Gestational Chronodisruption Impairs Circadian Physiology in Rat Male Offspring, Increasing the Risk of Chronic Disease
Gestational Chronodisruption Impairs Circadian Physiology in Rat Male Offspring, Increasing the Risk of Chronic Disease
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DOI：
10.1210/en.2016-1282
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发表时间：
2016-12-01
期刊：
影响因子：
4.8
通讯作者：
Torres-Farfan, Claudia
中科院分区：
文献类型：
--
作者：
Mendez, Natalia;Halabi, Diego;Torres-Farfan, Claudia
在夜间长期暴露于光线下，如轮班工作，会改变生物钟（时间中断），对人类的怀孕产生负面影响。事实上，母亲和胎儿昼夜节律系统的相互作用可能是决定成年人健康状况的关键因素。我们认为，慢性光周期转换（CPS）在怀孕期间改变母亲的昼夜节律和损害昼夜生理在成年后代，增加健康风险。将妊娠大鼠暴露于正常光周期（12小时光照，12小时黑暗）或CPS，直到妊娠的85%。评估了妊娠期CPS对母亲和成年后代的影响。在母亲中，我们测量了心率，体温和活动的节律，通过妊娠和血浆变量（褪黑激素，皮质酮，醛固酮和肾功能标志物）在妊娠18天的每日节律。在成年后代中，我们测量了视交叉上核（SCN）中时钟基因表达的节律、自发活动、体温、心率、血压、血浆变量、葡萄糖耐量和皮质酮对ACTH的反应。CPS改变了所有母亲的昼夜节律，延长了妊娠期，并增加了新生儿体重。成年CPS后代呈现SCN中时钟基因表达的正常节律、运动活动和体温。然而，血浆褪黑激素的日节律是不存在的，皮质酮，醛固酮，肾脏标志物，血压和心率的节奏被改变。此外，CPS后代表现出葡萄糖耐量降低和对ACTH的异常皮质酮反应。总之，这些数据表明，妊娠期CPS诱导对后代昼夜节律系统的长期影响，其中正常的SCN与改变的内分泌、心血管和代谢功能共存。
Chronic exposure to light at night, as in shift work, alters biological clocks (chronodisruption), negatively impacting pregnancy out come in humans. Actually the interaction of maternal and fetal circadian systems could be a key factor determining a fitting health in adults. We propose that chronic photoperiod shift (CPS) during pregnancy alter maternal circadian rhythms and impair circadian physiology in the adult offspring, increasing health risks. Pregnant rats were exposed to normal photoperiod (12 h light, 12 h dark) or to CPS until 85% of gestation. The effects of gestational CPS were evaluated on the mother and adult offspring. In the mother we measured rhythms of heart rate, body temperature, and activity through gestation and daily rhythms of plasma variables (melatonin, corticosterone, aldosterone, and markers of renal function) at 18 days of gestation. In adult offspring, we measured rhythms of the clock gene expression in the supra-chiasmatic nucleus (SCN), locomotor activity, body temperature, heart rate, blood pressure, plasma variables, glucose tolerance, and corticosterone response to ACTH. CPS altered all maternal circadian rhythms, lengthened gestation, and increased newborn weight. The adult CPS offspring presented normal rhythms of clock gene expression in the SCN, locomotor activity, and body temperature. However, the daily rhythm of plasma melatonin was absent, and corticosterone, aldosterone, renal markers, blood pressure, and heart rate rhythms were altered. Moreover, CPS offspring presented decreased glucose tolerance and an abnormal corticosterone response to ACTH. Altogether these data show that gestational CPS induced long-term effects on the offspring circadian system, wherein a normal SCN coexists with altered endocrine, cardiovascular, and metabolic function.