Pydyn E F, Ataya K M
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan.
Reprod Toxicol. 1991;5(1):73-8. doi: 10.1016/0890-6238(91)90113-t.
To investigate the mechanism of cyclophosphamide (CTX)-induced ovarian failure, we previously reported that CTX metabolites added in vitro inhibit mouse oocyte fertilization and embryo development. In this study, we injected CTX (100 mg/kg) intraperitoneally in female mice at 0, 1, 4, 14, 18, and 24 h before sacrifice. Mice were superovulated with PMSG and hCG. Oocytes were recovered, washed, and fertilized with sperm obtained from nontreated proven breeders, and incubated for 3 days in 5% CO2 in air. CTX reduced oocyte fertilization and early cleavage rates. To examine the recovery process, CTX was injected at 0, 1, 3, 7, and 14 days before sacrifice. The most pronounced adverse effects on oocyte number and function were observed 1 and 3 days after exposure to CTX. Evidence of partial recovery was observed one week after CTX treatment. The data demonstrate that exposure of oocytes to CTX metabolites in vivo adversely effects oocyte function. This process, however, appears to be partially reversible. The oocytes may be involved in the mechanism of CTX-induced ovarian failure.
为了研究环磷酰胺（CTX）诱导卵巢功能衰竭的机制，我们之前报道过体外添加CTX代谢物可抑制小鼠卵母细胞受精和胚胎发育。在本研究中，我们在处死前0、1、4、14、18和24小时对雌性小鼠腹腔注射CTX（100 mg/kg）。用孕马血清促性腺激素（PMSG）和人绒毛膜促性腺激素（hCG）对小鼠进行超排卵处理。回收卵母细胞，洗涤后与未经处理的已证实有繁殖能力的雄鼠的精子受精，并在含5%二氧化碳的空气中孵育3天。CTX降低了卵母细胞受精率和早期分裂率。为了研究恢复过程，在处死前0、1、3、7和14天注射CTX。在接触CTX后1天和3天观察到对卵母细胞数量和功能最明显的不利影响。在CTX处理一周后观察到部分恢复的迹象。数据表明，体内卵母细胞暴露于CTX代谢物会对卵母细胞功能产生不利影响。然而，这一过程似乎部分是可逆的。卵母细胞可能参与了CTX诱导的卵巢功能衰竭的机制。
