title: Mechanistic action of mesenchymal stem cell injection in the treatment of chemically induced ovarian failure in rabbits.
abstract: BACKGROUND
  No curative treatment is known for primary ovarian failure; however, mesenchymal stem cells (MSCs), through self-renewal and regeneration, push the trial to evaluate their role in the treatment of ovarian failure. The aim of this study was to explore the impact of MSCs on cyclophosphamide (CTX)-induced ovarian failure in rabbits and to clarify the mechanism(s) by which MSCs exert their action.
  
  
  METHODS
  Thirty-five adult female rabbits were injected with CTX to induce ovarian failure. Five rabbits were euthanized after the last injection of CTX for histological examination. The others (30 rabbits) were further subdivided into two groups: group 1 (ovarian failure group, 15 rabbits) received no treatment; group 2 (ovarian failure and MSC recipient group, 15 rabbits) received MSCs isolated from extracted bone marrow of male rabbits.
  
  
  RESULTS
  A decrease of follicle-stimulating hormone and an increase of estrogen and vascular endothelial growth factor (VEGF) levels in the MSC recipient group versus the ovarian failure group were found. Weak caspase-3 expression and +ve proliferating cell nuclear antigen staining after MSC injection were detected. Cytological and histological examinations showed increased follicle numbers with apparent normal structure of ovarian follicles in the MSC recipient group. Moreover, Y chromosome-containing cells from male donors were present within the ovarian tissues in group 2.
  
  
  CONCLUSIONS
  The current study suggests that intravenous injection of MSCs into rabbits with chemotherapy-induced ovarian damage improved ovarian function. MSCs accomplish this function by direct differentiation into specific cellular phenotypes and by secretion of VEGF, which influence the regeneration of the ovary.
authors.affiliation: Medical Biochemistry Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt. dr.somiahassan@yahoo.com
authors.forename: Somia H
authors.initials: SH
authors.lastname: Abd-Allah
authors.forename: Sally M
authors.initials: SM
authors.lastname: Shalaby
authors.forename: Heba F
authors.initials: HF
authors.lastname: Pasha
authors.forename: Amal S
authors.initials: AS
authors.lastname: El-Shal
authors.forename: Nermin
authors.initials: N
authors.lastname: Raafat
authors.forename: Sheren M
authors.initials: SM
authors.lastname: Shabrawy
authors.forename: Hanan A
authors.initials: HA
authors.lastname: Awad
authors.forename: Mona G
authors.initials: MG
authors.lastname: Amer
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Gharib
authors.forename: Eman A
authors.initials: EA
authors.lastname: El Gendy
authors.forename: Amal A
authors.initials: AA
authors.lastname: Raslan
authors.forename: Hassan M
authors.initials: HM
authors.lastname: El-Kelawy
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000633:toxicity*; D005260:Female; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced* / Q000378:metabolism / Q000628:therapy*; D011817:Rabbits; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D003520:Cyclophosphamide; D053148:Caspase 3