In vitro fertilization: a potential means for toxicity testing

Uses and potential uses of in vitro fertilization are: (1) a research tool for investigating biochemistry of fertilization, (2) an assay for fertilizing ability, (3) a potentially useful clinical approach for certain cases of infertility, and (4) a potentially useful means for improving animal breeding. In vitro fertilization methodology is sufficiently advanced for gametes of several mammalian species, especially mouse, rabbit, and rat, for use in evaluating effects imposed by toxic agents of environmental or genetic origin. Alteration of the normal events of fertilization and/or embryonic development following transfer of in vitro fertilized embryos into surrogate dams can serve as end point(s) in applying this means for toxicity testing. In vitro fertilization of mouse and rat ova has been explored as an alternative to in vivo fertilization in male contraceptive development studies. Original observations on toxicity of abnormal O(2) concentrations for rabbit fertilization in vitro are reported here. Ova were fertilized under 0, 20, 48, and 95% O(2), but toxicity from the extreme conditions, 0 and 95% was apparent from comparison of proportions of fertilized ova reaching the 4-cell stage during the 24-hr incubation. Toxicity was further evidenced by inability of embryos fertilized under 0 and 95% O(2) tensions, in contrast to those fertilized under 20% O(2), to sustain normal gestation following their transfer into recipient does. Recent success in the fertilization of cow ova in vitro in this laboratory provides encouragement to develop a useful means for testing normalcy of gametes in this species. Such studies might lead to useful screening procedures for avoidance of human infertility resulting from hazardous environmental conditions.