Data_Sheet_2_Long-Term Effects of Altered Photoperiod During Pregnancy on Liver Gene Expression of the Progeny.xlsx

Experimental and epidemiological studies have revealed a relationship between an adverse intrauterine environment and chronic non-communicable disease (NCD) like cardiovascular disease (CVD) in adulthood. An important risk factor for CVD is the deregulation of the fibrinolytic system particularly high levels of expression of plasminogen activator inhibitor 1 (Pai-1). Chronic exposure to altered photoperiod disrupts the circadian organization of physiology in the pregnant female, known as gestational chronodisruption, and cause long-term effects on the adult offspring’s circadian physiology. The Pai-1 expression is regulated by the molecular components of the circadian system, termed clock genes. The present study aimed to evaluate the long-term effects of chronic photoperiod shifts (CPS) during pregnancy on the expression of the clock genes and the fibrinolytic system in the liver of adult male offspring. Our results using an animal model demonstrated statistically significant differences at the transcriptional level in males gestated under CPS. At 90 days of postnatal age, the liver transcript levels of the clock gene Bmal1 were downregulated, whereas Rorα, Rorγ, Nfil3, and Pai-1 were upregulated. Our data indicate that CPS during pregnancy affects gene expression in the liver of male adult progeny, showing that alteration of the photoperiod in the mother’s environment leads to persistent effects in the offspring. In conclusion, these results reveal for the first time the long-term effects of gestational chronodisruption on the transcriptional activity of one well-established risk factor associated with CVD in the adult male offspring.

实验与流行病学研究已证实，不良宫内环境（intrauterine environment）与成年期慢性非传染性疾病（chronic non-communicable disease, NCD）——如心血管疾病（cardiovascular disease, CVD）——存在关联。心血管疾病的重要危险因素之一为纤溶系统（fibrinolytic system）功能失调，尤以纤溶酶原激活物抑制剂1（plasminogen activator inhibitor 1, Pai-1）的表达水平升高最为显著。长期暴露于改变的光周期（photoperiod）会扰乱妊娠母体的生理昼夜节律调控，该现象被称为妊娠节律紊乱（gestational chronodisruption），并会对成年子代的昼夜节律生理产生长期影响。纤溶酶原激活物抑制剂1（Pai-1）的表达受昼夜节律系统的分子组分——时钟基因（clock genes）——调控。本研究旨在评估妊娠期间慢性光周期偏移（chronic photoperiod shifts, CPS）对成年雄性子代肝脏中时钟基因及纤溶系统表达的长期影响。本研究采用动物模型开展实验，结果显示，在慢性光周期偏移环境下孕育的雄性子代，其肝脏组织的转录水平存在具有统计学意义的显著差异。在出生后90日龄时，时钟基因Bmal1的肝脏转录本水平呈下调状态，而Rorα、Rorγ、Nfil3及Pai-1的转录本水平则显著上调。本研究数据表明，妊娠期间的慢性光周期偏移会改变雄性成年子代的肝脏基因表达模式，证实母体环境的光周期改变会对子代产生持续性影响。综上，本研究首次揭示了妊娠节律紊乱对成年雄性子代心血管疾病相关明确危险因素的转录活性产生的长期影响。