scholarly journals Pregnancy-induced changes in the circadian expression of hepatic clock genes: implications for maternal glucose homeostasis

2016 ◽  
Vol 311 (3) ◽  
pp. E575-E586 ◽  
Author(s):  
Michaela D. Wharfe ◽  
Caitlin S. Wyrwoll ◽  
Brendan J. Waddell ◽  
Peter J. Mark
Keyword(s):  
Clock Genes ◽  
Circadian Variation ◽  
Late Gestation ◽  
Hepatic Expression ◽  
Rhythmic Expression ◽  
Circadian Expression ◽  
Clock Gene Expression ◽  
Maternal Adaptation ◽  
Near Term ◽  
In Pregnancy

Adaptations in maternal carbohydrate metabolism are particularly important in pregnancy because glucose is the principal energy substrate used by the fetus. As metabolic homeostasis is intricately linked to the circadian system via the rhythmic expression of clock genes, it is likely that metabolic adaptations during pregnancy also involve shifts in maternal circadian function. We hypothesized that maternal adaptation in pregnancy involves changes in the hepatic expression of clock genes, which drive downstream shifts in circadian expression of glucoregulatory genes. Maternal liver and plasma ( n = 6–8/group) were collected across 24-h periods (0800, 1200, 1600, 2000, 0000, 0400) from C57Bl/6J mice under isoflurane-nitrous oxide anesthesia prior to and on days 6, 10, 14 and 18 of pregnancy (term = day 19). Hepatic expression of clock genes and glucoregulatory genes was determined by RT-qPCR. Hepatic clock gene expression was substantially altered across pregnancy, most notably in late gestation when the circadian rhythmicity of several clock genes was attenuated (≤64% reduced amplitude on day 18). These changes were associated with a similar decline in rhythmicity of the key glucoregulatory genes Pck1, G6Pase, and Gk, and by day 18, Pck1 was no longer rhythmic. Overall, our data show marked adaptations in the liver clock during mouse pregnancy, changes that may contribute to the altered circadian variation in glucoregulatory genes near term. We propose that the observed reduction of daily oscillations in glucose metabolism ensure a sustained supply of glucose to meet the high demands of fetal growth.

scholarly journals Clock gene expression in gravid uterus and extra-embryonic tissues during late gestation in the mouse

2010 ◽  
Vol 22 (5) ◽  
pp. 743 ◽  
Author(s):  
Christine K. Ratajczak ◽  
Erik D. Herzog ◽  
Louis J. Muglia
Keyword(s):  
Molecular Clock ◽  
Clock Genes ◽  
Circadian Rhythmicity ◽  
Late Gestation ◽  
Gravid Uterus ◽  
Fetal Membranes ◽  
Molecular Clocks ◽  
Potential Contribution ◽  
Rhythmic Expression ◽  
Clock Gene Expression

Evidence in humans and rodents suggests the importance of circadian rhythmicity in parturition. A molecular clock underlies the generation of circadian rhythmicity. While this molecular clock has been identified in numerous tissues, the expression and regulation of clock genes in tissues relevant to parturition is largely undefined. Here, the expression and regulation of the clock genes Bmal1, Clock, cryptochrome (Cry1/2) and period (Per1/2) was examined in the murine gravid uterus, placenta and fetal membranes during late gestation. All clock genes examined were expressed in the tissues of interest throughout the last third of gestation. Upregulation of a subset of these clock genes was observed in each of these tissues in the final two days of gestation. Oscillating expression of mRNA for a subset of the examined clock genes was detected in the gravid uterus, placenta and fetal membranes. Furthermore, bioluminescence recording on explants from gravid Per2::luciferase mice indicated rhythmic expression of PER2 protein in these tissues. These data demonstrate expression and rhythmicity of clock genes in tissues relevant to parturition indicating a potential contribution of peripheral molecular clocks to this process.

scholarly journals Rhythmic Clock Gene Expression in Atlantic Salmon Parr Brain

2021 ◽  
Vol 12 ◽  
Author(s):  
Charlotte M. Bolton ◽  
Michaël Bekaert ◽  
Mariann Eilertsen ◽  
Jon Vidar Helvik ◽  
Herve Migaud
Keyword(s):  
Atlantic Salmon ◽  
Clock Genes ◽  
Expression Patterns ◽  
Circadian Expression ◽  
Clock Gene Expression ◽  
Sister Clade ◽  
Before And After ◽  
Salmon Parr ◽  
Species Specific ◽  
Atlantic Salmon Parr

