The effects of Rosiglitazone on ovaries of female rats exposed to chemotherapy

Purpose: We aimed to show the effects of Rosiglitazone (which has anti-inflamator, angiogenic and immunosupressive effects) on the irreversible ovarian tissue damage of cyclophosphamide. Material and Method: Animal groups were designed as showed below: Control Group: No application was performed to this animals. (n=7)I. Group Chemotherapy Group: 100 mg/kg cyclophosphamide was applied by intraperitoneal injection. (n=7)II. Group Rosiglitazone Group: 100 mg/kg cyclophosphamide was applied by intraperitoneal injection. Three days before the chemotherapy; 3 mg/kg Rosiglitazone application begun and continiued fifteen consecutive days. Rosiglitazone was applied by orogastric sonda. (n=7)III. Group Chemotherapy + NaCl Group: 100 mg/kg cyclophosphamide was applied by intraperitoneal injection. Three days before the chemotherapy; 1 ml %0.9 NaCl solution application begun and continiued fifteen consecutive days. Rosiglitazone was applied by orogastric sonda. (n=7)At the end of the experiment, animals were sacrified under ether anesthesia. Ovary tissue slides were stained with Hematoxylene&Eosine (H&E) and Masson Trichrome for light microscopy. Immunohistochemical TUNEL stain (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling) was performed to determine apoptosis. The ovary tissues which were collected from the animals. RESULT:In control group; ovary tissue was normal. There were many primordial, primer, seconder, mature follicules and corpora lutea in the ovary cortex. And there was a small number of atretic follicules because of the normal ovarian cycle. Blood vessels and medulla was normal. In Group 1: Chemotherapy group, especially in growing follicules (primer and seconder) and mature follicules there were a widespread apoptosis and vacuolisation. There was cortical fibrosis in cortex and an increase in connective tissue around corpora lutea and mature follicules. There was an increase in atretic follicule numbers. In Group 2: Rosiglitazone group, there were many atretic follicules and apoptosis in growing follicules because of chemotherapy. But the incidances of apoptosis and atretic follicules were lower than Group 1 and 3. Cortical fibrosis and an increase of connective tissue was not seen in this group. In Group 3: Chemotherapy + NaCl group, the findings were similar with Group 1. There were many atretic follicules, widespread apoptosis in growing follicules, cortical fibrosis and increase of connective tissue around the mature follicules and corpora lutea. In TUNEL assay tissues showed widespread TUNEL positive cells even in control group. TUNEL positive cell numbers in control group was evaluated as the normal process of ovarian cycle. There was an increase of TUNEL positive cell counts in Group 1 and Group 3 but this increase was not statistically significant. The rate of TUNEL positive cell numbers was lower in Group 2 tha control group but the difference was not statistically significant. The differences between the Group 2 and Group 3 was found statisticallly significant. Primordial follicule number of control group was found significantly higher than Group 1, Group 2 and Group 3. Number of primordial follicules in Group 2 was found statistically higher than Group 1 and Group 3. There was no significant statistical difference between Group 1 and Group 3.Preantral follicule number of control group was found significantly higher than Group 1 and Group 3. There was no significant difference between Group 2 and Control. The difference between Group 1, Group 2 and Group 3 was not significant statistically. Preantral folicule number of Group 2 was significantly higher than Group 3. Antral follicule number of control group was significantly higher than Group 1 and Group 3. There was no significant difference between control and Group 2. There was not a statistically significancy between Group 1, Group 2 and Group 3. But antral follicule number of Group 2 was significantly higher than Group 3. There was no statistical significancy between corpora lutea numbers of the groups. CONCLUSION: In our study, we showed the fibrotic and apoptotic effect of cyclophosphamide by histologic and immunohistochemical techniques. According to our results; we consider that Rosiglitazone has a diminishing effect on apoptosis caused by cyclophosphamide. Also Rosiglitazone has a diminishing effect on primordial, preantral and antral folicule number reducing effect of cyclophosphamide. In our opinion, more studies are needed to understand the mechanism of Rosiglitazone in chemotherapy damage and if Rosiglitazone has a ability to protect primordial folicule reserve of ovary in chemotherapy. Keywords: Rosiglitazone, cyclophosphamide, apoptosis, ovary, primordial follicule.