Effect of cyclophosphamide on mouse oocyte in vitro fertilization and cleavage: recovery.

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.