Association of Maternal Preconception Chronodisruption and Oocyte m6A Modification with Multi-Organ Phenotypic Alterations in Offspring
Renke He, Kejing Zhu, Zhaoying Jiang, Jiaen Yu, Haiyan Wu, Qinyu Luo, Tianxin Zhao, Liandong Zuo, Zhongzhong Chen, Hefeng HuangWhile the natural light–dark cycle is crucial for health, modern lifestyles are associated with increased artificial light exposure, including during reproductive windows. Although maternal light exposure has been linked to adverse offspring outcomes, comprehensive multisystem evaluations remain scarce. In this study, we established a rat model of continuous light exposure to simulate maternal preconception chronodisruption. We found that preconception chronodisruption was associated with multisystem abnormalities in offspring, including increased body weight, diminished cardiac function, thickened vessel walls, elevated blood pressure, and insulin resistance. Behavioral tests revealed stress-coping and behavioral despair-related responses along with impaired cognitive function. The m6A methylation patterns in maternal oocytes were altered and enriched in developmental pathways related to the brain, muscle, and cardiovascular systems. Collectively, preconception exposure to continuous light was associated with physiological and behavioral deficits in offspring, and these deficits were potentially related to m6A RNA modification changes in maternal oocytes. These findings underscore the importance of preconception environmental factors and suggest a potential link between oocyte epigenetics and developmental programming.