Tryptophan catabolism to serotonin and kynurenine in women undergoing in-vitro fertilization

Abstract

This cross-sectional clinical study was designed to explore the impact of tryptophan-kynurenine and tryptophan-serotonin (5 HT) pathways on reproductive performance during in vitro fertilization (IVF). Paired serum and follicular fluid (FF) samples were obtained from 64 consecutive IVF patients. The analysis was done by using LC-MS/MS. Ovarian hyperstimulation resulted in decreased serum tryptophan (p<0.004), 5-HT (p<0.049) and kynurenine (p<0.001). FF levels of tryptophan (R=0.245, p<0.051), kynurenine (R=0.556, p<0.001) and 5-HT (R=0.523, p<0.001) were positively related to their respective serum levels. Clinical pregnancy was associated with higher serum 5-HT (p<0.045) and FF 5-HT (p<0.020) and lower kynurenine to 5-HT ratio (p<0.024). Chemical pregnancy was also positively related to FF 5-HT (R=0.362, p<0.024). Moreover, there was a direct relationship of the number of mature oocytes to the FF 5-HT (R=0.363, p<0.020) but it was inversely related to FF tryptophan to 5-HT and FF kynurenine to 5-HT ratios (R=-0.389, p<0.016 and R=-0.337, p<0.036, respectively). Multivariate logistic regression revealed that the number of mature oocytes was significantly influenced by FF 5-HT (?=0.473, p<0.001). In IVF patients ovarian hyperstimulation results in a reduction of the availability of tryptophan to catabolic pathways to kynurenine and 5-HT. Outcome measures improved significantly when 5-HT predominated over kynurenine.

Fig. 1

Tryptophan catabolism with particular reference to the kynurenine pathway. Abbreviations of the key enzymes involved in the kynurenine pathway: IDO: Indoleamine 2,3 – dioxygenase TDO: Tryptophane 2,3 – dioxygenase KYNU: Kynureninase KATs: Kynurenine aminotransferases KMO: Kynurenine 3-monooxygenase 3HAO: 3-hydroxyanthranilic acid oxygennase ACMSD: Aminocarboxymuconate-semi-aldehyde decarboxylase QPRT: Quinolinic acid phosphoribo-syltransferase