Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Circadian clock genes in reproductive tissues and the developing conceptus

Hamid Dolatshad A C , Fred C. Davis A and Martin H. Johnson B
+ Author Affiliations
- Author Affiliations

A Department of Biology, Northeastern University, Boston, MA 02115, USA.

B Department of Physiology, Development and Neuroscience, The Anatomy School and Centre for Trophoblast Research, Downing Street, Cambridge, CB2 3DY, UK.

C Corresponding author. Email: hd241@cantab.net

Reproduction, Fertility and Development 21(1) 1-9 https://doi.org/10.1071/RD08223
Published: 9 December 2008

Abstract

The circadian (near 24-h) clock is involved in the temporal organisation of physiological and biochemical activities of many organisms, including humans. The clock functions through the rhythmic transcription and translation of several genes, forming an oscillatory feedback loop. Genetic analysis has shown that the circadian clock exists in both a central circadian pacemaker (i.e. the suprachiasmatic nucleus of the hypothalamus), as well as in most peripheral tissues. In particular, the circadian clockwork genes are expressed in all female and male reproductive tissues studied so far, as well as in the conceptus itself. The current data clearly show a robust rhythm in female reproductive tissues, but whether rhythmicity also exists in male reproductive tissues remains uncertain. Although the conceptus also expresses most of the canonical circadian genes, the rhythmicity of their expression is still under investigation. Published data indicate that environmental and genetic manipulations influence reproductive function and fecundity, suggesting an important role for the circadian clock in reproduction, and possibly early development.


Acknowledgements

The authors thank Michael H. Hastings and Elizabeth S. Maywood for Luciferase data collection and helpful comments. H.D. and M.H.J. acknowledge support from the Wellcome Trust (No. 064588/Z/01 to M.H.J. and M.H. Hastings).


References

Akhtar, R. A. , Reddy, A. B. , Maywood, E. S. , Clayton, J. D. , King, V. M. , Smith, A. G. , Gant, T. W. , Hastings, M. H. , and Kyriacou, C. P. (2002). Circadian cycling of the mouse liver transcriptome, as revealed by cDNA microarray, is driven by the suprachiasmatic nucleus. Curr. Biol. 12, 540–550.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS | Dolatshad H. (2006). Expression and role of circadian canonical genes in reproductive tissues. PhD thesis, University of Cambridge.

Dolatshad, H. , Campbell, E. A. , O’Hara, L. , Maywood, E. S. , Hastings, M. H. , and Johnson, M. H. (2006). Developmental and reproductive performance in circadian mutant mice. Hum. Reprod. 21, 68–79.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS | Hastings M. H., Reddy A. B., McMahon D. G., Maywood E. S., and Michael W. Y. (2005). Analysis of circadian mechanisms in the suprachiasmatic nucleus by transgenesis and biolistic transfection. In ‘Methods in Enzymology’. (Ed. M. Young.) pp. 579–592. (Academic Press.)

Hastings, M. , O’Neill, J. S. , and Maywood, E. S. (2007). Circadian clocks: regulators of endocrine and metabolic rhythms. J. Endocrinol. 195, 187–198.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS | Johnson M. H. (2007). ‘Essential Reproduction.’ (Wiley-Blackwell: Oxford.)

Johnson, M. H. , and Day, M. L. (2000). Egg timers: how is developmental time measured in the early vertebrate embryo? Bioessays 22, 57–63.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS | Nakamura T. J., Sellix M. T., Menaker M., and Block G. D. (2008). Estrogen directly modulates circadian rhythms of PER2 expression in the uterus. Am. J. Physiol. Endocrinol. Metab., in press.

Ohta, H. , Xu, S. , Moriya, T. , Iigo, M. , and Watanabe, T. , et al. (2008). Maternal feeding controls fetal biological clock. PLoS One 3, e2601.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Oishi, K. , Sakamoto, K. , Okada, T. , Nagase, T. , and Ishida, N. (1998). Antiphase circadian expression between BMAL1 and period homologue mRNA in the suprachiasmatic nucleus and peripheral tissues of rats. Biochem. Biophys. Res. Commun. 253, 199–203.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Oishi, K. , Fukui, H. , and Ishida, N. (2000). Rhythmic expression of BMAL1 mRNA is altered in Clock mutant mice: differential regulation in the suprachiasmatic nucleus and peripheral tissues. Biochem. Biophys. Res. Commun. 268, 164–171.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Okamura, H. , Yamaguchi, S. , Yagita, K. , King, D. P. , and Takahashi, J. S. (2002). Molecular machinery of the circadian clock in mammals. Cell Tissue Res. 309, 47–56.
Crossref | GoogleScholarGoogle Scholar | CAS | PubMed |

Panda, S. , Antoch, M. P. , Miller, B. H. , Su, A. I. , Schook, A. B. , Straume, M. , Schultz, P. G. , Kay, S. A. , Takahashi, J. S. , and Hogenesch, J. B. (2002). Coordinated transcription of key pathways in the mouse by the circadian clock. Cell 109, 307–320.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Pilorz, V. , and Steinlechner, S. (2008). Low reproductive success in Per1 and Per2 mutant mouse females due to accelerated ageing? Reproduction 135, 559–568.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Reppert, S. M. , and Schwartz, W. J. (1984). The suprachiasmatic nuclei of the fetal rat: characterization of a functional circadian clock using 14C-labeled deoxyglucose. J. Neurosci. 4, 1677–1682.
PubMed |  CAS |

