Stupchuk M. The effect of Sirtuins activity modulators and silver nanoparticles on the functional status of mouse ovarian cells

In the dissertation, according to a stated goal, a theoretical generalization is given and a new solution to the scientific problem concerning the involment of Sirtuins and nanomaterials in oogenesis under various experimental conditions is presented. The parameters of oocytes’ meiotic maturation and viability of cells of their follicular environment were investigated, as well as features of distribution of DNA single-strand breaks in cells of follicular environment of oocytes (FEO), which have not been studied previously, were assesed using the model of experimental systemic autoimmune damage (ESAD) and modeling of oxidative stress in vitro. The effect of Sirtuins activity modulators (resveratrol and nicotinamide), an inhibitor of NF-κB (BAY11-7082) and an inhibitor of mitochondrial carrier (PPT) under above mentioned experimental conditions was studied. It has been shown that the sirtuins inhibitor nicotinamide changes the parameters of vitality of FEO cells due to its effect on mitochondria; in conditions of oxidative stress in vitro, the transcription factor of NF-κB is involved in the mechanism of resveratrols impact on the process of oocyte meiotic maturation and vitality of FEO cells.Moreover, our data indicates that in the conditions of ESAD there is: a depression of meiotic maturation of oocytes at the stage of metaphase I and metaphase II; an increasement in the number of FEO cells with morphological signs of apoptosis and necrosis; an occurance of changes in the levels of expression of COX2, Grem1, and HAS2 genes in FEO cells; an increasement in the level of DNA primary damages to of the FEO cells. The injection of silver nanoparticles substance was not found to affect the process of oocytes meiotic maturation and cell death of the FEO cells, whereas in the conditions of ESAD the injection of silver nanoparticles was found to lead to the decreasement in the FEO cells DNA primary damages; it was also shown the increasement in the number of oocytes that restore meiotic maturation and form the first polar body in vitro, as well as the increasement of the number of living FEO cells and decreasement of the number of those cells with morphological signs of apoptotic death.