Hostname: page-component-54dcc4c588-tfzs5 Total loading time: 0 Render date: 2025-09-16T00:48:12.966Z Has data issue: false hasContentIssue false
  • English
  • Français

The effects of circadian rhythm on reproductive functions

Published online by Cambridge University Press:  10 September 2025

Seda Karabulut Open the ORCID record for Seda Karabulut [Opens in a new window]  and
Lima Oria Open the ORCID record for Lima Oria [Opens in a new window]
Seda Karabulut*
Affiliation:
Department of Histology and Embryology, International School of Medicine, Istanbul Medipol University, Istanbul, Turkey
Lima Oria
Affiliation:
International School of Medicine, Istanbul Medipol University, Istanbul, Turkey
*
Corresponding author: Seda Karabulut; Email: Seda.karabulut@medipol.edu.tr
Get access Rights & Permissions [Opens in a new window]

Abstract

Circadian rhythms are intrinsic, endogenously generated cycles that regulate various physiological processes, including reproductive functions. These rhythms are orchestrated by a network of core clock genes and are influenced by external environmental cues, primarily the light–dark cycle. Disruptions in circadian rhythms can have profound effects on fertility in both males and females, impacting processes such as the estrous cycle, ovulation, sperm production, implantation and pregnancy maintenance. This review comprehensively explores the molecular mechanisms underlying circadian rhythms and their influence on reproductive health, integrating evidence from both animal models and human studies. We delve into the intricate interplay between circadian genes, hormonal regulation and environmental factors, underscoring the critical importance of circadian integrity for optimal reproductive outcomes. The potential therapeutic implications of maintaining circadian rhythms are also discussed, highlighting novel avenues for enhancing reproductive health.

Keywords

Circadian rhythmReproductionFertilityClock genesHormonal regulation

Information

Type
Review Article
Information
Zygote , First View , pp. 1 - 7
Check for updates
Copyright
© The Author(s), 2025. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Alvarez, J.D., Hansen, A., Ord, T., Bebas, P., Chappell, P.E., Giebultowicz, J.M., et al. (2008) The circadian clock protein Bmal1 is necessary for fertility and proper testosterone production in mice. Journal of Biological Rhythms 23(1), 26–36.10.1177/0748730407311254CrossRefGoogle ScholarPubMed
Anderson, S.T., Morgan, M.A. and Brown, A. (2023) Circadian rhythm disruption and fertility: clinical implications and mechanistic links. Reproductive Biology and Endocrinology 21(1), 15. https://doi.org/10.1186/s12958-023-00994-y Google Scholar
Boden, M.J. and Kennaway, D.J. (2006) Circadian rhythms and reproduction. Reproduction 132(3), 379–392.10.1530/rep.1.00614CrossRefGoogle ScholarPubMed
Boden, M.J., Varcoe, T.J., Voultsios, A. and Kennaway, D.J. (2010) Reproductive biology of female Bmal1 null mice. Reproduction 139(6), 1077–1090.10.1530/REP-09-0523CrossRefGoogle ScholarPubMed
Brito, K.M., Tello, J., Wang, X., et al. (2023) Epigenetic consequences of circadian disruption in germline and embryo development. Nature Reviews Molecular Cell Biology 24(2), 89–101. https://doi.org/10.1038/s41580-022-00535-2 Google Scholar
Challet, E., van der Spek, R. and Garaulet, M. (2022) Chrononutrition and fertility: synchronizing food intake and the circadian clock to optimize reproductive health. Nutrients 14(19), 3998. https://doi.org/10.3390/nu14193998 Google Scholar
Chappell, P.E., White, R.S., Mellon, P.L. (2003) Circadian gene expression regulates pulsatile GnRH secretion in reproductive neuroendocrine cells. Endocrinology 144(10), 4544–4550. https://doi.org/10.1210/en.2003-0552 Google Scholar
De Mairan, J.J. (1729) Observation botanique. Histoire de l’Académie Royale des Sciences 35, 265–270.Google Scholar
Doudna, J.A. and Charpentier, E. (2014) The new frontier of genome engineering with CRISPR–Cas9. Science 346(6213), 1258096. https://doi.org/10.1126/science.1258096 CrossRefGoogle ScholarPubMed
Fahrenkrug, J., Georg, B., Hannibal, J., Hindersson, P. and Gras, S. (2006) Diurnal rhythmicity of the clock genes Per1 and Per2 in the rat ovary. Endocrinology 147(8), 3769–3776.10.1210/en.2006-0305CrossRefGoogle ScholarPubMed
Foster, R.G. and Kreitzman, L. (2014) The rhythms of life: what your body clock means to you. Experimental Physiology 99(4), 599–606. https://doi.org/10.1113/expphysiol.2012.071118 CrossRefGoogle ScholarPubMed
Guo, J., Li, S., Zhang, T., et al. (2023) The timing of physical activity influences reproductive hormone profiles in women with disrupted circadian rhythms. Frontiers in Endocrinology 14, 1172047. https://doi.org/10.3389/fendo.2023.1172047 Google Scholar
Halberg, F. (1960) Physiologic 24-hour periodicity; general and procedural considerations with reference to the adrenal cycle. Z Vitam Horm Fermentforsch 10, 225–246.Google Scholar
Hastings, M.H., Reddy, A.B. and Maywood, E.S. (2003) A clockwork web: circadian timing in brain and periphery, in health and disease. Nature Reviews Neuroscience 4(8), 649–661.10.1038/nrn1177CrossRefGoogle ScholarPubMed
Hirota, T., Lee, J.W., St John, P.C., Sawa, M., Iwaisako, K., Noguchi, T., Pongsawakul, P.Y., Sonntag, T., