Evaluation of melfalan-induced premature ovarian failure in a rat model

Today's treatment practices have increased the long-term survival of young patients with cancer. However, modern chemotherapy regimens can cause ovarian damage and infertility, resulting in premature ovarian insufficiency (POI). The aim of this study is to evaluate the effects of melpalan treatment on the rat ovary at histopathological, immunohistochemical and biochemical levels. In this study 36 female Wistar rats were used. To create the POI model, rats were divided into two groups: control and POI groups. No application was made to the control group. A single dose of 5 mg/kg melphalan intraperitoneal injection was administered to create POI. Animals in the POI group were divided into four subgroups according to the time of sacrifice; Group A was sacrificed 24 hours after melphalan administration, Group B was sacrificed after four weeks, Group C was sacrificed after eight weeks, and Group D was sacrificed after 9 weeks. At the end of the study, the ovaries were used for histopathological and immunohistochemical studies. Serum AMH, FSH, E2 and PR hormone levels were measured. IL-1β, CRP, TNF-α, IL-6 and IFB were evaluated by immunohistochemical methods. BUN, CAT, GSH, MDA, SOD, CR, TAS, TOS and OSI values were measured in serum and tissue samples. In the ovaries of the melphalan-treated groups, there was damage and atresia in all follicles, and damage occurred in both oocytes and granulosa cells. Congestion, bleeding, leukocyte infiltration, interstitial edema, fibrosis and necrotic cells were detected. There was immunoreactivity for IL-6, IL-1β, CRP, TNF-α, and IFB in all groups administered melphalan. Melphalan caused an increase in FSH and LH levels and a decrease in AMH, E2 and prolactin levels. Melphalan caused changes in BUN, CAT, GSH, MDA, SOD, TAS, TOS, OSI values in both serum and tissue. These results show that POI developed in experimental animals with melphalan administration. Increase in fibrous tissue, vascular disorders, and changes in hormone values are compatible with histopathological findings. Melphalan contributes to the development of the inflammatory process in the ovaries. Changes were observed in antioxidant protein levels. In conclusion, melphalan caused the development of primordial ovarian failure in the rats.