Mesenchymal Stem Cells Restore Ovarian Function and Follicular Morphology Changes in Cyclophosphamide-Induced Infertility in Female Rats

Document Type : Original Article

Authors

1 Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Benha University, Egypt

2 Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Benha University, Egypt.

3 Department of Histology, Faculty of Veterinary Medicine, Benha University, Egypt.

4 Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Egypt.

5 Department of Pathology, Faculty of Medicine, Mansoura University, Egypt.

6 Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Egypt.

Abstract

Abstract
Premature ovarian failure (POF) contributes significantly to female infertility in young women. It mainly developed after chemotherapy medication, particularly with alkylating cytotoxic such as cyclophosphamide (CYP). The present research was designed to determine the advantages of mesenchymal stem cells (MSCs) as therapy for POF conditions in female rat models. For POF induction CYP (200mg/Kg b.wt) was injected intraperitoneally (i.p) followed by another activation dose of CYP (10mg/ b.wt, i.p) after one week. MSCs treatment enhanced by Bone Marrow-derived stem cells (BM-MSCs) or Umbilical Cord-derived stem cells (UC-MSCs) after two weeks of POF induction. The normal control (NC) group rats were injected with saline. The effects of POF modeling and MSCs (1 × 106 cells) transplantation through tail-vein were examined by sex hormonal analysis and morphological examination of ovarian follicles. CYP-induced rats POF show a significant reduction in AMH and E2 concentrations in addition to total, primordial, primary, secondary, and mature graffian follicles in contrast to the NC group (P<0.0001). FSH and LH concentrations were increased in the CYP group and degenerated follicles than in the NC group (P<0.0001). Transplanting MSCs improved the histopathological and hormonal analysis of the ovarian microenvironment induced by CYP (P<0.0001) with no significant difference in response to BM-MSCs or UC-MSCs. It was concluded that MSCs injection was a possible strategy for improving CYP-induced morphological changes, and sex-hormonal alterations, potentially promoting the restoration of CYP-induced infertility via POF.

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