Stage-Specific Effects of Maternal Circadian Rhythm Disruption during Pre-Pregnancy, Pregnancy, and Lactation on...

Maternal circadian rhythm disruption (CRD) during reproduction is increasingly recognized as a risk factor for long-term neurobehavioral disturbances in offspring. However, the stage-specific consequences of maternal CRD remain poorly understood. This study investigated the effects of maternal CRD during distinct reproductive phases, pre pregnancy mother (PPM), pregnancy mother (PM), and lactationg mother (LM) on behavioral and molecular, and structural outcomes in male offspring. Nulliparous Wistar rats were exposed to constant light (300 lx, 14 days) to induce CRD, while controls remained on a 12:12 h light/dark cycle. Male offspring were assessed for anxiety-like behavior (Elevated Plus Maze), depressive-like behavior (Forced Swim Test), hedonic behavior (Sucrose Preference Test), compulsive-like behavior (Marble Burying Test), and recognition memory (Novel Object Recognition Test). Histological analysis of the hippocampal CA1 region and expression of Brain-Derived Neurotrophic Factor (BDNF) and PER2 were also evaluated. PPM and PM offspring exhibited increased anxiety- and depressive-like behaviors, reduced body weight, alterations in hippocampal CA1 morphology, and molecular changes, including decreased hippocampal BDNF expression in the PM group and reduced SCN PER2 expression in the PPM group, without significant impairments in hedonic or recognition memory performance. In contrast, LM offspring exhibited fewer behavioral alterations compared with the other experimental groups, suggesting a differential effect of the timing of maternal circadian rhythm disruption on offspring outcomes. Considering the functional and neurodevelopmental similarities between late gestation in humans and early postnatal development in rodents, these findings suggest that the timing of maternal circadian rhythm disruption may differentially influence offspring neurodevelopment. However, because these observations were obtained in an animal model, their relevance to human pregnancy should be interpreted with caution and requires confirmation in future clinical and translational studies.