Circadian rhythms in the fetus

Abstract

Throughout gestation, the close relationship between mothers and their progeny ensures adequate development and a successful transition to postnatal life. By living inside the maternal compartment, the fetus is inevitably exposed to rhythms of the maternal internal milieu such as temperature; rhythms originated by maternal food intake and maternal melatonin, one of the few maternal hormones that cross the placenta unaltered. The fetus, immature by adult standards, is however perfectly fit to accomplish the dual functions of living in the uterine environment and developing the necessary tools to “mature” for the next step, i.e. to be a competent newborn. In the fetal physiological context, organ function differs from the same organ’s function in the newborn and adult. This may also extend to the developing circadian system. The information reviewed here suggests that the fetal circadian system is organized differently from that of the adult. Moreover, the fetal circadian rhythm is not just present simply as the initial immature expression of a mechanism that has function in the postnatal animal only. We propose that the fetal suprachiasmatic nucleus (SCN) of the hypothalamus and fetal organs are peripheral maternal circadian oscillators, entrained by different maternal signals. Conceptually, the arrangement produces internal temporal order during fetal life, inside the maternal compartment. Following birth, it will allow for postnatal integration of the scattered fetal circadian clocks into an adult-like circadian system commanded by the SCN.

Introduction

The Child is father of the Man

From “My heart leaps up when I behold”;

William Wordsworth, 1802

Wordsworth verses are very relevant for the fetal and neonatal physiologist, given the evidence that situations encountered in utero have long lasting consequences in adult life, known as programming. Throughout gestation, the close relationship between mothers and their progeny ensures adequate development and a successful transition to the postnatal life. The mother supplies oxygen, nutrients and hormones. The placenta, contributes to, regulates and also determines the rate of exchange of the above substrates. By living inside the maternal compartment, the fetus is unavoidably exposed to rhythms of the maternal internal milieu such as temperature, rhythms originated by maternal food intake and maternal melatonin, one of the few maternal hormones that cross the placenta unaltered. Even the effects of gravitation are decreased during gestation. The fetal-maternal arrangement changes abruptly at delivery. The newborn now depends on maternal behavior for care and feeding (and its own capacity to trigger appropriate maternal behavior). In addition it is left without a warm environment and without maternal hormones like melatonin and placental hormones.

An important consideration in trying to understand the fetal circadian system is that the fetus is not just a small and immature adult living inside a compartment provided by the mother. The fetus, is perfectly fit to accomplish the dual functions of living in the uterine environment while developing the necessary tools to “mature” into a competent newborn. A feat performed by the fetus is to live in a low PO₂ environment at a high external temperature. In such physiological context, fetal organs function differs from the same organ’s function in the newborn and adult. Examples are seen in the cardiorespiratory system, (heart and lung), kidney, brown adipose tissue, liver and pineal gland among others. This may extend to the developing circadian system. The information to be reviewed here suggests that the fetal circadian system may be of functional significance for the fetus and not just present simply as the initial expression of a mechanism that has functions only in the postnatal animal.