THE RESEARCH OF TLR4 INVOLVEMENT IN SIGNALING PATHWAYS ACTIVATED IN MURINE OVARIAN CELLS UNDER THE INFLUENCE OF LIPOPOLYSACCHARIDE

Abstract

Toll-like receptor 4 (TLR4) is a widely described transmembrane protein involved in the inflammatory process. Bacterial infection is one of the main factors influencing the change in TLR4 expression. At the same time, the level of TLR4 expression directly correlates with the severity of the process, which in some cases allows considering these receptors as an early markers of infection. Early it was shown disruption of ovarian cell functions under the condi-tions of experimental endotoxemia in mice. Pathological changes of follicular environment of oocytes resulted in impairment of oocyte meiotic maturation. However, involvement of TLR4 in activation of signaling pathways in ovar-ian cells under the influence of lipopolysaccharide (LPS), requires careful study. In the present work we have investi-gated pharmacological effect of TAK242 (inhibitor of TLR4) on oocyte meiotic maturation in vitro under the influ-ence of LPS. The study was done on cumulus oocyte complexes (COCs) and oocytes, denuded from cumulus cells, which were isolated from ovaries of Albino mice. It was shown that LPS inhibited meiotic maturation in vitro of COCs and cumulus-denuded oocytes. However, 15 min pretreatment with TLR4 inhibitor (ТАК242) with the subsequent ad-dition of LPS to the culture medium, improved meiotic maturation of both COCs and cumulus-denuded oocytes. More-over, simultaneous exposure to ТАК242 and LPS did not show any significant differences in meiotic maturation of both COCs and cumulus-denuded oocytes compared with 15 min pretreatment with ТАК242. The results obtained may indicate the presence of TLR4 on murine oocytes and cumulus cells. Also the results can serve as the basis for the re-search of feasibility of therapeutic use of TLR4 inhibitors in diseases in the course of which interaction between TLR4 and its ligands (in particular LPS) occur.