The Role of Reproductive Hormones in Sex Differences in Sleep Homeostasis and Arousal Response in Mice

Abstract

There are various sex differences in sleep/wake behaviors in mice. However, it is unclear whether there are sex differences in sleep homeostasis and arousal responses and whether gonadal hormones are involved in these sex differences. Here, we examined sleep/wake behaviors under baseline condition, after sleep deprivation by gentle handling, and arousal responses to repeated cage changes in male and female C57BL/6 mice that are hormonally intact, gonadectomized, or gonadectomized with hormone supplementation. Compared to males, females had longer wake time, shorter non-rapid eye movement sleep (NREMS) time, and longer rapid eye movement sleep (REMS) episodes. After sleep deprivation, males showed an increase in NREMS delta power, NREMS time, and REMS time, but females showed a smaller increase. Females and males showed similar arousal responses. Gonadectomy had only a modest effect on homeostatic sleep regulation in males but enhanced it in females. Gonadectomy weakened arousal response in males and females. With hormone replacement, baseline sleep in gonadectomized females was similar to that of intact females, and baseline sleep in gonadectomized males was close to that of intact males. Gonadal hormone supplementation restored arousal response in males but not in females. These results indicate that male and female mice differ in their baseline sleep–wake behavior, homeostatic sleep regulation, and arousal responses to external stimuli, which are differentially affected by reproductive hormones.

Probing different paradigms of morphine withdrawal on sleep behavior in male and female C57BL/6J mice

“…1). Similar to other reports in rodents [38], we saw that male and female C57BL/6J mice sleep differently at baseline, with the males sleeping on average 58.3% of the light cycle and 22.9% of the dark cycle while females slept 52.0% of the light cycle and 22.6% of the dark cycle (Fig. 2).…”

“…Previous studies have found differences in baseline sleep between male and female mice [38], we confirmed similar sex differences here using our sleep measurements with the PiezoSleep system. We found a main effect of sex on % time asleep in the light cycle (Figure 2A, F(1,102) =30.62, p<0.0001), and a significant interaction of sex vs. time (Fig.…”

Mice Lacking Cerebellar Cortex and Related Structures Show a Decrease in Slow-Wave Activity With Normal Non-REM Sleep Amount and Sleep Homeostasis

“…There are several limitations to this study. Although male mice were used in this study to reduce the number of mice, female Ptf1a cKO mice may yield different results, as we have showed that the sleep/wake behavior of female mice differs from that of male mice (Choi et al, 2021 ). Compensation for the loss of the cerebellum from the embryonic stage may have weakened the sleep phenotype of Ptf1a cKO mice.…”

Hunt for mammalian sleep-regulating genes

“…If they showed the same sleep abnormalities as their father F1 mouse, these mice were further used for quantitative trait locus analysis and whole-exome sequencing. Because of the large difference in sleep between males and females, only male mice were used for sleep analysis [30]. This approach identified the genetic mutations responsible for heritable sleep abnormalities, such as the Sik3 gene mutation in the Sleepy mutant pedigree and the Nalcn gene mutation in the Dreamless mutant pedigree [31] (Fig.…”