Mesenchymal stem cells promote the repair of chemotherapy-induced premature ovarian failure in female rats

Abstract

Keywords Chemotherapeutic drugs, particularly alkylating cytotoxics such as cyclophosphamide (CYP) play a great job in inducing premature ovarian failure (POF). Hormone replacement therapy (HRT) is a widely used medication to improve hormone secretion. However, long-term HRT increases the risk of breast cancer and cardiovascular disease is concerning. Therefore, there is an urgent need to develop a safe and effective treatment for POF. Bone Marrow-(BM-MSCs) and Umbilical Cord -(UC-MSCs) derived stem cells (SCs) were isolated and identified from healthy rats. For POF induction, CYP (200mg/Kg b.wt) injected (i.p) into CYP, CYP+BMSCs, and CYP+UCMSCs followed by another dose (10mg/ b.wt, i.p) after one week. The normal control (NC) group were injected with saline. After two weeks of POF induction MSCs (1 × 10 6 cells/ml) of media were transplanted into POF rats through tail-vein. The effects of MSCs transplantation to POF were evaluated through sex hormones, iron, and complete blood count (CBC) analysis. POF-induced rats showed a significant increase in serum FSH and LH, with marked decrease in anti-Mullerian hormone (AMH) and estradiol (E2). Obvious increase in serum iron level observed in CYP group compared to the NC. Moreover, POF-induced rats displayed leucopenia, erythrocytopenia, and thrombocytopenia with a significant reduction in Hb, PCV, MCV, MCH, and MCHC compared to the NC. Administration of MSCs to CYP-injured rats significantly improved female reproductive hormones disturbances, iron, and hemogram. It was suggested that MSCs was a potential approach for improving sex hormones, iron, and hematological alterations, and potentially promoting the restoration of CYP-induced POF. Cyclophosphamide