2-hydroxyoestradiol and 2-methoxyoestradiol, two endogenous oestradiol metabolites, induce DNA fragmentation in Sertoli cellsReportar como inadecuado




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Resumen

Elevated intratesticular levels of hydroxyoestradiols and methoxyoestradiols,two classes of endogenous oestradiol metabolites, have been associated withmale infertility. The aim of this study was to explore the effects of 2-hydroxyoestradiol2OHE2, 4-hydroxyoestradiol 4OHE2, 2-methoxyoestradiol2ME2 and 4-methoxyoestradiol 4ME2 on Sertoli cell viability. For this,TM4 cells were incubated with different concentrations of these metabolites for24 h to then evaluate the viability and DNA integrity by MTS and TUNELassay respectively. The participation of classical oestrogen receptors and theinvolvement of oxidative stress and apoptotic mechanisms were also evaluatedco-incubating TM4 cells with these estradiol metabolites and with the drugsICI182780, N-acetylcysteine and Z-VAD-FMK respectively. Only high concentrationsof 2OHE2 and 2ME2 decreased cell viability inducing DNA fragmentation.In addition, ICI182780 did not block the effect of 2OHE2 and 2ME2,while N-Acetylcysteine and Z-VAD-FMK only blocked the effect of 2OHE2.Moreover, 2OHE2 but not 2ME2 induced PARP and caspase-3 cleavage. Finally,lower 2OHE2 and 2ME2 concentrations 0.01–0.1–1.0 lmol l 1 decreased Sertolicell viability 48 h post-treatment. Our results support the hypothesis thatelevated intratesticular 2OHE2 or 2ME2 concentrations could be related to maleinfertility since 2OHE2 by apoptosis and 2ME2 by undetermined mechanismsinduce DNA fragmentation in Sertoli cells.



Autor: Valencia Mandiola, Camila; - Molina, C.; - Florez, M.; - Buñay, J.; - Moreno, R. D.; - Orihuela, P. A.; - Castro Lara, Ariel; -

Fuente: http://repositorio.uchile.cl/



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