Female Mice Show More Severe Sleep-Disordered Breathing, Driven by Heightened CO2 Sensitivity
Sex differences in sleep-disordered breathing are well documented in humans: men are more likely to have obstructive sleep apnea, while women report more insomnia. But the underlying biological mechanisms remain poorly understood. A new study in Sleep from researchers at George Washington University and Johns Hopkins University provides evidence from a mouse model that female sex itself, mediated by ovarian hormones, may drive a more severe sleep-disordered breathing phenotype.
What they found
Dashdulam Davaanyam and colleagues implanted C57BL/6J mice with EEG and EMG electrodes and recorded full polysomnography inside a whole-body plethysmography chamber. They then tested respiratory responses to hypoxia (low oxygen) and hypercapnia (elevated carbon dioxide), and repeated all measurements in female mice after ovariectomy.
Female mice showed significantly more sleep fragmentation than males, with more frequent arousals. They also had a higher apnea index and greater respiratory variability during sleep. The key physiological difference: female mice had markedly augmented CO2 chemosensitivity. Their ventilatory response to hypercapnia was stronger than in males, and this difference depended on the peripheral chemoreceptors, specifically the carotid bodies. Inactivating the carotid bodies with hyperoxia eliminated the CO2 hyperresponsiveness in females but had no effect in males, localizing the sex difference to peripheral chemosensing.
Ovariectomy in female mice reduced CO2 chemosensitivity, confirming that ovarian hormones contribute to the heightened response. However, the apnea index increased after ovariectomy, suggesting that ovarian hormones may play a dual role: amplifying chemosensitivity while also protecting against apneas.
Hypoxic chemoreflexes showed no significant difference between sexes.
Why it matters
This study provides a mechanistic framework for understanding sex differences in sleep-disordered breathing at the level of neural circuits and hormones. The finding that peripheral chemoreceptors drive the female CO2 hyperresponsiveness is novel and points to the carotid body as a potential therapeutic target for sex-specific treatments.
The dual role of ovarian hormones raising CO2 sensitivity while reducing apnea frequency complicates the picture and may help explain the observed human patterns, where premenopausal women have lower apnea prevalence than men but postmenopausal women partially lose that protection. The ovariectomy data in mice mirror this menopausal transition.
Limits
The study was conducted in C57BL/6J mice, a single inbred strain. Findings may not translate directly to humans, and the relationship between CO2 chemosensitivity and clinical sleep apnea is not fully mapped across species. The sample size and specific estrus cycle timing were not detailed in the available abstract.
Bottom line
Female mice exhibit more severe sleep-disordered breathing than males, characterized by more arousals, higher apnea frequency, and augmented CO2 sensitivity driven by the carotid bodies and modulated by ovarian hormones. These findings provide a biological foundation for understanding sex differences in human sleep apnea and suggest the peripheral chemoreflex as a target for sex-specific interventions.
Source
Davaanyam D, et al. Sex Differences in the Sleep Architecture and Sleep-Disordered Breathing in C57BL/6J Mice. Sleep. 2026 Jun 27:zsag176. doi: 10.1093/sleep/zsag176. PMID: 42364162.