Single-cell multiomic analysis reveals methylome and transcriptome deviations following oocyte maturation in vitro

In vitro maturation is an essential tool in reproductive technologies, though its impact on oocyte quality remains a concern. This study shows that in vitro maturation alters gene expression and DNA methylation in bovine oocytes compared to in vivo matured oocytes, potentially compromising oocyte quality and developmental competence.

In vitro maturation of oocytes is a routine step in assisted reproduction but is associated with lower embryo development rates compared to oocyte maturation in vivo. We analyzed the genomic profiles of oocytes from the same cow, either matured in vivo or in vitro, using single-cell methylome and transcriptome sequencing, along with transcriptome analysis of corresponding cumulus cells. Both the transcriptome and methylome of the oocytes matured in vitro were altered. Notable changes included alterations in CpG islands associated with imprinted genes, including decreased methylation levels in MEST (PEG1), NNAT (both implicated in large offspring syndrome), and MIMT1. Transcriptomic analysis of their cumulus cells highlighted impaired mitochondrial function, hypoxia responses, and cell adhesion. Our findings highlight the extent to which the maturation environment can influence key epigenetic regulators and mRNA profiles that affect oocyte quality and subsequent developmental outcomes. The data provide a valuable resource for optimizing assisted reproductive technologies.