Prim’Holstein heifers selected for “Fertil-” homozygous haplotype of QTL-F-Fert-BTA3 showed a higher rate of early pregnancy failure and slower embryo development after in vitro maturation (IVM) suggesting lower oocyte quality. We aimed to ascertain intrafollicular factors related to lower oocyte quality in “Fertil-” cows. Analysis of individual oocytes showed meiotic progression delay in “Fertil-” as compared to “Fertil+” dairy cows after in vivo and in vitro maturation (p<0.05). Expression of several genes localized to QTL-F-Fert-BTA3 or related to meiosis and MAPK pathway were analyzed in individual metaphase-II oocytes by real-time PCR. Energy metabolism, apoptosis, extracellular matrix and QTL’s genes were analyzed in surrounding CC. In vivo, significant decrease in prostaglandin synthase PTGES1 and PTGS2 expression coupled with lower PTGS2 protein abundance in cumulus cells (CC) and reduced expression of MOS in enclosed metaphase-II oocytes from “Fertil-” cows was observed. IVM strongly deregulated gene expression in CC and in oocytes as compared to in vivo; nevertheless, differential expression of several genes including MOS was observed between the two haplotypes. During IVM, PTGS2 activity inhibitor NS398 (50μM) led to lower expression of FASN (fatty acid synthase) in CC and of MOS in treated metaphase-II oocytes. By immunofluorescence, MOS protein was localized to a midbody-like contractile ring separating the polar body from the ooplasm, suggesting a role in the terminal stage of oocyte maturation. Our results suggest that factors involved in prostaglandin synthesis and lipid metabolism in CC could impair oocyte maturation and might be involved in the reduced fertility of “Fertil-” cows.