Abstract
Timing of balanced and precise daily delivery of oxygen, nutrients, hormones, and biophysical cues from mother to fetus is essential for fetal growth and successful transition to extrauterine life. Such timing is provided by an arrangement of biological clocks operating in the mother and fetus. However, adverse intrauterine conditions including effects of altering the photoperiod (chronodisruption) during gestation on fetal growth/development and postnatal physiology may translate into adult disease, in which the role played by fetal circadian system remains unclear. Here we review the development of the circadian system, changes experienced by the maternal circadian system during pregnancy, evidence that chronodisruption during pregnancy has long-term effects on the offspring, and current experimental approaches utilized to investigate these issues. However, we are aware that we are just now obtaining new pieces of information that needs to be broadened and studied searching for a diurnal model more comparable to humans. Physiological and pathophysiological questions related to the mother-fetus pair and neonate in vivo need to be addressed as well as the corresponding consequences in adulthood, with expanded and new techniques: among the latter, effects on the transcriptome, microRNA regulome (miRNome), and proteome of different maternal-fetal, neonatal, and adult tissues.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Erren TC, Reiter RJ (2009) Defining chronodisruption. J Pineal Res 46:245–247
Bass J, Takahashi JS (2010) Circadian integration of metabolism and energetics. Science 330:1349–1354
Reppert SM, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418:935–941
Richter HG, Torres-Farfan C, Rojas-Garcia PP, Campino C, Torrealba F, Seron-Ferre M (2004) The circadian timing system: making sense of day/night gene expression. Biol Res 37:11–28
Ishida A, Mutoh T, Ueyama T, Bando H, Masubuchi S, Nakahara D, Tsujimoto G, Okamura H (2005) Light activates the adrenal gland: timing of gene expression and glucocorticoid release. Cell Metab 2:297–307
Watanabe T et al (2006) Peripheral clock gene expression in CS mice with bimodal locomotor rhythms. Neurosci Res 54:295–301
Fustin JM, Dardente H, Wagner GC, Carter DA, Johnston JD, Lincoln GA, Hazlerigg DG (2009) Egr1 involvement in evening gene regulation by melatonin. FASEB J 23:764–773
Levi F, Schibler U (2007) Circadian rhythms: mechanisms and therapeutic implications. Annu Rev Pharmacol Toxicol 47:593–628
Resuehr HE, Resuehr D, Olcese J (2009) Induction of mPer1 expression by GnRH in pituitary gonadotrope cells involves EGR-1. Mol Cell Endocrinol 311:120–125
Sumova A, Bendova Z, Sladek M, El-Hennamy R, Mateju K, Polidarova L, Sosniyenko S, Illnerova H (2008) Circadian molecular clocks tick along ontogenesis. Physiol Res 57(Suppl 3):S139–S148
Jud C, Albrecht U (2006) Circadian rhythms in murine pups develop in absence of a functional maternal circadian clock. J Biol Rhythms 21:149–154
Seron-Ferre M et al (2012) Circadian rhythms in the fetus. Mol Cell Endocrinol 349:68–75
Davis FC, Reppert SM (2001) Development of mammalian circadian rhythms. In: Takahashi JS, Turek FW, Moore RY (eds) Circadian clocks, Handbooks of behavioral neurobiology. Kluwer Academic/Plenum Publishers, New York, NY, pp 247–291
Reppert SM, Schwartz WJ (1984) Functional activity of the suprachiasmatic nuclei in the fetal primate. Neurosci Lett 46:145–149
Reppert SM, Schwartz WJ (1983) Maternal coordination of the fetal biological clock in utero. Science 220:969–971
Davis FC, Gorski RA (1985) Development of hamster circadian rhythms. I. Within-litter synchrony of mother and pup activity rhythms at weaning. Biol Reprod 33:353–362
Novakova M, Sladek M, Sumova A (2010) Exposure of pregnant rats to restricted feeding schedule synchronizes the SCN clocks of their fetuses under constant light but not under a light-dark regime. J Biol Rhythms 25:350–360
Constandil L, Parraguez VH, Torrealba F, Valenzuela G, Seron-Ferre M (1995) Day-night changes in c-fos expression in the fetal sheep suprachiasmatic nucleus at late gestation. Reprod Fertil Dev 7:411–413
