Effect of "activated" cyclophosphamide on mouse oocyte in vitro fertilization and cleavage.
To investigate the involvement of oocytes in the mechanism of chemotherapy-induced ovarian failure, ovulation was induced in mice using pregnant mares' serum gonadotropin and human chorionic gonadotropin. Oocytes (with cumulus) were incubated for 4 hours with "activated" cyclophosphamide, 4-hydroperoxycyclophosphamide (PCTX) at 0, 1, 10, 100, and 500 micrograms/mL. Oocytes were then washed, fertilized with sperm obtained from nontreated male proven breeders, and incubated for 4 days. "Activated" cyclophosphamide inhibited dissolution of the cumulus and reduced fertilization and early cleavage rates in a dose-related manner. The data demonstrate that exposure of oocytes to cyclophosphamide metabolites in vitro adversely affects oocyte function. Oocytes may be involved in the mechanism of cyclophosphamide-induced ovarian failure.
Ataya
K M
KM
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Pydyn
E F
EF
Sacco
A G
AG
D000818:Animals; D002970:Cleavage Stage, Ovum / Q000187:drug effects*; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro / Q000187:drug effects*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009865:Oocytes / Q000187:drug effects*
D003520:Cyclophosphamide; D003577:Cytochrome P-450 Enzyme System; C011272:perfosfamide