0278 Sexual Dimorphisms in Sleep-disordered Breathing of C57BL/6J Mice

Abstract Introduction Differences in sleep-disordered breathing (SDB) between biological sexes have been extensively reported. Prevalence of SDB is increased in men, but women appear to be more symptomatic at lower SDB severity, exhibiting more daytime sleepiness and insomnia symptoms. However, the mechanisms associated with sex differences in SDB remain unclear. We examined the differences in the sleep architecture and breathing during sleep between male and female mice with the same genetic background. We also analyzed whether ovariectomy abolishes the sex differences in SDB. We hypothesized that differences in sleep and SDB between male and female mice are attributed to different chemoreflex responses to carbon dioxide (CO2). Methods Mice were instrumented with EEG/EMG electrodes. Full-polysomnographies were performed in 16 males and 18 females C57BL/6J mice inside a whole-body plethysmography chamber. Poincaré plots of minute ventilation were used to assessed breathing stability during sleep. Mice were exposed to acute episodes of hypercapnia (8% CO2) and hypoxia (10% O2 + 3% CO2) during wakefulness and NREM sleep to measure the hypercapnic ventilatory response (HCVR) and hypoxic ventilatory response (HVR), respectively. Females underwent bilateral ovariectomy and the studies were repeated after 2 weeks. Results Sleep fragmentation was 55% increased in female mice compared to males. Unexpectedly, apnea index and breathing instability during sleep were significantly higher in female mice compared to males. HVR was similar between sexes. CO2 sensitivity positively correlated with apnea index (r=0.55, P=0.05). HCVR was significantly augmented in females during wakefulness and NREM sleep, which was attenuated by ovariectomy. Conclusion Our findings have shown different phenotypes of SDB between sexes in C57BL/6J mice. SDB in female mice is associated with a hyperarousal state and augmented CO2 sensitivity, which could be related to ovarian hormones. Support (if any) American Heart Association Postdoctoral Fellowship Award 828142 (to L.J.K.), NHLBI grant 2R01 HL133100-05, NIH R01 HL128970, and R01 HL13892 (to V.Y.P.), 1K23HL155730 and American Academy of Sleep Medicine Foundation 238-BS-20 (to L.V.P.)