Breen S, Rees S, Walker D (1996) The development of diurnal rhythmicity in fetal suprachiasmatic neurons as demonstrated by fos immunohistochemistry. Neuroscience 74:917–926
Seron-Ferre M, Valenzuela GJ, Torres-Farfan C (2007) Circadian clocks during embryonic and fetal development. Birth Defects Res C Embryo Today 81:204–214
Torrealba F, Parraguez VH, Reyes T, Valenzuela G, Seron-Ferre M (1993) Prenatal development of the retinohypothalamic pathway and the suprachiasmatic nucleus in the sheep. J Comp Neurol 338:304–316
Muller C, Torrealba F (1998) Postnatal development of neuron number and connections in the suprachiasmatic nucleus of the hamster. Brain Res Dev Brain Res 110:203–213
Torres-Farfan C et al (2006) Maternal melatonin effects on clock gene expression in a nonhuman primate fetus. Endocrinology 147: 4618–4626
Bendova Z, Sumova A, Illnerova H (2004) Development of circadian rhythmicity and photoperiodic response in subdivisions of the rat suprachiasmatic nucleus. Brain Res Dev Brain Res 148:105–112
Ko MS et al (2000) Large-scale cDNA analysis reveals phased gene expression patterns during preimplantation mouse development. Development 127:1737–1749
Johnson MH, Lim A, Fernando D, Day ML (2002) Circadian clockwork genes are expressed in the reproductive tract and conceptus of the early pregnant mouse. Reprod Biomed Online 4:140–145
Saxena MT, Aton SJ, Hildebolt C, Prior JL, Abraham U, Piwnica-Worms D, Herzog ED (2007) Bioluminescence imaging of period1 gene expression in utero. Mol Imaging 6:68–72
Sladek M, Jindrakova Z, Bendova Z, Sumova A (2007) Postnatal ontogenesis of the circadian clock within the rat liver. Am J Physiol Regul Integr Comp Physiol 292:R1224–R1229
Torres-Farfan C, Mendez N, Abarzua-Catalan L, Vilches N, Valenzuela GJ, Seron-Ferre M (2011) A Circadian clock entrained by melatonin is ticking in the rat fetal adrenal. Endocrinology 152:1891–1900
Polidarova L, Olejnikova L, Pauslyova L, Sladek M, Sotak M, Pacha J, Sumova A (2014) Development and entrainment of the colonic circadian clock during ontogenesis. Am J Physiol Gastrointest Liver Physiol 306:G346–G356
Vilches N, Spichiger C, Mendez N, Abarzua-Catalan L, Galdames HA, Hazlerigg DG, Richter HG, Torres-Farfan C (2014) Gestational chronodisruption impairs hippocampal expression of NMDA receptor subunits Grin1b/Grin3a and spatial memory in the adult offspring. PLoS One 9:e91313
Meszaros K, Pruess L, Szabo AJ, Gondan M, Ritz E, Schaefer F (2014) Development of the circadian clockwork in the kidney. Kidney Int 86:915
Liggins GC (1994) The role of cortisol in preparing the fetus for birth. Reprod Fertil Dev 6:141–150
Underwood MA, Gilbert WM, Sherman MP (2005) Amniotic fluid: not just fetal urine anymore. J Perinatol 25:341–348
Nishide SY, Hashimoto K, Nishio T, Honma K, Honma S (2014) Organ-specific development characterizes circadian clock gene Per2 expression in rats. Am J Physiol Regul Integr Comp Physiol 306:R67–R74
Hiroshige T, Honma K, Watanabe K (1982) Ontogeny of the circadian rhythm of plasma corticosterone in blind infantile rats. J Physiol 325:493–506
Deguchi T (1975) Ontogenesis of a biological clock for serotonin:acetyl coenzyme A N-acetyltransferase in pineal gland of rat. Proc Natl Acad Sci U S A 72:2814–2818
Reppert SM, Schwartz WJ (1986) Maternal suprachiasmatic nuclei are necessary for maternal coordination of the developing circadian system. J Neurosci 6:2724–2729
Weaver DR, Reppert SM (1989) Periodic feeding of SCN-lesioned pregnant rats entrains the fetal biological clock. Brain Res Dev Brain Res 46:291–296
Okatani Y, Okamoto K, Hayashi K, Wakatsuki A, Tamura S, Sagara Y (1998) Maternal-fetal transfer of melatonin in pregnant women near term. J Pineal Res 25:129–134
Reiter RJ (1998) Oxidative damage in the central nervous system: protection by melatonin. Prog Neurobiol 56:359–384
Yellon SM, Longo LD (1988) Effect of maternal pinealectomy and reverse photoperiod on the circadian melatonin rhythm in the sheep and fetus during the last trimester of pregnancy. Biol Reprod 39:1093–1099
McMillen IC, Nowak R (1989) Maternal pinealectomy abolishes the diurnal rhythm in plasma melatonin concentrations in the fetal sheep and pregnant ewe during late gestation. J Endocrinol 120:459–464
