Neonatal stress favors age related rise in sleep apnea and metabolic comorbidity in female rats

Introduction: In women, the natural loss of ovarian function during menopause is associated with an increase in the number of cases of sleep apnea and its comorbidities, such as hypertension and obesity. However, only a subpopulation of women is affected by these disorders, a trajectory that is misunderstood. We know that stress and childhood adversity are linked with a sex specific increase in disease susceptibility in adults. In mammals, exposure to neonatal maternal separation (NMS) is an established pre-clinical model to address the consequences of early life stress. Therefore, we hypothesized that NMS increases respiratory control disorder and favors obesity in 1-year old female rats. Methodology: Rat pups were either undisturbed (CTRL) or subjected to NMS during which pups were placed in a temperature-controlled incubator 3h/day from postnatal day 3 to 12. At 60 weeks of age, we measured apnea frequency during sleep and chemoreflex response to hypoxia (10% O2; 40s) or hypercapnia (5% CO2; 10 minutes) using a whole-body plethysmography system. We also measured body weight and body length (to calculate the body mass index (BMI – g/cm2)), % of fat (using a magnetic resonance equipment – BRUKER) and leptin levels in the plasma (by Luminex® technology, a bead-based immunoassay). Results: Apnea frequency of NMS females was 20% higher than CTRL; the ventilatory responses to hypoxia and hypercapnia were also significantly greater (30% and 94% respectively). The BMI of NMS was 18% higher than CTRL and greater than the threshold for obesity. Additionally, those animals presented 5% more fat in their body composition, 5% less lean tissue and the same % of fluids. As for leptin, the mean values were similar but the variation in blood levels was 34% higher in NMS than in CTRL. Conclusions: Age-related loss in ovarian function reveals the latent effects of early life stress on respiratory control. By predisposing to obesity and interfering with leptin signaling, NMS also favors metabolic disturbance commonly observed in ageing women. These data suggest that stress is an important factor in the development of sleep apnea and related co-morbidities in a subpopulation of menopausal women. DAM is supported by the FRQ-S (268346) and the ‘Programme de complément de bourse’ from RSRQ (2021-22). This research is supported by the Canadian Institutes of Health Research (RK). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.