Possible direct cytoxicity effects of cyclophosphamide on cultured human follicles: An electron microscopy study

Ahud Raz, Benjamin Fisch, Elimelech Okon, Dov Feldberg, Shmuel Nitke, Hila Raanani, Ronit Abir*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: 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.

Original languageEnglish
Pages (from-to)500-506
Number of pages7
JournalJournal of Assisted Reproduction and Genetics
Volume19
Issue number10
DOIs
StatePublished - 1 Oct 2002
Externally publishedYes

Funding

FundersFunder number
AhR
Rabin Medical Center
Steering Committee for Research Promotion

    Keywords

    • Cyclophosphamide
    • Granulosa cells
    • Oocytes
    • Ovarian failure
    • Primordial follicles

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