Torres-Farfan C et al (2004) Maternal melatonin selectively inhibits cortisol production in the primate fetal adrenal gland. J Physiol 554:841–856
Mendez N et al (2012) Timed maternal melatonin treatment reverses circadian disruption of the fetal adrenal clock imposed by exposure to constant light. PLoS One 7:e42713
Torres-Farfan C et al (2008) Evidence of a role for melatonin in fetal sheep physiology: direct actions of melatonin on fetal cerebral artery, brown adipose tissue and adrenal gland. J Physiol 586:4017–4027
Bellavia SL, Carpentieri AR, Vaque AM, Macchione AF, Vermouth NT (2006) Pup circadian rhythm entrainment–effect of maternal ganglionectomy or pinealectomy. Physiol Behav 89:342–349
Seron-Ferre M et al (2013) Impact of chronodisruption during primate pregnancy on the maternal and newborn temperature rhythms. PLoS One 8:e57710
Galdames HA, Torres-Farfan C, Spichiger C, Mendez N, Abarzua-Catalan L, Alonso-Vazquez P, Richter HG (2014) Impact of gestational chronodisruption on fetal cardiac genomics. J Mol Cell Cardiol 66:1–11
Rivkees SA, Mayes L, Jacobs H, Gross I (2004) Rest-activity patterns of premature infants are regulated by cycled lighting. Pediatrics 113: 833–839
Watanabe S, Akiyama S, Hanita T, Li H, Nakagawa M, Kaneshi Y, Ohta H (2013) Designing artificial environments for preterm infants based on circadian studies on pregnant uterus. Front Endocrinol (Lausanne) 4:113
Vasquez-Ruiz S, Maya-Barrios JA, Torres-Narvaez P, Vega-Martinez BR, Rojas-Granados A, Escobar C, Angeles-Castellanos M (2014) A light/dark cycle in the NICU accelerates body weight gain and shortens time to discharge in preterm infants. Early Hum Dev 90:535
Cunningham FG, Leveno K, Bloom S, Hauth J, Rouse D, Spong CY (2009) Maternal and fetal anatomy and physiology. In: Fried A, Davis K (eds) Williams obstetrics. McGraw-Hill Professional Publishing, New York, NY, pp 107–136
Brunton PJ, Russell JA (2008) The expectant brain: adapting for motherhood. Nat Rev Neurosci 9:11–25
Schrader JA, Nunez AA, Smale L (2010) Changes in and dorsal to the rat suprachiasmatic nucleus during early pregnancy. Neuroscience 171:513–523
Schrader JA, Smale L, Nunez AA (2012) Pregnancy affects FOS rhythms in brain regions regulating sleep/wake state and body temperature in rats. Brain Res 1480:53–60
Schrader JA, Nunez AA, Smale L (2011) Site-specific changes in brain extra-SCN oscillators during early pregnancy in the rat. J Biol Rhythms 26:363–367
Varcoe TJ, Boden MJ, Voultsios A, Salkeld MD, Rattanatray L, Kennaway DJ (2013) Characterisation of the maternal response to chronic phase shifts during gestation in the rat: implications for fetal metabolic programming. PLoS One 8:e53800
Wharfe MD, Mark PJ, Waddell BJ (2011) Circadian variation in placental and hepatic clock genes in rat pregnancy. Endocrinology 152:3552–3560
Tamura H, Nakamura Y, Terron MP, Flores LJ, Manchester LC, Tan DX, Sugino N, Reiter RJ (2008) Melatonin and pregnancy in the human. Reprod Toxicol 25:291–303
de Weerth C, Buitelaar JK (2005) Physiological stress reactivity in human pregnancy – a review. Neurosci Biobehav Rev 29:295–312
Brunton PJ, Russell JA (2010) Prenatal social stress in the rat programmes neuroendocrine and behavioural responses to stress in the adult offspring: sex-specific effects. J Neuroendocrinol 22:258–271
Schrader JA, Walaszczyk EJ, Smale L (2009) Changing patterns of daily rhythmicity across reproductive states in diurnal female Nile grass rats (Arvicanthis niloticus). Physiol Behav 98:547–556
Kittrell EM, Satinoff E (1988) Diurnal rhythms of body temperature, drinking and activity over reproductive cycles. Physiol Behav 42:477–484
Ebisawa T (2007) Circadian rhythms in the CNS and peripheral clock disorders: human sleep disorders and clock genes. J Pharmacol Sci 103:150–154
Jilg A, Lesny S, Peruzki N, Schwegler H, Selbach O, Dehghani F, Stehle JH (2010) Temporal dynamics of mouse hippocampal clock gene expression support memory. Hippocampus 20:377–388
Marcheva B, Ramsey KM, Peek CB, Affinati A, Maury E, Bass J (2013) Circadian clocks and metabolism. Handb Exp Pharmacol (217): 127–155
Sadacca LA, Lamia KA, deLemos AS, Blum B, Weitz CJ (2011) An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice. Diabetologia 54:120–124
