Species-specific differences in cumulus support during final oocyte maturation in mice and cattle

In brief: Cumulus support is more critical for bovine than murine oocytes during in-vitro maturation (IVM), affecting transzonal projection maintenance, organelle remodeling, molecular signatures, and meiotic progression. These species-specific differences support the bovine oocyte as the more informative experimental model for translational human IVM. Abstract: Cumulus-oocyte communication is a key regulator of oocyte maturation; however, comparative studies across species relevant to the choice of models for human in-vitro maturation (IVM) remain insufficient. We compared bovine and murine germinal vesicle oocytes matured in vitro as cumulus-oocyte complexes (COCs), denuded oocytes (DOs), or DOs cocultured with cumulus cells (DOs + CCs) to define species-specific dependence on cumulus support. Structural, organelle, molecular markers, transzonal projections (TZPs), connexin 37/43 expression, mitochondrial redistribution, lipid droplet remodeling, BAX/BCL2 ratios, DNMT3A/Dnmt3a expression, and maturation rate. In both species, IVM of COCs reduced TZP signal, but the decline was greater in cattle. Denudation revealed a marked divergence: bovine DOs showed near-complete TZP loss, retention of immature-like mitochondrial organization, impaired lipid remodeling, altered BAX/BCL2 and DNMT3A expression, and reduced maturation, whereas murine DOs preserved TZP features, underwent mitochondrial redistribution comparable to COCs, and maintained maturation rates. Cumulus coculture restored most parameters to COC-like levels in mice but only partially in cattle. Lipid remodeling also differed by species, with increased droplet number in bovine oocytes and fewer but larger droplets in murine oocytes. Bovine oocyte maturation was the highest in hormone-supplemented media in COCs and decreased after denudation, whereas mouse oocyte maturation was similar in COCs and DOs regardless of the hormone presence in culture media. These findings show that cumulus-oocyte communication is regulated in a species-specific manner during IVM and identify the bovine oocyte as a more appropriate model for translational human IVM studies that depend on intact cumulus support.