7,12-dimetilbenz(a)antrasen (DMBA) ile indüklenen fare ovaryumunda hippo sinyal yolağının belirlenmesi

7,12-dimethylbenz(a)anthracene (DMBA) has well known ovotoxicant and present carcinogenic effects on ovarian follicular development in rodents. The Hippo signaling pathway induces cell proliferation, differentiation, apoptosis and regulation of organ size in diverse species. The relationship between follicular development and the Hippo signaling pathway in DMBA-induced mouse ovaries has not been investigated in previous studies. Therefore, in this thesis study, we hypothesized that Hippo signaling pathway proteins may have a role in the ovotoxicity which is induced by DMBA treatment in the mouse ovary. We aimed to demonstrate the Hippo signaling pathway in DMBA-treated ovaries by immunohistochemistry and quantitative real-time PCR (qRT-PCR). In this thesis study, 28 days old 18 BalbC female mice were used and designed 3 groups (n=6): Control (No treatment), Vehicle group (Daily injection of sesame oil), Experimental group (The intraperitoneal injection of DMBA (1 mg/kg in sesame oil) for 14 consecutive days). To demonstrate the morphological difference between DMBA and control group mouse ovary, sections were stained with Periodic-Acid Schiff (PAS) staining. AMH serum levels analyzed by ELISA and follicles were counted to evaluate follicle reserve. Immunohistochemistry was performed in the ovary to determine the localization of Hippo signaling pathway proteins MST1/2, LATS1/2, YAP1, TEAD4 and to show oxidative stress with NTY antibody. The levels of Hippo signaling proteins at the mRNA level were measured by qRT-PCR. According to the results, DMBA-treated ovaries showed decreased follicular reserve, increased oxidative stress and follicular atresia. In our study, we provide evidence for the first time of the relationship between follicular development and the Hippo signaling pathway in DMBA-treated mouse ovaries. We believe that our data will shed new light on the rapid depletion of follicular reserve and the signaling mechanism related to DMBA-induced ovotoxicity on mouse ovaries. Therefore, it is suggested that our results may contribute to the further investigation of ovotoxicity related problems and the development of new strategies.