Metabolomics and correlation network analysis of follicular fluid reveals associations between L-tryptophan, L-tyrosine and polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder in women of reproductive age. Some studies have investigated metabolic alterations in plasma and follicular fluid from PCOS patients, but they did not control for obesity or insulin resistance (IR); additionally, correlation analysis of metabolites is sparse. Accordingly, in this study, we aimed to examine metabolic differences owing to the pathogenesis of PCOS, identify the hub metabolites and investigate its associations with androgens. We applied GC-MS platform coupled with a correlation network approach to analyze follicular fluid samples from 32 PCOS patients without obesity and IR and 31 healthy women. Thirty significantly altered metabolites in PCOS patients were enriched in amino acid metabolism. l-Phenylalanine, l-tryptophan, pyroglutamic acid, l-tyrosine, l-leucine and l-valine were screened as hub metabolites in metabolic correlation network. Among them, increased l-tryptophan and l-tyrosine were altered hub metabolites, and they had a more significant impact on the metabolic change of PCOS. In addition, l-tryptophan and l-tyrosine were significantly positively associated with serum androgens levels in the PCOS. Our results suggest that disorders of amino acid metabolism, especially tryptophan and tyrosine metabolism, might play an important role in the development of PCOS in predisposed women without obesity and IR.

Automated summary

This study investigated metabolic differences in follicular fluid samples from PCOS patients and healthy women, identifying significantly altered metabolites enriched in amino acid metabolism. Two hub metabolites, l-tryptophan and l-tyrosine, were found to have a significant impact on metabolic changes in PCOS and were positively associated with serum androgen levels in PCOS patients. The results suggest that amino acid metabolism, particularly tryptophan and tyrosine metabolism, may play an important role in the development of PCOS in predisposed women without obesity and IR.