title: Possible direct cytoxicity effects of cyclophosphamide on cultured human follicles: an electron microscopy study.
abstract: OBJECTIVE
  To evaluate the direct effect of cyclophosphamide on cultured human ovarian follicles.
  
  
  METHODS
  Human ovarian cortical slices from premenopausal women were incubated with medium containing cyclophosphamide (0.0005-0.5 mg/mL) for 2-48 h and assessed by transmission electron microscopy. Noncultured specimens and samples cultured without cyclophosphamide were used as controls.
  
  
  RESULTS
  There were significantly more damaged granulosa cell nuclei after incubation with 0.5 mg/mL cyclophosphamide for at least 4 h. There were also more changes in the basement membrane after incubation with cyclophosphamide at concentrations of 0.05 and 0.5 mg/mL.
  
  
  CONCLUSIONS
  Although the cyclophosphamide dose that caused damage to the granulosa cell nuclei was above the pharmacological level, our results suggest that cyclophosphamide, and not only its active metabolite phospharamide mustard, might have a destructive effect on human follicles, as it remains in the circulation longer. This effect could be mediated by damage to the granulosa cells and perhaps the basement membrane.
authors.affiliation: Department of Obstetrics and Gynecology, Rabin Medical Center, Petah Tikva, Israel.
authors.forename: Ahud
authors.initials: A
authors.lastname: Raz
authors.forename: Benjamin
authors.initials: B
authors.lastname: Fisch
authors.forename: Elimelech
authors.initials: E
authors.lastname: Okon
authors.forename: Dov
authors.initials: D
authors.lastname: Feldberg
authors.forename: Shmuel
authors.initials: S
authors.lastname: Nitke
authors.forename: Hila
authors.initials: H
authors.lastname: Raanani
authors.forename: Ronit
authors.initials: R
authors.lastname: Abir
mesh_terms: D000478:Alkylation; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006107:Granulosa Cells; D006801:Humans; D008854:Microscopy, Electron; D006080:Ovarian Follicle / Q000187:drug effects* / Q000648:ultrastructure
chemical_list: D003520:Cyclophosphamide