Reppert, S. M. , and Uhl, G. R. (1987). Vasopressin messenger ribonucleic acid in supraoptic and suprachiasmatic nuclei: appearance and circadian regulation during development. Endocrinology 120, 2483–2487.
PubMed |  CAS |

Reppert, S. M. , Henshaw, D. , Schwartz, W. J. , and Weaver, D. R. (1987). The circadian-gated timing of birth in rats: disruption by maternal SCN lesions or by removal of the fetal brain. Brain Res. 403, 398–402.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Rush, B. L. , Murad, A. , Emery, P. , and Giebultowicz, J. M. (2006). Ectopic CRYPTOCHROME renders TIM light sensitive in the Drosophila ovary. J. Biol. Rhythms 21, 272–278.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Saxena, M. T. , Aton, S. J. , Hildebolt, C. , Prior, J. L. , Abraham, U. , Piwnica-Worms, D. , and Herzog, E. D. (2007). Bioluminescence imaging of period1 gene expression in utero. Mol. Imaging 6, 68–72.
PubMed |  CAS |

Seron-Ferre, M. , Valenzuela, G. J. , and Torres-Farfan, C. (2007). Circadian clocks during embryonic and fetal development. Birth Defects Res. C Embryo Today 81, 204–214.
Crossref | GoogleScholarGoogle Scholar | CAS | PubMed |

Shimomura, H. , Moriya, T. , Sudo, M. , Wakamatsu, H. , Akiyama, M. , Miyake, Y. , and Shibata, S. (2001). Differential daily expression of Per1 and Per2 mRNA in the suprachiasmatic nucleus of fetal and early postnatal mice. Eur. J. Neurosci. 13, 687–693.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Sládek, M. , Sumová, A. , Kováciková, Z. , Bendová, Z. , Laurinová, K. , and Illnerová, H. (2004). Insight into molecular core clock mechanism of embryonic and early postnatal rat suprachiasmatic nucleus. Proc. Natl Acad. Sci. USA 101, 6231–6236.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Tei, H. , Okamura, H. , Shigeyoshi, Y. , Fukuhara, C. , Ozawa, R. , Hirose, M. , and Sakaki, Y. (1997). Circadian oscillation of a mammalian homologue of the Drosophila period gene. Nature 389, 512–516.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Tong, Y. , Guo, H. , Brewer, J. M. , Lee, H. , Lehman, M. N. , and Bittman, E. L. (2004). Expression of haPer1 and haBmal1 in Syrian hamsters: heterogeneity of transcripts and oscillations in the periphery. J. Biol. Rhythms 19, 113–125.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Torres-Farfan, C. , Rocco, V. , Monso, C. , Valenzuela, F. J. , Campino, C. , Germain, A. , Torrealba, F. , Valenzuela, G. J. , and Seron-Ferre, M. (2006). Maternal melatonin effects on clock gene expression in a nonhuman primate fetus. Endocrinology 147, 4618–4626.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Turek, F. W. , Swann, J. , and Earnest, D. J. (1984). Role of the circadian system in reproductive phenomena. Recent Prog. Horm. Res. 40, 143–183.
PubMed |  CAS |

Viswanathan, N. , and Davis, F. C. (1997). Single prenatal injections of melatonin or the D1-dopamine receptor agonist SKF 38393 to pregnant hamsters sets the offsprings’ circadian rhythms to phases 180 degrees apart. J. Comp. Physiol. [A] 180, 339–346.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Yamada, K. , Kawata, H. , Mizutani, T. , Arima, T. , and Yazawa, T. , et al. (2004). Gene expression of basic helix-loop-helix transcription factor, SHARP-2, is regulated by gonadotropins in the rat ovary and MA-10 cells. Biol. Reprod. 70, 76–82.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Yamamoto, T. , Nakahata, Y. , Soma, H. , Akashi, M. , Mamine, T. , and Takumi, T. (2004). Transcriptional oscillation of canonical clock genes in mouse peripheral tissues. BMC Mol. Biol. 5, 18.
Crossref | GoogleScholarGoogle Scholar | PubMed |

Yoo, S. H. , Yamazaki, S. , Lowrey, P. L. , Shimomura, K. , and Ko, C. H. , et al. (2004). PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues. Proc. Natl Acad. Sci. USA 101, 5339–5346.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Ziv, L. , and Gothilf, Y. (2006). Circadian time-keeping during early stages of development. Proc. Natl Acad. Sci. USA 103, 4146–4151.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |

Zylka, M. J. , Shearman, L. P. , Weaver, D. R. , and Reppert, S. M. (1998). Three period homologs in mammals: differential light responses in the suprachiasmatic circadian clock and oscillating transcripts outside of brain. Neuron 20, 1103–1110.
Crossref | GoogleScholarGoogle Scholar | PubMed | CAS |