To better understand the complexity of clock genes in salmonids, a taxon with an additional whole genome duplication, an analysis was performed to identify and classify gene family members (clock, arntl, period, cryptochrome, nr1d, ror, and csnk1). The majority of clock genes, in zebrafish and Northern pike, appeared to be duplicated. In comparison to the 29 clock genes described in zebrafish, 48 clock genes were discovered in salmonid species. There was also evidence of species-specific reciprocal gene losses conserved to the Oncorhynchus sister clade. From the six period genes identified three were highly significantly rhythmic, and circadian in their expression patterns (per1a.1, per1a.2, per1b) and two was significantly rhythmically expressed (per2a, per2b). The transcriptomic study of juvenile Atlantic salmon (parr) brain tissues confirmed gene identification and revealed that there were 2,864 rhythmically expressed genes (p < 0.001), including 1,215 genes with a circadian expression pattern, of which 11 were clock genes. The majority of circadian expressed genes peaked 2 h before and after daylight. These findings provide a foundation for further research into the function of clock genes circadian rhythmicity and the role of an enriched number of clock genes relating to seasonal driven life history in salmonids.

Clock Gene Expression in Pregnancy-Related Tissues During Late Gestation in the Mouse.

2009 ◽  
Vol 81 (Suppl_1) ◽  
pp. 291-291
Author(s):  
Christine K. Ratajczak ◽  
Erik D. Herzog ◽  
Louis J. Muglia
Keyword(s):  
Gene Expression ◽  
Clock Gene ◽  
Late Gestation ◽  
Clock Gene Expression ◽  
In Pregnancy

Clock Gene Expression in the Submandibular Glands

2005 ◽  
Vol 84 (12) ◽  
pp. 1193-1197 ◽  
Author(s):  
M. Furukawa ◽  
T. Kawamoto ◽  
M. Noshiro ◽  
K.K. Honda ◽  
M. Sakai ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Clock Gene ◽  
Clock Genes ◽  
Expression Profiles ◽  
Mrna Levels ◽  
Peripheral Tissues ◽  
Submandibular Glands ◽  
Circadian Expression ◽  
Clock Gene Expression

Clock genes, which mediate molecular circadian rhythms, are expressed in a circadian fashion in the suprachiasmatic nucleus and in various peripheral tissues. To establish a molecular basis for circadian regulation in the salivary glands, we examined expression profiles of clock-related genes and salivary gland-characteristic genes. Clock-related genes—including Per1, Per2, Cry1, Bmal1, Dec1, Dec2, Dbp, and Reverbα—showed robust circadian expression rhythms in the submandibular glands in 12:12-hour light-dark conditions. In addition, a robust circadian rhythm was observed in amylase 1 mRNA levels, whereas the expression of other salivary-gland-characteristic genes examined was not rhythmic. The Clock mutation resulted in increased or decreased mRNA levels of Per2, Bmal1, Dec1, Dec2, and Dbp, and in Cry1− /− background, Cry2 disruption also increased or decreased mRNA levels of these clock-related genes and the amylase 1 gene. These findings indicate that the Clock- and Cry-dependent molecular clock system is active in the salivary glands.

scholarly journals Clock Gene Expression in Adult Primate Suprachiasmatic Nuclei and Adrenal: Is the Adrenal a Peripheral Clock Responsive to Melatonin?

Endocrinology ◽  
2008 ◽  
Vol 149 (4) ◽  
pp. 1454-1461 ◽  
Author(s):  
F. J. Valenzuela ◽  
C. Torres-Farfan ◽  
H. G. Richter ◽  
N. Mendez ◽  
C. Campino ◽  
...  
Keyword(s):  
Adrenal Gland ◽  
Clock Gene ◽  
Clock Genes ◽  
Phase Relationship ◽  
Suprachiasmatic Nuclei ◽  
Rhythmic Expression ◽  
Peripheral Oscillators ◽  
Clock Gene Expression ◽  
Timing System ◽  
Circadian Timing System

