Bebas Piotr, Goodall Cheri P, Majewska Magda, Neumann Adam, Giebultowicz Jadwiga M, Chappell Patrick E
Department of Animal Physiology, Faculty of Biology, University of Warsaw, Warsaw, Poland.
FASEB J. 2009 Feb;23(2):523-33. doi: 10.1096/fj.08-113191. Epub 2008 Oct 22.
Circadian clocks regulate multiple rhythms in mammalian tissues. In most organs core clock gene expression is oscillatory, with negative components Per and Cry peaking in antiphase to Bmal1. A notable exception is the testis, where clock genes seem nonrhythmic. Earlier mammalian studies, however, did not examine clock expression patterns in accessory ductal tissue required for sperm maturation and transport. Previous studies in insects demonstrated control of sperm maturation in vas deferens by a local circadian system. Sperm ducts express clock genes and display circadian pH changes controlled by vacuolar-type H(+)-ATPase and carbonic anhydrase (CA-II). It is unknown whether sperm-processing rhythms are conserved beyond insects. To address this question in mice housed in a light-dark environment, we examined temporal patterns of mPer1 and Bmal1 gene expression and protein abundance in epididymis, vas deferens, seminal vesicles, and prostate. Results demonstrate variable tissue-specific patterns of expression of the two genes, with variations in levels of clock proteins and their nucleo-cytoplasmic cycling observed among examined tissues. Strikingly, mPer1 and Bmal1 mRNA and proteins oscillate in antiphase in the prostate, with similar peak-trough patterns as observed in the suprachiasmatic nuclei, the brain's central clock. Genes encoding CA and a V-ATPase subunit, which are rhythmically expressed in sperm ducts of moths, are also rhythmic in some segments of murine sperm ducts. Our data suggest that some sperm duct segments may contain peripheral circadian systems whereas others may express clock genes in a pleiotropic manner.
昼夜节律时钟调节哺乳动物组织中的多种节律。在大多数器官中,核心时钟基因的表达是振荡性的,其中负调控成分Per和Cry的峰值与Bmal1呈反相。一个显著的例外是睾丸,其中时钟基因似乎没有节律。然而,早期的哺乳动物研究并未检查精子成熟和运输所需的附属导管组织中的时钟表达模式。先前对昆虫的研究表明,输精管中的局部昼夜节律系统可控制精子成熟。精子导管表达时钟基因,并表现出由液泡型H(+)-ATP酶和碳酸酐酶(CA-II)控制的昼夜pH变化。精子处理节律是否在昆虫之外保守尚不清楚。为了在明暗环境饲养的小鼠中解决这个问题,我们检查了附睾、输精管、精囊和前列腺中mPer1和Bmal1基因表达以及蛋白质丰度的时间模式。结果表明这两个基因存在可变的组织特异性表达模式,在所检查的组织中观察到时钟蛋白水平及其核质循环的变化。引人注目的是,mPer1和Bmal1的mRNA和蛋白质在前列腺中呈反相振荡,其峰谷模式与大脑的中央时钟视交叉上核中观察到的相似。在蛾类精子导管中有节律表达的编码CA和V-ATP酶亚基的基因,在小鼠精子导管的某些节段中也有节律。我们的数据表明,一些精子导管节段可能包含外周昼夜节律系统,而其他节段可能以多效性方式表达时钟基因。