Matsumoto T, Hess DL, Kaushal KM, Valenzuela GJ, Yellon SM, Ducsay CA (1991) Circadian myometrial and endocrine rhythms in the pregnant rhesus macaque: effects of constant light and timed melatonin infusion. Am J Obstet Gynecol 165:1777–1784
Varcoe TJ, Wight N, Voultsios A, Salkeld MD, Kennaway DJ (2011) Chronic phase shifts of the photoperiod throughout pregnancy programs glucose. PLoS One 6:e18504
Osmond C, Barker DJ (2000) Fetal, infant, and childhood growth are predictors of coronary heart disease, diabetes, and hypertension in adult men and women. Environ Health Perspect 108:545–553
Fowden AL, Giussani DA, Forhead AJ (2006) Intrauterine programming of physiological systems: causes and consequences. Physiology (Bethesda) 21:29–37
Nathanielsz PW (2006) Animal models that elucidate basic principles of the developmental origins of adult diseases. ILAR J 47:73–82
Nuyt AM (2008) Mechanisms underlying developmental programming of elevated blood pressure and vascular dysfunction: evidence from human studies and experimental animal models. Clin Sci (Lond) 114:1–17
Barker DJ (2006) Adult consequences of fetal growth restriction. Clin Obstet Gynecol 49:270–283
Ferreira DS et al (2012) Maternal melatonin programs the daily pattern of energy metabolism in adult offspring. PLoS One 7:e38795
Zhu JL, Hjollund NH, Andersen AM, Olsen J (2004) Shift work, job stress, and late fetal loss: the National Birth Cohort in Denmark. J Occup Environ Med 46:1144–1149
Taylor NF, Martin MC, Nathanielsz PW, Seron-Ferre M (1983) The fetus determines circadian oscillation of myometrial electromyographic activity in the pregnant rhesus monkey. Am J Obstet Gynecol 146:557–567
Figueroa JP, Honnebier MB, Jenkins S, Nathanielsz PW (1990) Alteration of 24-hour rhythms in myometrial activity in the chronically catheterized pregnant rhesus monkey after a 6-hour shift in the light-dark cycle. Am J Obstet Gynecol 163:648–654
Jensen EC, Bennet L, Guild SJ, Booth LC, Stewart J, Gunn AJ (2009) The role of the neural sympathetic and parasympathetic systems in diurnal and sleep state-related cardiovascular rhythms in the late-gestation ovine fetus. Am J Physiol Regul Integr Comp Physiol 297:R998–R1008
Houdek P, Polidarova L, Novakova M, Mateju K, Kubik S, Sumova A (2015) Melatonin administered during the fetal stage affects circadian clock in the suprachiasmatic nucleus but not in the liver. Dev Neurobiol 75:131
Li C, Yu S, Zhong X, Wu J, Li X (2012) Circadian rhythms of fetal liver transcription persist in the absence of canonical circadian clock gene expression rhythms in vivo. PLoS One 7:e30781
Akiyama S et al (2010) The uterus sustains stable biological clock during pregnancy. Tohoku J Exp Med 221:287–298
Ratajczak CK, Herzog ED, Muglia LJ (2010) Clock gene expression in gravid uterus and extra-embryonic tissues during late gestation in the mouse. Reprod Fertil Dev 22:743–750
Ohta H et al (2008) Maternal feeding controls fetal biological clock. PLoS One 3:e2601
Seron-Ferre M, Ducsay CA, Valenzuela GJ (1993) Circadian rhythms during pregnancy. Endocr Rev 14:594–609
Seron-Ferre M, Riffo R, Valenzuela GJ, Germain AM (2001) Twenty-four-hour pattern of cortisol in the human fetus at term. Am J Obstet Gynecol 184:1278–1283
Refinetti R, Lissen GC, Halberg F (2007) Procedures for numerical analysis of circadian rhythms. Biol Rhythm Res 38:275–325
Zar J (1974) Circular distributions. In: McElroy W, Swanson C (eds) Biostatistical analysis. Prentice-Hall, Englewood Cliffs, NJ, pp 310–328
Acknowledgments
ANILLO ACT-1116; FONDECYT 1110220 and 1120938 (Chile).
We thank Monica Prizant for editorial assistance.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Science+Business Media New York
About this protocol
Cite this protocol
Serón-Ferré, M., Richter, H.G., Valenzuela, G.J., Torres-Farfan, C. (2016). Circadian Rhythms in the Fetus and Newborn: Significance of Interactions with Maternal Physiology and the Environment. In: Walker, D. (eds) Prenatal and Postnatal Determinants of Development. Neuromethods, vol 109. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3014-2_7
Download citation
DOI: https://doi.org/10.1007/978-1-4939-3014-2_7
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-3013-5
Online ISBN: 978-1-4939-3014-2
eBook Packages: Springer Protocols