Malonic acid (MA) is a dicarboxylic acid that inhibits the mitochondrial electron transport chain. Cumulus cells surrounding human oocytes that achieve conception after in vitro fertilization (IVF) contain higher levels of MA than those that do not. Although MA has no effect on embryo developmental culture, the effects of MA on cumulus cells and oocyte quality remain unclear. In this study, the addition of 10 μM MA to the in vitro maturation (IVM) medium cultured cumulus cell-oocyte complexes improved embryo production efficiency, meeting multiple conception-related criteria after IVF (P < 0.05). MA did not affect the nuclear maturation rate of oocytes after IVM; however, it increased lipid content and normal alignment ratio of cortical granules (P < 0.05), both of which are indicators of cytoplasmic maturation of oocytes. MA also increased the adenosine triphosphate (ATP) content in oocytes only when they were present with cumulus cells (P < 0.05). MA decreased mitochondrial membrane potential activity in cumulus cells but increased the ATP content and enhanced glycolytic activity (P < 0.05). The use of a glycolysis inhibitor resulted in a decrease in the ATP content of both cumulus cells and oocytes and reduced the amount of lipids in oocytes (P < 0.05). These results indicate that MA shifts ATP production in cumulus cells from the mitochondrial to the glycolytic pathway, resulting in improved ATP synthesis. Furthermore, an increased ATP supply from cumulus cells to oocytes promotes oocyte cytoplasmic maturation, leading to improved quality of IVF embryos.
Itami et al. (2026) studied this question.