The Effect of Sirtuin 1 Inhibitor Ex-527 and Activator Resveratrol on the Oocytes’ Cells Viability in Mice Model of Experimental Systemic Autoimmune Damage

Abstract

Introduction: Female infertility is a very common pathology for women of reproductive age with autoimmune disorders, which are known to be followed by the abnormal increment of reactive oxygen species levels, moreover, further contributing to follicular atresia and aging of oocytes in the ovaries what directly leads to infertility. Thus, in search for strategies of preventing oxidative threat to ovaries, the current study was aimed to assess the influence of sirtuin 1, a key cellular metabolism regulator and oxidative stress, activator/blocker on the viability of the follicular environment of oocytes (FEO) cells under conditions of experimental systemic autoimmune damage (ESAD). Methods: The study was performed using the model of ESAD on female mice. The FEO cells were cultivated in different conditions: resveratrol 20 µM, Ex-527 20 µM. After 24h, the cells were examined for viability; the ways of cell death via apoptosis, necrosis were estimated using the method of in vivo dual-color with fluorescent nucleic acid dyes Hoechst 33342 and propidium iodide, and the levels of autophagy were estimated using the autophagic vacuoles labeling with monodansylcadaverine assay. Results: The obtained data indicate that a specific inhibitor of sirtuin 1 Ex-527 (20 µM) in vitro inhibits the viability of cells of the FEO cells and increases the percent of cell death via autophagy, apoptosis, and necrosis. On the contrary, the activator of sirtuin 1 - resveratrol, led to an improvement of the viability status of FEO cells, while reducing the negative impact of the inflammatory process. Unidirectional action of Ex-527 and resveratrol compounds at the cellular level has been established. Conclusion: Thus, the results of the present study suggest the involvement of sirtuin 1 in the regulation of the damaging effect of reactive oxygen species on female ovarian cells under the conditions of experimental systemic autoimmune damage.