47 Effect of a long-term, high-fat diet on metabolic health and oocyte quality of an outbred (Swiss) versus inbred (C57BL/6N) mouse strain

Maternal metabolic disorders like obesity and diabetes type II are known to affect reproductive physiology, ultimately leading to poor fertility. The oocyte and embryo are extremely vulnerable during the periconceptional period to metabolic stressors, leading to disappointing fertility results. Most mouse model research regarding obesity and Western type diets has been performed on the inbred C57BL/6 strain. However, inbred strains are often linked with decreased fertility. Relying only on inbred strains might also limit translation to human (outbred) physiology. To further explore this, we compared the inbred C57BL/6N to an outbred Swiss strain. Five-week-old Swiss (N=30) and C57BL/6N (B6) (N=29) mice were fed a control (CTRL) or a high-fat (HF) diet for 13 weeks. Diets differed in percentage of fat (10% v. 60%). Body weight gain, serum profile (nonesterified fatty acids, cholesterol, and triglycerides), and oocyte quality were studied. Mature oocytes were collected after hormonal stimulation (IP injection of 10IU of pregnant mare serum gonadotropin followed by 10IU of hCG 48h later). To study oocyte quality, Bodipy (lipid droplets), JC-1 (mitochondrial membrane potential), and Cell-Rox Deep Red stainings were performed, as well as transmission electron microscopy to examine mitochondrial structures. All data were analysed using the t-test. In comparison with the CTRL group, the HF diet increased body weight by 18.09 and 27.87% in Swiss and B6, respectively. The HF significantly increased blood cholesterol levels (103.5v. 143.1 mg/dL in Swiss mice, 141.8v. 185.4 mg/dL in B6 mice) in both strains, and tended to increase blood nonesterified fatty acids (P=0.053) and triglycerides (P=0.075) only in Swiss but not in B6 mice. Oocytes collected from the HF diet group contained a larger total volume of lipid droplets (P