Trophectoderm biopsies of blastocysts for preimplantation genetic testing following in vitro fertilization and embryo culture increases epigenetic dysregulation in a mouse model [RNA-seq]
Trophectoderm biopsy for preimplantation genetic testing (TEBx) impacts placental and embryonic health during early development, with some alterations resolving while others worsening later in development. We observed that at E12.5, IVF + TEBx had a worse outcome in terms of changes in DNA methylation and differential gene expression in placentas and whole embryos compared with IVF alone. These changes were reflected in alterations in placental morphology and blood vessel density. At E18.5, early changes in embryos were maintained or worsened, while molecular and morphological changes in the placenta were not different from the IVF group, except for changes in blood vessel density, which persisted. Of note is that most differences were sex specific. We conclude that TEBx has more detrimental effects in both mid-gestation placental and embryonic tissues, with changes in embryonic tissues persisting or worsening in later developmental stages compared to IVF alone. Additionally, consistent with previous work, we report sex differences in the observed effects. Finally, we identified that the addition of vitrification after TEBx has a more pronounced detrimental effect on placental and fetal health. Our findings provide additional support that more studies should be done to assess the impact of new procedures during ART to ensure healthy pregnancies and offspring outcomes. Overall design: Gene expression analysis using Total RNA extracted from E12.5 placenta n=30 (F=15 and M=15), E12.5 whole fetus n=30 (F=15 and M=15), E18.5 placentas (F=15 and M=15) and E18.5 fetal livers (F=15 and M=15) from 3 different groups Natural, IVF and IVF+TEBx were sequenced using Illumina NovaSeq6000