Epigenetic modifications modulate cell differentiation and lineage specification in multicellular organisms in part by regulating transcription of developmental genes. While it has been proposed that epigenetic programming of germ cells is critical for offspring development and post-natal health, the mechanisms involved are poorly understood. As environmental factors, such as drugs or diet, are proposed to alter germline epigenetic programming understanding these mechanisms is essential. Polycomb Repressive Complex 2 (PRC2) is an epigenetic modifier that catalyses the epigenetic modification, H3K27me3 and represses developmental gene expression in many tissues, including the germline. Using genetic models that lack PRC2 function specifically in the oocyte, we are examining how H3K27me3 establishment is regulated in the maturing oocyte. We demonstrate that oocytes are enriched with H3K27me3 during their growth and that genetic deletion of PRC2 activity alters offspring growth and development. Consistent with this, de novo germline mutations in PRC2 subunits result in Weaver or Cohen-Gibson Syndromes in humans, characterised by overgrowth, skeletal abnormalities and learning deficits. We are determining how these critical PRC2 catalytic and structural components (EZH2 and EED, respectively) epigenetically program oocytes and consequently regulate growth and development in offspring. Transcriptional analysis of oocytes lacking Eed revealed 244 significantly up-regulated genes (>2-fold), demonstrating that a primary function of PRC2 is to repress developmental genes in oocytes. In stark contrast, deletion of Ezh2 results in only 13 genes being significantly up-regulated (>2-fold). Furthermore, comparison of offspring phenotypes from mice lacking Eed or Ezh2 demonstrate that these PRC2 components differentially impact growth outcomes in offspring. Comparison of oocytes lacking Eed or Ezh2 is revealing how targeting these different PRC2 proteins results in differential outcomes in offspring development. This is critical for determining how exposure to clinically relevant EZH2 or EED inhibiting drugs impact on oocyte epigenetic programming, and consequent health and development in offspring.