The circadian production of glucocorticoids involves the concerted action of several factors that eventually allow an adequate adaptation to the environment. Circadian rhythms are controlled by the circadian timing system that comprises peripheral oscillators and a central rhythm generator located in the suprachiasmatic nucleus (SCN) of the hypothalamus, driven by the self-regulatory interaction of a set of proteins encoded by genes named clock genes. Here we describe the phase relationship between the SCN and adrenal gland for the expression of selected core clock transcripts (Per-2, Bmal-1) in the adult capuchin monkey, a New World, diurnal nonhuman primate. In the SCN we found a higher expression of Bmal-1 during the h of darkness (2000–0200 h) and Per-2 during daytime h (1400 h). The adrenal gland expressed clock genes in oscillatory fashion, with higher values for Bmal-1 during the day (1400–2000 h), whereas Per-2 was higher at nighttime (about 0200 h), resulting in a 9- to 12-h antiphase pattern. In the adrenal gland, the oscillation of clock genes was accompanied by rhythmic expression of a functional output, the steroidogenic enzyme 3β-hydroxysteroid dehydrogenase. Furthermore, we show that adrenal explants maintained oscillatory expression of Per-2 and Bmal-1 for at least 36 h in culture. The acrophase of both transcripts, but not its overall expression along the incubation, was blunted by 100 nm melatonin. Altogether, these results demonstrate oscillation of clock genes in the SCN and adrenal gland of a diurnal primate and support an oscillation of clock genes in the adrenal gland that may be modulated by the neurohormone melatonin.

Body temperature regulation in rats near term of pregnancy

1995 ◽  
Vol 73 (3) ◽  
pp. 364-368 ◽  
Author(s):  
James E. Fewell
Keyword(s):  
Body Temperature ◽  
Temperature Regulation ◽  
Dark Period ◽  
Circadian Variation ◽  
Light Period ◽  
Late Gestation ◽  
Body Temperature Regulation ◽  
Near Term

Experiments were carried out to define the effects of pregnancy on body tempreature (Tb) regulation in rats. Tb was measured by biotelemetry in six animals from day 10 of pregnancy (term day 21) to postpartum day 10. Average 24-h Tb decreased from day 15 of gestation to the time of parturition. Furthermore, there was a loss of the normal circadian variation of Tb late in gestation, which was again present by postpartum day 2. The decrease in 24-h Tb on day 15 of gestation resulted from this loss of circadian variation, as Tb did not increase during the dark period. The further decrease in Tb on day 20 of gestation resulted from an overall decrease in Tb during the light and dark periods as well as from a loss of the circadian variation in Tb. Tb increased dramatically within 4 h of birth of the first pup, which always occurred on day 21 during the light period. The mechanisms responsible for these dramatic changes in thermoregulation during late gestation and around the time of parturition are presently unknown.Key words: body temperature, circadian, parturition, pregnancy, rat, thermoregulation.

scholarly journals Circadian Variation in Placental and Hepatic Clock Genes in Rat Pregnancy

Endocrinology ◽  
2011 ◽  
Vol 152 (9) ◽  
pp. 3552-3560 ◽  
Author(s):  
Michaela D. Wharfe ◽  
Peter J. Mark ◽  
Brendan J. Waddell
Keyword(s):  
Clock Genes ◽  
Fetal Liver ◽  
Circadian Variation ◽  
Time Of Day ◽  
Peripheral Tissues ◽  
Clock Gene Expression ◽  
Physiological Processes ◽  
Maternal Liver ◽  
Physiological Adaptations ◽  
Circadian Patterns

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.

scholarly journals The trophoblast clock controls transport across placenta in mice

Development ◽  
2021 ◽  
Vol 148 (8) ◽  
Author(s):  
Cécile Demarez ◽  
Leonardo Vinicius Monteiro De Assis ◽  
Markus Krohn ◽  
Nahuel Ramella ◽  
Markus Schwaninger ◽  
...  
Keyword(s):  
Clock Gene ◽  
Clock Genes ◽  
Treatment Time ◽  
Efflux Pump ◽  
Late Gestation ◽  
Maternal Circulation ◽  
Clock Gene Expression ◽  
Mature Mouse ◽  
Exogenous Compounds ◽  
And Behavior

ABSTRACT In mammals, 24-h rhythms of physiology and behavior are organized by a body-wide network of clock genes and proteins. Despite the well-known function of the adult circadian system, the roles of maternal, fetal and placental clocks during pregnancy are poorly defined. In the mature mouse placenta, the labyrinth zone (LZ) is of fetal origin and key for selective nutrient and waste exchange. Recently, clock gene expression has been detected in LZ and other fetal tissues; however, there is no evidence of a placental function controlled by the LZ clock. Here, we demonstrate that specifically the trophoblast layer of the LZ harbors an already functional clock by late gestation, able to regulate in a circadian manner the expression and activity of the xenobiotic efflux pump, ATP-binding cassette sub-family B member 1 (ABCB1), likely gating the fetal exposure to drugs from the maternal circulation to certain times of the day. As more than 300 endogenous and exogenous compounds are substrates of ABCB1, our results might have implications in choosing the maternal treatment time when aiming either maximal/minimal drug availability to the fetus/mother.

