1 Fatty Acid Metabolism during Maturation Affects Glucose Uptake and is Essential to 1 Oocyte Competence

15 Fatty acid oxidation (FAO) is essential for oocyte maturation in mice. The objective of this 16 experiment was to determine the effect of etomoxir (a FAO inhibitor; 100 μM), carnitine (1 17 mM), and palmitic acid (1 or 100 μM) during maturation on metabolism and gene expression of 18 the oocyte and cumulus cells, and subsequent embryo development in the mouse. Carnitine 19 significantly increased embryo development, while there was a decrease in development 20 following maturation with 100 μM palmitic acid or etomoxir (P<0.05). Glucose consumption 21 per cumulus-oocyte-complex (COC) was decreased after treatment with carnitine and increased 22 following etomoxir treatment (P<0.05). Intracellular oocyte lipid content was decreased after 23 carnitine or etomoxir exposure (P<0.05). Abundance of Glut1 was increased after etomoxir 24 treatment in the oocyte and cumulus cells (P<0.05), suggesting stimulation of glucose transport 25 and potentially the glycolytic pathway for energy production when FAO is inhibited. Abundance 26 of Cpt2 tended to increase in oocytes (P=0.1) after treatment with 100 μM palmitic acid and in 27 cumulus cells after exposure to 1 μM palmitic acid (P=0.07). Combined with carnitine, 1 μM 28 palmitic acid increased abundance of Acsl3 (P<0.05) and Cpt2 tended to increase (P=0.07) in 29 cumulus cells, suggesting FAO was increased during maturation in response to stimulators and 30 fatty acids. In conclusion, fatty acid and glucose metabolism are related in the mouse COC, as 31 inhibition of FAO increases glucose consumption. Stimulation of FAO decreases glucose 32 consumption and lipid stores, positively affecting subsequent embryo development, while an 33 overabundance of fatty acid or reduced FAO negatively affects oocyte quality. 34 Page 2 of 44