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Protective effects of a SIRT1 inhibitor on primordial follicle activation and growth induced by cyclophosphamide: insights from a bovine in vitro folliculogenesis system.
Di Emidio, Giovanna; Tatone, Carla; Barbato, Vincenza; Genovese, Vincenzo; Placidi, Martina; Talevi, Riccardo; Gualtieri, Roberto.
Afiliación
  • Di Emidio G; Department of Life, Health and Environmental Sciences, University of L'Aquila, Building Delta 6, Via G. Petrini 6, 67100, L'Aquila, Italy.
  • Tatone C; Department of Life, Health and Environmental Sciences, University of L'Aquila, Building Delta 6, Via G. Petrini 6, 67100, L'Aquila, Italy. carla.tatone@univaq.it.
  • Barbato V; Dipartimento di Biologia, Università di Napoli "Federico II", Complesso Universitario di Monte S Angelo, Via Cinthia, 80126, Naples, Italy.
  • Genovese V; Dipartimento di Biologia, Università di Napoli "Federico II", Complesso Universitario di Monte S Angelo, Via Cinthia, 80126, Naples, Italy.
  • Placidi M; Department of Life, Health and Environmental Sciences, University of L'Aquila, Building Delta 6, Via G. Petrini 6, 67100, L'Aquila, Italy.
  • Talevi R; Dipartimento di Biologia, Università di Napoli "Federico II", Complesso Universitario di Monte S Angelo, Via Cinthia, 80126, Naples, Italy.
  • Gualtieri R; Dipartimento di Biologia, Università di Napoli "Federico II", Complesso Universitario di Monte S Angelo, Via Cinthia, 80126, Naples, Italy.
J Assist Reprod Genet ; 39(4): 933-943, 2022 Apr.
Article en En | MEDLINE | ID: mdl-35247119
PURPOSE: Although oncological advances have improved survival rates of female cancer patients, they often suffer a reduced fertility due to treatment side effects. In the present study, we evaluated the potential fertoprotective effects of the specific inhibitor of SIRT1, EX-527, on the gonadotoxic action exerted by cyclophosphamide (CPM) on loss of primordial follicles (PFs). METHODS: The effects of the CPM metabolite phosphoramide mustard (PM) on follicle activation, growth and viability and the protective action of EX-527 against PM effects were evaluated on bovine ovarian cortical strips in vitro cultured for 1 or 6 days. To understand whether PFs exposed to PM plus EX-527 were able to activate and grow to the secondary stage after suspension of the treatment, strips cultured for 3 days in PM plus EX-527 for 3 days were transferred to plain medium until day 6. Follicle growth and health were evaluated through histology and viability assay at a confocal microscope. In order to investigate the molecular pathways underlying the ovarian response to PM in the presence of EX-527, we analysed the protein level of SIRT1, HuR, PARP1 and SOD2 after 1 day of in vitro culture. RESULTS: We found that (1) PM, the main CPM active metabolite, promotes PF activation; (2) the ovarian stress response induced by PM includes a SIRT1-dependent pathway; and (3) EX-527 reduces PF activation and growth induced by PM. CONCLUSION: SIRT1 can represent a candidate molecule to be targeted to protect ovarian follicles from alkylating agents and EX-527 could represent a potential fertoprotective agent for cancer patients.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sirtuina 1 / Folículo Ovárico Límite: Animals Idioma: En Revista: J Assist Reprod Genet Asunto de la revista: GENETICA / MEDICINA REPRODUTIVA Año: 2022 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Sirtuina 1 / Folículo Ovárico Límite: Animals Idioma: En Revista: J Assist Reprod Genet Asunto de la revista: GENETICA / MEDICINA REPRODUTIVA Año: 2022 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Países Bajos