The incidence of cytoplasmic fragmentation in mouse embryos in vitro is not affected by inhibition of caspase activity

Objective: To investigate the relationship between cytoplasmic fragmentation and caspase activity in the mouse embryo. Design: Experimental laboratory study. Setting: University gynacology unit. Animal(s): One-cell zygote of mouse (MF1 X BALB/c). Intervention(s): Mouse embryos were treated with caspase inhibitors: benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (z-VAD-fmk) and benzyloxycarbonyl-Asp-glu-Val-Asp-fluoromethyl ketone (Z-DEVD-fmk). Main Outcome Measure(s): Morphological development of the embryo, proportion of fragmented embryos, caspase-3-like activity, DNA breakage, and phosphatidylserine exposure in blastomeres. Result(s): The proportion of embryo reaching two-cell, three- to four-cell, and morula stage at 48, 72, and 96 hours after hCG administration, respectively, were comparable between the control embryos and those treated with either z-VAD-fmk or z-DEVD-fmk, at three concentrations (10 muM, 50 muM, and 200 muM) Although the inhibitors suppressed the caspase-3-like activity in the embryo fragment before compaction and decreased DNA breakages, there was no statistically significant difference in the percentage of fragmented embryo between the control and those treated with caspase inhibitors. The inhibitors did not affect the incidence of phosphatidylserine exposure in the blastomere of the treated embryos. Conclusion(s): Cytoplasmic fragmentation in precompaction mouse embryos is not a consequence of caspase-related apoptosis. (Fertil Steril(R) 2001;75:986-91. (C) 2001 by American Society for Reproductive Medicine.).