Circadian clocks during embryonic and fetal development

Abstract

Circadian rhythmicity is a fundamental characteristic of organisms, which helps ensure that vital functions occur in an appropriate and precise temporal sequence and in accordance with cyclic environmental changes. Living beings are endowed with a system of biological clocks that measure time on a 24-hr basis, termed the circadian timing system. In mammals, the system is organized as a master clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus, commanding peripheral clocks located in almost every tissue of the body. At the cell level, interlocking transcription/translation feedback loops of the genes Bmal-1, Clock, Per1-2, and Cry1-2, named clock genes, and their protein products results in circadian oscillation of clock genes and of genes involved in almost every cellular function. During gestation, the conceptus follows a complex and dynamic program by which it is simultaneously fit to develop and live in a circadian environment provided by its mother and to prepare for the very different environment that it will experience after birth. It has been known for a number of years that the mother tells the fetus the time of day and season of the year, and that the fetus uses this information to set the phase of fetal and neonatal circadian rhythms. There is evidence that the maternal rhythm of melatonin is one of the time signals to the fetus. In the last few years, the study of the development of the circadian system has turned to the investigation of the oscillatory expression of clock genes and their possible role in development, and to answering questions on the organization of the fetal circadian system. Emerging evidence shows that clock genes are expressed in the oocyte and during early and late development in embryo/fetal organs in the rat and in a fetal primate. The data available raise the intriguing possibility that the fetal SCN and fetal tissues may be peripheral clocks commanded by separate maternal signals. The rapid methodological and conceptual advances on chronobiology may help to unravel how the developing embryo and fetus faces time in this plastic period of life.