Metabolomic profiling of serum in aging mice supplemented with tocotrienol-rich fraction for identification of female reproductive aging biomarkers

Abstract

Ovarian aging has been associated with increased oxidative stress leading to loss of ovarian function and infertility. Tocotrienol, a potent antioxidant, has been proven to exert beneficial effects in the female reproductive system. Serum metabolites were analyzed to examine the biochemical changes and to identify biomarkers related to reproductive aging that could lead to poor embryo quality and development. Female Mus musculus mice were divided into four groups. Six-month-old mice were given tocopherol-stripped corn oil as a vehicle control while other groups were supplemented orally with tocotrienol-rich fraction (TRF) at doses of 90, 120, and 150 mg/kg bodyweight for two months, respectively. After two months, mice from all groups were super ovulated, and euthanized. Embryos were collected at the 2-cell stage and cultured to monitor their development while serum was used for metabolomic analysis. The percentage of normal embryos and development of embryos to blastocyst stage were significantly higher in groups supplemented with TRF. A total of 71 metabolites that are related to reproductive aging were identified in all groups and significant changes were detected in metabolic pathways that include fatty acids, amino acids metabolism and steroid hormone biosynthesis. These changes suggest that aging has a negative impact on cellular energy storage, energy metabolism and oxidative stress that subsequently affect female fertility. Supplementation with TRF prevented the impact of age related metabolic changes on the embryo. Thus, it appears that TRF exerts a protective mechanism towards female reproductive aging.