School of Anatomy and Human Biology, The University of Western Australia, 35 Stirling Highway, Nedlands, Western Australia, Australia.
Endocrinology. 2011 Sep;152(9):3552-60. doi: 10.1210/en.2011-0081. Epub 2011 Jul 19.
Clock genes drive circadian rhythms in a range of physiological processes both centrally and in peripheral tissues such as the liver. The aims of this study were to determine whether the two functionally-distinct zones of the rat placenta (junctional and labyrinth) differentially express clock genes and, if so, whether these exhibit circadian patterns. Rats were sampled from d 21 of pregnancy (term = d 23) and from diestrus I of the estrous cycle. Adult liver (all animals), fetal liver, and placental zones (pregnant animals) were collected at 0800, 1400, 2000, and 0200 h. Both zones of the rat placenta expressed all seven canonical clock genes (Clock, Bmal1, Per1, Per2, Per3, Cry1, and Cry2), but there were marked zonal differences and, unlike in maternal liver, circadian variation in placenta was limited. Similarly, placental expression of Vegf varied with zone but not time of day. Pregnancy also led to marked changes in hepatic clock gene expression, with peak levels of Per1, Cry1, and Cry2 all reduced, Per3 increased, and circadian variation in Clock expression lost. All clock genes were expressed in fetal liver, but there was less circadian variation than in maternal liver. Similarly, fetal corticosterone levels remained stable across the day, whereas maternal corticosterone showed clear circadian variation. In conclusion, our data show that the rat placenta expresses all canonical clock genes in a highly zone-specific manner but with relatively little circadian variation. Moreover, pregnancy alters the expression and circadian variation of clock genes in maternal liver, possibly contributing to maternal physiological adaptations.
时钟基因在中枢和外周组织（如肝脏）的一系列生理过程中驱动昼夜节律。本研究旨在确定大鼠胎盘的两个功能不同的区域（连接区和绒毛膜区）是否差异表达时钟基因，如果是，这些基因是否表现出昼夜节律模式。从妊娠第 21 天（足月为第 23 天）和发情周期的第 1 天（动情前期）采集大鼠样本。在 0800、1400、2000 和 0200 h 时收集成年肝脏（所有动物）、胎儿肝脏和胎盘区域（妊娠动物）。大鼠胎盘的两个区域均表达所有 7 个经典时钟基因（Clock、Bmal1、Per1、Per2、Per3、Cry1 和 Cry2），但存在明显的区域差异，与母鼠肝脏不同，胎盘的昼夜节律变化有限。同样，胎盘 Vegf 的表达也随区域而异，而不是随时间变化。妊娠还导致肝时钟基因表达发生明显变化，Per1、Cry1 和 Cry2 的峰值水平降低，Per3 增加，Clock 表达的昼夜节律变化消失。所有时钟基因在胎肝中均有表达，但昼夜变化比母鼠肝脏少。同样，胎儿皮质酮水平全天保持稳定，而母鼠皮质酮则表现出明显的昼夜节律变化。总之，我们的数据表明，大鼠胎盘以高度区域特异性的方式表达所有经典时钟基因，但昼夜变化相对较小。此外，妊娠改变了母鼠肝脏中时钟基因的表达和昼夜节律变化，可能有助于母体的生理适应。
