Effects of exposure to low-level artificial light at night and melatonin supplementation on maternal‑fetal outcomes in pregnant mice: Insights from placental and decidual pathways

Exposure to low-level artificial-light at night (L-ALAN) during pregnancy is increasingly common and disrupt melatonin (MT) synthesis. MT maintains circadian rhythm homeostasis and placental/decidual functions. This study aimed to investigate the effects of prenatal L-ALAN exposure and MT intervention on maternal–fetal outcomes and underlying mechanisms. Pregnant C57BL/6 J mice were exposed to L-ALAN (2 lx during night) with or without MT supplementation (10 mg/kg/day, intragastrically) and assessed at embryonic day 16.5 or after natural delivery. Maternal serum and placental MT levels, and related maternal–fetal outcomes were evaluated. Morphological, circadian-omics, and RT-qPCR analyses were conducted to evaluate structural and functional changes in the maternal-placenta-decidual-fetal tissues. Circadian rhythmicity of core-circadian-clock-genes was evaluated using Jonckheere-Terpstra-Kendall (JTK)-CYCLE analysis. L-ALAN reduced nocturnal maternal serum and placental MT peaks, gestational-weight-gains, P4/E2 ratio, maternal liver and spleen indices, placental and fetal weights, and offspring survival. Placental and decidual structural and functional markers were also impaired. L-ALAN disrupted core-circadian-clock-gene expression and increased inflammatory cytokines in the maternal-placenta-decidual-fetal tissues. MT supplementation partially attenuated several of these alterations, whereas maternal organ indices, fetal weights, and fetal liver inflammatory responses were not significantly restored. Gestational L-ALAN exposure suppressed circulating and placental MT secretion, induced gestational hormonal and metabolic dysfunctions and decreased placental/fetal weights. Impaired maternal–fetal interface architecture and function, secondary to circadian rhythm disturbances and inflammatory activation, underlies these detrimental effects, while MT supplementation partially attenuated selected L-ALAN-associated alterations. As the C57BL/6 J strain exhibits deficient pineal MT synthesis, these findings primarily reflect alterations in peripheral (circulating and placental) MT availability.