover, DHEA mice exhibited enhanced ovarian expression of SIRT1 along with increased protein levels of SIRT3 and superoxide dismutase 2 (SOD2), and decreased peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC1α), mitochondrial transcriptional factor A (mtTFA) and translocase of outer mitochondrial membrane 20 (TOMM20). Finally, the presence of autophagy protein markers and increased AMP-activated protein kinase (AMPK) suggested the involvement of SIRT1/AMPK axis in autophagy activation. Overall, present findings demonstrate that MG-dependent glycative stress is involved in ovarian dysfunctions associated to PCOS and support the hypothesis of a SIRT1-dependent adaptive response.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ovario / Síndrome del Ovario Poliquístico / Piruvaldehído / Productos Finales de Glicación Avanzada / Sirtuina 1 Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cells Año: 2020 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ovario / Síndrome del Ovario Poliquístico / Piruvaldehído / Productos Finales de Glicación Avanzada / Sirtuina 1 Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Cells Año: 2020 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza