Maternal circadian disruption during pregnancy and offspring diabetic cardiovascular disease risk

Abstract

Circadian rhythm disruption during pregnancy has been recognized as a growing public health concern, affecting approximately 20% of the workforce due to shift work and prevalent lifestyle-related factors. Grounded in the developmental origins of health and disease (DOHaD) paradigm, emerging evidence indicates that maternal circadian disruption (MCD) may have profound transgenerational effects, programming offspring susceptibility to diabetes mellitus and its cardiovascular complications. This narrative review synthesizes current mechanistic evidence linking MCD to offspring cardiometabolic disease (CMD), emphasizing the integrated clock-metabolic-oxidative stress axis. Disruption of core clock genes, including CLOCK, BMAL1, and CRY/PER, lead to impaired glucose homeostasis, mitochondrial function, and antioxidant defense, subsequently promoting generation of reactive oxygen species (ROS) and exacerbating oxidative stress. These disturbances contribute to endothelial dysfunction, vascular inflammation, and accelerated atherogenesis in offspring. Chronotherapeutic approaches, particularly melatonin supplementation and circadian-aligned lifestyle modifications, represent promising strategies in mitigating these programmed deficits. Elucidating this clock-metabolic-oxidative stress axis will provide essential insights to develop preventive and therapeutic interventions to address the developmental origins of CMD across generations.