Effect of estrogens on sex-specific influence in sleep deprivation in mice

Men and women generally exhibit different sleep patterns and structures. These differences also extend to how each sex responds to sleep deprivation, a condition linked to various health issues. Although estradiol is known to influence sleep patterns, its sex-specific effects on sleep characteristics and the responses to sleep deprivation are not well understood. In our study, we used a genetic estrogen deficiency mouse model with aromatase deficiency (Ar^+/-) to explore estrogens' sex-specific role in reactions to acute sleep deprivation (SD). Initially, we identified a sex difference in SD-induced sleep-wake proportions and sleep patterns in wild type (WT) mice. Then, we found that estrogens deficiency caused alterations of normal sleep pattern in females, characterized by less wakefulness and more NREM time, but not in males at baseline compared to WT mice. While SD led to significant alterations in circadian rhythm, sleep patterns, and sleep rebound in both male and female Ar^+/- mice, sex differences were evident in specific responses to SD. Female Ar^+/- mice exhibited a quicker and longer-lasting post-SD sleep rebound, with reduced wake time, increased sleep time, and less fragmented sleep, whereas male Ar^+/- mice showed a delayed sleep rebound except for REM sleep time and REM sleep spectral alterations compared to WT mice. Our findings underscore the crucial role of endogenous estrogens in sleep regulation and its sex-specific response to sleep deprivation, which could be significant for precision sleep medicine.