Metabolomic profiling of exosomes reveals age-related changes in ovarian follicular fluid

BACKGROUND: Female fertility declines with increased maternal age, and this decline is even more rapid after the age of 35 years. Follicular fluid (FF) is a crucial microenvironment that plays a significant role in the development of oocytes, permits intercellular communication, and provides the oocytes with nutrition. Exosomes have emerged as being important cell communication mediators that are linked to age-related physiological and pathological conditions. However, the metabolomic profiling of FF derived exosomes from advanced age females are still lacking. METHODS: The individuals who were involved in this study were separated into two different groups: young age with a normal ovarian reserve and advanced age. The samples were analysed by using gas chromatography-time of flight mass spectrometry (GC-TOFMS) analysis. The altered metabolites were analysed by using Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to identify the functions and pathways that were involved. RESULTS: Our data showed that metabolites in exosomes from FF were different between women of young age and women of advanced age. The set of 17 FF exosomal metabolites (P ≤ 0.05) may be biomarkers to differentiate between the two groups. Most of these differentially expressed metabolites in FF were closely involved in the regulation of oocyte number and hormone levels. CONCLUSIONS: In this study, we identified differences in the metabolites of exosomes from FF between women of young age and women of advanced age. These different metabolites were tightly related to oocyte count and hormone levels. Importantly, these findings elucidate the metabolites of the FF exosomes and provide a better understanding of the nutritional profiles of the follicles with age.