Tryptophan metabolism emerges as a key regulator of female reproductive health
A new review published in the Chinese Medical Journal has highlighted the potentially important role of tryptophan metabolism in female reproductive health, extending beyond its traditional association with fertility. The review, titled “Tryptophan metabolism: A hidden regulator of female reproductive health beyond fertility,” examines how tryptophan-derived metabolites influence ovarian function, pregnancy, and maternal–fetal health.
Tryptophan is an essential amino acid and the only amino acid containing an indole ring. In the body, it is primarily metabolized through three pathways: the kynurenine (Kyn) pathway, serotonin pathway, and indole pathway. These pathways generate bioactive metabolites involved in inflammation, immune regulation, metabolic homeostasis, and neurological function.
According to the review, tryptophan metabolism can influence reproduction both indirectly, by regulating inflammation, oxidative stress, metabolic disturbances, and aging, and directly by modifying the ovarian microenvironment, follicular development, and hormone secretion.
The serotonin pathway generally appears to exert protective effects. Serotonin and its derivative melatonin may help protect oocytes and granulosa cells against oxidative damage while supporting follicular development and hormone secretion.
The kynurenine pathway, meanwhile, appears to have more complex effects. Kynurenine is associated with oxidative stress, metabolic abnormalities, and ovarian aging, although nicotinamide adenine dinucleotide (NAD⁺), a downstream product of this pathway, may have anti-aging effects and help preserve ovarian reserve.
The indole pathway may influence reproductive health through the gut–reproductive axis, linking intestinal microbial metabolism with the maternal internal environment.
The review notes that disruptions in tryptophan metabolism have been observed in several conditions affecting ovarian function. Metabolomic studies have reported significantly reduced levels of tryptophan and indole metabolites in follicular fluid among women with diminished ovarian reserve (DOR). The kynurenine pathway has also been reported to show abnormal activation in polycystic ovary syndrome (PCOS).
These findings suggest that altered tryptophan metabolism could contribute to reproductive dysfunction through interactions involving oxidative stress, metabolism, inflammation, and ovarian aging.
The role of tryptophan metabolism may continue beyond conception. During pregnancy, tryptophan-derived metabolites participate in embryo implantation, maternal immune adaptation, and fetal development. The pathway contributes to immune tolerance between the mother and fetus, while disturbances have been associated with pregnancy complications, including preeclampsia.
Maternal tryptophan availability may also influence maternal mental health and fetal neurological and immune development, underscoring the broader importance of adequate tryptophan metabolism during pregnancy.
The review identifies several potential strategies for targeting tryptophan metabolism, including dietary supplementation, gut microbiota modulation, inhibition or regulation of key enzymes such as indoleamine 2,3-dioxygenase (IDO), and melatonin-based antioxidant approaches.
However, the authors emphasize that many of these approaches remain at the theoretical or preclinical stage, with substantial evidence coming from animal and mechanistic studies. Further research is needed to establish precise molecular mechanisms, identify cell-specific targets, and determine whether these interventions can safely improve reproductive outcomes in humans.
The review positions tryptophan metabolism as a potential link between ovarian biology, systemic metabolic and immune regulation, and maternal-fetal health, providing a framework for investigating new therapeutic approaches to female reproductive disorders.
References
- Wu Q, Zeng F, Qiao J, Qi X. Tryptophan metabolism: A hidden regulator of female reproductive health beyond fertility. Chin Med J. 2026;139(13):1943-1958. doi:10.1097/CM9.0000000000004145.