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Females Experience Less Restorative Sleep Than Males in Mouse Study

A girl sleeping in bed.
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A recent study by researchers at the University of Colorado Boulder has found significant differences in sleep behavior between male and female mice. Male mice slept longer and experienced more restorative sleep compared to females. These findings, published in Scientific Reports, highlight the importance of accounting for sex-based differences in biomedical research.


The study utilized 267 C57BL/6J mice, a strain commonly used in research, to assess sleep behaviors. Male mice averaged 670 minutes of sleep per 24-hour cycle – an hour longer than females. This additional rest primarily occurred during non-Rapid Eye Movement (NREM) sleep, which is critical for cellular repair and recovery.


Non-Rapid Eye Movement (NREM) sleep

NREM sleep is a restorative stage of the sleep cycle characterized by slower brain waves, reduced heart rate, and lower blood pressure. It is essential for tissue repair and immune system strengthening.


Female mice, in contrast, exhibited more fragmented sleep, characterized by shorter bouts of rest and frequent awakenings. These patterns are consistent with behaviors observed in other species, including birds and zebrafish, suggesting a possible evolutionary role tied to caregiving behaviors.

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Biological factors influencing sleep differences

Researchers propose that hormonal differences, including variations in stress hormones like cortisol and reproductive hormones such as estrogen and progesterone, contribute to the observed disparities. For instance, during phases of the menstrual cycle where estrogen and progesterone levels are low, women also report poorer sleep quality, mirroring patterns seen in female mice.


Cortisol

Cortisol is a hormone produced by the adrenal glands, playing a key role in stress response, metabolism, and wakefulness regulation. Elevated levels are often associated with disrupted sleep.


The study challenges the hypothesis that females inherently need less sleep, suggesting instead that societal pressures and stress may exacerbate perceptions of poor sleep.

Implications for biomedical research

Sex bias in animal studies remains a significant concern, despite the National Institutes of Health’s 2016 mandate to include sex as a biological variable. The findings emphasize the need for balanced representation in research populations. Simulations conducted as part of the study revealed that treatments appearing ineffective in unbalanced male-dominant samples might work optimally in females if appropriately studied.


Failure to account for sex differences could lead to flawed conclusions, potentially delaying drug development and obscuring side effects that disproportionately impact one sex.

Next steps for research

The researchers advocate for greater inclusion of both sexes in animal studies and encourage re-evaluation of previous findings that may have underrepresented females. By ensuring a balanced approach, scientists can improve the translatability of animal research to human clinical trials, accelerating the development of effective treatments.


Reference: Mannino GS, Green TRF, Murphy SM, Donohue KD, Opp MR, Rowe RK. The importance of including both sexes in preclinical sleep studies and analyses. Sci Rep. 2024;14(1):23622. doi: 10.1038/s41598-024-70996-1


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