Sex Differences in Sleep-Disordered Breathing: Study Finds Female Mice Have More Disrupted Sleep and Stronger CO2 Sensitivity
Lead. Sleep-disordered breathing affects millions of people worldwide, and men and women experience it differently. A new study published in the journal Sleep provides fresh insight into the biological roots of these differences, using mice to show that females exhibit a more severe sleep-disordered breathing phenotype, with more frequent arousals from sleep and heightened sensitivity to carbon dioxide. The findings also point to a protective role for ovarian hormones against apneas.
What they found. Researchers at George Washington University and Johns Hopkins University performed full polysomnography on adult C57BL/6J mice implanted with EEG and EMG electrodes while housed inside whole-body plethysmography chambers. This setup allowed them to simultaneously record brain activity, muscle tone, and breathing patterns, giving a comprehensive picture of sleep architecture and respiratory stability.
The results revealed clear sex-based differences. Female mice woke up from sleep significantly more often than males, indicating greater sleep fragmentation. They also showed a higher frequency of apneas and greater respiratory variability, meaning their breathing was less stable during sleep. Together, these measures point to a more pronounced sleep-disordered breathing profile in females.
To understand the mechanisms behind these differences, the team tested the animals chemosensitivity, or how vigorously the respiratory system responds to changes in blood gases. When exposed to low oxygen (hypoxia), male and female mice responded similarly; there was no significant sex difference in the hypoxic chemoreflex. But the picture changed with carbon dioxide. Female mice showed a significantly augmented ventilatory response to hypercapnia (elevated CO2), suggesting their respiratory control centers are more sensitive to CO2 than those of males.
To pinpoint where this heightened CO2 sensitivity originates, the researchers performed a carotid body inactivation experiment. The carotid bodies are peripheral chemoreceptors located at the bifurcation of the carotid arteries; they sense changes in blood gases and send signals to the brainstem to adjust breathing. By exposing the mice to hyperoxia, which dampens carotid body activity, the team found that the augmented CO2 response in females was selectively reduced. The same manipulation had no effect in males. This indicates that the peripheral chemoreceptors, not central brainstem circuits, are the primary drivers of the female CO2 hyperresponsiveness.
The study also probed the role of ovarian hormones. A separate group of female mice underwent bilateral ovariectomy (OVX), surgically removing the ovaries and eliminating the main source of circulating estrogen and progesterone. Ovariectomy produced a striking set of results. CO2 chemosensitivity dropped significantly, directly implicating ovarian hormones in the modulation of respiratory drive. The apnea index, however, actually increased after OVX, suggesting that ovarian hormones normally protect against apneas. Respiratory variability was unchanged, indicating that different aspects of breathing control are regulated through distinct pathways.
Why it matters. Sex differences in sleep-disordered breathing are well documented in humans. Premenopausal women have a lower prevalence of obstructive sleep apnea than men of the same age, but the gap narrows after menopause, and women tend to report different symptoms and have different health outcomes than men. Animal models allow researchers to isolate biological mechanisms from the many confounding factors present in human studies, such as differences in body weight, airway anatomy, and lifestyle.
This study provides a mechanistic account of how female biology, through ovarian hormones and enhanced peripheral chemosensitivity, may shape breathing during sleep. The finding that peripheral chemoreceptors drive the female CO2 hyperresponsiveness is particularly notable, because it suggests a specific therapeutic target. Carotid body activity can be modulated pharmacologically, and if the same mechanism operates in humans, it could open avenues for sex-specific treatments for sleep apnea and related disorders.
The increased apnea frequency in the absence of ovarian hormones also carries implications for understanding postmenopausal sleep-disordered breathing in women. If ovarian hormones are protective against apneas, their decline after menopause could contribute to rising apnea risk, consistent with human epidemiological data.
Limits. As an animal study, direct translation to human physiology requires caution. Mice have different sleep patterns, respiratory mechanics, and hormonal cycles than humans, including a four-day estrous cycle rather than a monthly menstrual cycle. The study used a single mouse strain (C57BL/6J), so genetic background effects on the results are unknown. Ovariectomy removes all ovarian hormones at once, which does not perfectly model the gradual hormonal changes of human menopause. Additionally, the study examined young adult mice; age-related changes in sleep and breathing were not addressed.
Bottom line. Female mice have more fragmented sleep and more severe sleep-disordered breathing than males, driven in part by heightened peripheral CO2 chemosensitivity. Ovarian hormones appear to play a dual role, protecting against apneas while also amplifying CO2 responsiveness. The findings highlight peripheral chemoreceptors as a potential target for sex-specific therapies.
Source. Davaanyam D, et al. “Sex Differences in the Sleep Architecture and Sleep-Disordered Breathing in C57BL/6J Mice.” Sleep, published online ahead of print, June 27, 2026. PMID: 42364162. DOI: 10.1093/sleep/zsag176.