Poor maternal sleep associates with adverse outcomes for mothers and offspring, and shifts in tryptophan metabolism via the kynurenine pathway (KP) are a candidate contributor. The authors report that pregnancy itself alters sleep-wake patterns in female rats: control-fed pregnant dams (ECon) displayed increased NREM and REM sleep during the dark phase compared with their non-pregnant baseline. These pregnancy-associated changes in nocturnal sleep were prominent features of the maternal sleep phenotype reported in the study.
The work emphasizes that pregnancy does not simply produce uniform sleep loss; rather, it reshapes timing and amounts of sleep across circadian phases. This baseline remodeling of sleep during gestation sets the context in which KP activation and experimental kynurenine supplementation exert additional, and sometimes attenuated, effects.
To model enhanced KP metabolism during gestation, investigators used the embryonic kynurenine (EKyn) approach: maternal diet was supplemented with kynurenine, the initial KP metabolite, during the last week of gestation. The study employed a within-subject design, allowing comparison of sleep-wake parameters in the same females when pregnant and when non-pregnant. Alongside behavioral polysomnographic endpoints, the authors measured kynurenic acid (KYNA) — a neuroactive KP metabolite — in brain tissue and saliva to probe central and peripheral KP activation.
The within-subject design strengthens detection of pregnancy-modulated effects of kynurenine by controlling for inter-animal variability in baseline sleep patterns and KP tone.
In the ECon group (no kynurenine supplementation), pregnancy increased both dark-phase NREM and REM sleep relative to the animals' non-pregnant baseline. The authors present these changes as characteristic maternal adaptations: the dark (active) phase showed greater amounts of both NREM and REM, indicating a reorganization of sleep across the circadian cycle during late gestation.
No reduction of light-phase REM near parturition was observed in ECon dams, distinguishing the control pregnancy phenotype from the kynurenine-supplemented condition.
EKyn dams retained much of the pregnancy-associated increase in dark-phase NREM and REM observed in controls. However, a notable divergence emerged around parturition: EKyn dams showed a reduction in light-phase REM sleep near delivery that was not present in the ECon group. Thus, gestational KP augmentation did not abolish the broad pregnancy-driven nocturnal sleep increases but did produce a specific REM deficit in the light phase proximate to parturition.
The data indicate that pregnancy attenuates some KP-related effects on sleep but does not fully protect against KP-associated REM disruption, particularly during the peripartum window.
When the same females were tested in the non-pregnant state, kynurenine supplementation produced a stronger and more consistent phenotype: non-pregnant, kynurenine-fed females exhibited reduced light-phase REM sleep across treatment days. This contrast suggests that the pregnant brain is less susceptible to some consequences of KP activation on REM expression than the non-pregnant brain, though certain vulnerabilities (for example near parturition) remain.
Overall, the kynurenine-associated sleep phenotype was more robust outside pregnancy, and during pregnancy the additional effects of dietary kynurenine were detectable mainly when compared to the animals' own non-pregnant baseline rather than as large differences between pregnant treatment groups.
The investigators quantified KYNA in both brain tissue and saliva. Salivary KYNA distinguished kynurenine-fed females from matched controls, and salivary KYNA levels correlated with brain KYNA. These observations suggest that saliva may serve as a peripheral biomarker reflecting central KP activation in this model, with potential utility for noninvasive monitoring of KP metabolites in preclinical or translational contexts.
The reported correlation provides preliminary support for using salivary KYNA as an accessible readout of brain KP activity; exact correlation coefficients and statistical details were reported in the source article.
The authors conclude that pregnancy reshapes maternal sleep architecture and attenuates but does not eliminate KP-associated REM sleep disruption. Elevated brain KYNA is implicated as a potential mediator of maternal sleep regulation and of the REM perturbations observed with kynurenine supplementation.
Limitations noted by the authors include that this report is a preprint and the findings have not been peer reviewed. The EKyn model uses dietary kynurenine supplementation during late gestation as a proxy for enhanced KP metabolism; extrapolation to human pregnancy requires caution. The study focused on late gestation and near-parturition windows, and effects at other stages were not reported here.
Translationally, the work raises the possibility that KP activation during pregnancy could influence maternal sleep and that peripheral measures such as salivary KYNA might help detect central KP changes. Further research, including peer-reviewed replication and studies addressing mechanisms and timing across gestation, would be needed before clinical application.
Funding for the work included NIH grants and support from the American Academy of Sleep Medicine Foundation. The authors declared no competing interests. Because this is a preprint, readers should interpret the findings with recognition that the report has not undergone formal peer review.