Sex differences in the sleep architecture and sleep-disordered breathing in C57BL/6J mice

Sex differences in sleep disorders have been reported. Sleep-disordered breathing (SDB) is more prevalent in men, whereas women are more prone to insomnia. Mouse models have been extensively used in sleep research, but sex differences are not routinely taken into account. We performed a comprehensive examination of sleep architecture, breathing during sleep, and chemosensitivity in male and female C57BL/6J mice.

Mice instrumented with electroencephalogram/electromyogram electrodes underwent full-polysomnography inside a whole-body plethysmography chamber. Ventilatory responses to hypoxia (10% O2, 3% CO2) and to two regimens of hypercapnia (8% CO2 balanced in 20.9% O2  vs 8% CO2 balanced in 65% O2) were measured. Female mice underwent bilateral ovariectomy (OVX) and repeated the assessments.

Female mice showed more frequent arousals from sleep, increased apnea frequency and increased respiratory variability compared to males. Hypoxic chemoreflex did not differ between sexes, but CO2 chemosensitivity was significantly augmented in females. The carotid body inactivation by hyperoxia attenuated CO2 chemoreflex responses in females, but not in males. OVX reduced CO2 chemosensitivity, but did not affect respiratory variability, while the apnea index increased.

In C57BL/6J mice, we found significant sex differences in sleep. Females manifested a more severe SDB phenotype characterized by more frequent arousals and heightened CO2 responsiveness compared to males. Our findings also suggested that more robust peripheral CO2 chemoreflexes may account for sleep disruptions in female mice. Our findings further implicate ovarian hormones in respiratory control.