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Updated: Jun 18, 2026

Chronic Sleep Deprivation in Mouse Pups by Means of Gentle Handling
Published on: October 11, 2018
Biochemical, biometrical and behavioral changes in male offspring of sleep-deprived mice
Bruno Frederico Aguilar Calegare1, Leandro Fernandes, Sergio Tufik
1Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil.
Insights
Prenatal sleep deprivation in mice during early development impacts offspring physiology and behavior. This study reveals lasting effects on oxidative stress and tissue weight, highlighting potential epigenetic influences.
Area of Science:
- Neuroscience
- Developmental Biology
- Reproductive Science
Background:
- Prenatal exposure to adverse conditions is linked to cognitive and social deficits in offspring.
- Understanding the impact of specific prenatal stressors, like sleep deprivation, is crucial for developmental health.
Purpose of the Study:
- To investigate the long-term physiological and behavioral effects of sleep deprivation during the pre-implantation stage on adult male mouse offspring.
- To assess hormonal, biochemical, and oxidative stress markers in both dams and offspring.
Main Methods:
- Maternal sleep deprivation using platform (PSD 72) or gentle handling (GH 1, GH 2, GH 3) during early gestation.
- Measurement of maternal hormones (homocysteine, corticosterone, estrogen, progesterone) and offspring growth parameters.
- Assessment of offspring behavior (Activity Box, Elevated Plus Maze) and biochemical markers (superoxide dismutase) at postnatal day 90.
Main Results:
- Sleep deprivation altered maternal hormone levels, including decreased progesterone (PSD 72) and increased estradiol (GH 2).
- Offspring exhibited lasting impacts, such as reduced superoxide dismutase activity (GH 1) and decreased epididymal fat weight (PSD 72).
- Maternal hormonal changes were not the sole cause of offspring alterations; homocysteine changes may influence epigenetic development.
Conclusions:
- Prenatal sleep deprivation during the pre-implantation stage induces persistent physiological and metabolic alterations in adult male offspring.
- Homocysteine alterations in dams may play a role in redox changes and epigenetic modifications affecting offspring development.
- This research underscores the critical vulnerability of early developmental stages to maternal stress, with potential implications for neurodevelopmental disorders.
Abstract:
Epidemiological and experimental studies suggest a high prevalence of cognitive impairment and social behavior deficits in adolescents and adults that have experienced prenatal exposure to adverse conditions. This study investigated whether sleep deprivation during the pre-implantation stage of development alters the physiological, behavioral and oxidative metabolic processes in adult male mouse offspring. One group of dams was continuously sleep-deprived using the platform technique from gestational days 0 to 3 (PSD 72). Three additional groups were sleep-deprived by gentle handling for 6h on gestational days 1 (GH 1), 2 (GH 2) or 3 (GH 3). After sleep deprivation, homocysteine, cysteine, corticosterone, estrogen and progesterone concentrations were measured from the experimental mothers and time-matched controls. The sizes and weights of the male pups were measured at various stages throughout the experiment. At PND 90, behavioral (Activity Box and Elevated Plus Maze) and biochemical parameters were assessed. The dams' plasma progesterone concentrations decreased in the PSD 72 group, and the levels of plasma estradiol increased in GH 2. Corticosterone levels were found to increase after all sleep-deprivation procedures. Homocysteine concentrations increased in the GH 2 but decreased in the PSD 72 group. The offspring of GH 1 mothers exhibited decreased superoxide dismutase activity. Exposure to sleep deprivation had a long-lasting impact on tissue weight; in particular, there was a decrease in hemilateral epididymal fat weight in mature animals from the PSD 72 group. Although some of the alterations observed in the mothers (elevated estrogen and corticosterone levels and decreased progesterone) might have played a role in the permanent alterations in the adult offspring, they were not the main cause. The homocysteine changes detected in the sleep-deprived dams may contribute to redox changes, controlling gene expression and shaping epigenetic development.

