Endocrine Abstracts

Disruption of circadian regulation could trigger and exacerbate obesity, type 2 diabetes mellitus, and cardiovascular disease. Experiments on rats proved that the deleterious effects of chronodisruption are extremely severe, especially during early developmental stages. Only part of them could be prevented by maternal melatonin administration, suggesting that other pathophysiological mechanisms may be involved. To investigate the role of other mechanisms that might contribute to communication between the maternal and fetal circadian systems, we used PER2::LUC knock-in mice (original strain C57BL), which naturally lack melatonin. The mice carry a PER2 protein fused to luciferase, allowing for the monitoring of clock function ex vivo. Pregnant dams were exposed to either standard light conditions (LD12:12) or constant light (LL) from the first day of gestation (G0.5). Samples were collected at G17.5. Fetuses of both sexes had higher body weights in the LL group already at G17.5. Interestingly, clock function in the peripheral oscillators was impaired, with females being more affected than males. In addition, we found that clock function in the placenta and expression of the glucocorticoid-converting enzymes Hsd11b1 and Hsd11b2 were affected by maternal chronodisruption. To investigate the temporal character of the alterations, we collected samples from adult animals born to LL or LD-exposed mothers. Metabolomic analysis revealed that females born to LL-exposed mothers still differed from the control animals even in adulthood. Our data show that maternal chronodisruption affects the clock in various fetal tissues and organs of mice via melatonin-independent pathways and affects metabolism in a sex-dependent manner. The obtained results emphasize the adverse effects of artificial light during the subjective night for pregnant women.