Phenotypic Analysis of Preimplantation Lethality in Mice

Preimplantation development covers a period of ∼4.5 d from fertilization to implantation in the uterus. If a homozygous mutant phenotype causes the death of embryos during this period, simple culture methods are available that support preimplantation development to allow a thorough morphological assessment. Embryos are recovered from the oviducts or uterus and examined for gross morphology, cell number, and progression through cleavage stages. Blastocysts can also be cultured over the implantation period and undergo a process analogous to implantation in vitro. Different categories of phenotypes such as failure of compaction, abnormal blastocyst formation, or failure to hatch from the zona pellucida and failure to attach and outgrow in vitro are discussed in relation to what each phenotype might portend. Further experimental procedures such as isolation and assessment of blastocyst inner cell mass and analysis of induced implantation delay in vivo may also be appropriate. Additional assessment of preimplantation embryos can involve histology and localization of mRNA or proteins either in sections or whole embryos.