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 fragmentatio n 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: benzyl oxycarbonyl-Val-Ala-Asp fluoromethylketone (z-VAD-fmk) and benzyloxycarbony l-Asp-glu-Val-Asp-fluoromethyl ketone (Z-DEVD-fmk). Main Outcome Measure(s): Morphological development of the embryo, proportio n of fragmented embryos, caspase-3-like activity, DNA breakage, and phospha tidylserine 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, respect ively, were comparable between the control embryos and those treated with e ither 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 w as no statistically significant difference in the percentage of fragmented embryo between the control and those treated with caspase inhibitors. The i nhibitors did not affect the incidence of phosphatidylserine exposure in th e 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;75:9 86-91. (C) 2001 by American Society for Reproductive Medicine.).