Raz Ahud, Fisch Benjamin, Okon Elimelech, Feldberg Dov, Nitke Shmuel, Raanani Hila, Abir Ronit
Department of Obstetrics and Gynecology, Rabin Medical Center, Petah Tikva, Israel.
J Assist Reprod Genet. 2002 Oct;19(10):500-6. doi: 10.1023/a:1020318704960.
To evaluate the direct effect of cyclophosphamide on cultured human ovarian follicles.
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.
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.
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.
评估环磷酰胺对培养的人卵巢卵泡的直接作用。
将绝经前妇女的人卵巢皮质切片与含环磷酰胺（0.0005 - 0.5毫克/毫升）的培养基孵育2 - 48小时，并用透射电子显微镜进行评估。未培养的标本和未用环磷酰胺培养的样本用作对照。
用0.5毫克/毫升环磷酰胺孵育至少4小时后，受损颗粒细胞核显著增多。用0.05和0.5毫克/毫升浓度的环磷酰胺孵育后，基底膜的变化也更多。
尽管导致颗粒细胞核损伤的环磷酰胺剂量高于药理水平，但我们的结果表明，环磷酰胺不仅是其活性代谢产物磷酰胺氮芥，可能对人卵泡具有破坏作用，因为它在循环中停留的时间更长。这种作用可能是由颗粒细胞和可能的基底膜损伤介导的。