scholarly journals Evidence for Circadian Regulation of Activating Transcription Factor 5 But Not Tyrosine Hydroxylase by the Chromaffin Cell Clock

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5811-5821 ◽  
Author(s):  
Dario R. Lemos ◽  
Leela Goodspeed ◽  
Luciana Tonelli ◽  
Marina P. Antoch ◽  
Sergio R. Ojeda ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Differentiation ◽  
Chromaffin Cells ◽  
Chromaffin Cell ◽  
Clock Genes ◽  
Cell Physiology ◽  
Rhythmic Pattern ◽  
Rhythmic Expression ◽  
Circadian Expression ◽  
Activating Transcription Factor

In mammals, adrenal medulla chromaffin cells constitute a fundamental component of the sympathetic nervous system outflow, producing most of the circulating adrenaline. We recently found that the rhesus monkey adrenal gland expresses several genes in a 24-h rhythmic pattern, including TH (the rate-limiting enzyme in catecholamine synthesis) and Atf5 (a transcription factor involved in apoptosis and neural cell differentiation) together with the core-clock genes. To examine whether these core-clock genes play a role in adrenal circadian function, we exposed rat pheochromocytoma PC12 cells to a serum shock and found that it triggered rhythmic oscillation of the clock genes rBmal1, rPer1, rRev-erbα, and rCry1 and induced the circadian expression of Atf5 but not TH. Furthermore, we found that the CLOCK/brain and muscle Arnt-like protein-1 (BMAL1) heterodimer could regulate Atf5 expression by binding to an E-box motif and repressing activity of its promoter. The physiological relevance of this interaction was evident in Bmal1 −/− mice, in which blunted circadian rhythm of Atf5 mRNA was observed in the liver, together with significantly higher expression levels in both liver and adrenal glands. Although we found no compelling evidence for rhythmic expression of TH in chromaffin cells being regulated by an intrinsic molecular clock mechanism, the Atf5 results raise the possibility that other aspects of chromaffin cell physiology, such as cell survival and cell differentiation, may well be intrinsically regulated.

scholarly journals Pregnancy Suppresses the Daily Rhythmicity of Core Body Temperature and Adipose Metabolic Gene Expression in the Mouse

Endocrinology ◽  
2016 ◽  
Vol 157 (9) ◽  
pp. 3320-3331 ◽  
Author(s):  
Michaela D. Wharfe ◽  
Caitlin S. Wyrwoll ◽  
Brendan J. Waddell ◽  
Peter J. Mark
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Clock Gene ◽  
Clock Genes ◽  
Core Body Temperature ◽  
Rhythmic Expression ◽  
Clock Gene Expression ◽  
Metabolic Genes ◽  
Core Body

Maternal adaptations in lipid metabolism are crucial for pregnancy success due to the role of white adipose tissue as an energy store and the dynamic nature of energy needs across gestation. Because lipid metabolism is regulated by the rhythmic expression of clock genes, it was hypothesized that maternal metabolic adaptations involve changes in both adipose clock gene expression and the rhythmic expression of downstream metabolic genes. Maternal core body temperature (Tc) was investigated as a possible mechanism driving pregnancy-induced changes in clock gene expression. Gonadal adipose tissue and plasma were collected from C57BL/6J mice before and on days 6, 10, 14, and 18 of pregnancy (term 19 d) at 4-hour intervals across a 24-hour period. Adipose expression of clock genes and downstream metabolic genes were determined by quantitative RT-PCR, and Tc was measured by intraperitoneal temperature loggers. Adipose clock gene expression showed robust rhythmicity throughout pregnancy, but absolute levels varied substantially across gestation. Rhythmic expression of the metabolic genes Lipe, Pnpla2, and Lpl was clearly evident before pregnancy; however, this rhythmicity was lost with the onset of pregnancy. Tc rhythm was significantly altered by pregnancy, with a 65% decrease in amplitude by term and a 0.61°C decrease in mesor between days 6 and 18. These changes in Tc, however, did not appear to be linked to adipose clock gene expression across pregnancy. Overall, our data show marked adaptations in the adipose clock in pregnancy, with an apparent decoupling of adipose clock and lipolytic/lipogenic gene rhythms from early in gestation.

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