Genome-wide DNA methylation patterns in IVF-conceived mice and their progeny: A putative model for ART-conceived humans

The aim of this study was to use a mouse model to gain an understanding of the safety of reproduction between humans conceived through assisted reproductive technology (ART). Mice derived from in vitro fertilization and embryo transfer (IVF-ET) were crossed. Their behavior, morphology, histology and genome-wide DNA methylation status in the brain were examined by the Morris water maze, H&E staining and methylated DNA immunoprecipitation coupled with DNA methylation microarrays. Although no significant differences in behavior or morphology were observed, we did find small clusters of CpG islands and promoters that were aberrantly methylated. Hypermethylation was more common than hypomethylation in each of the two generations. Some of the aberrant methylated promoters were validated by bisulfite sequencing. Our results show that IVF may slightly modify the somatic methylation pattern and that some of this aberrant methylation might be inherited by the following generation.

► We built mouse models conceived by in vitro fertilization.
► Intergenerational inheritance of DNA methylation patterns were evaluated genome-widely.
► A small cluster of CpG islands and promoters were found aberrantly methylated.
► Some of these aberrant methylations may be inherited by the following generation.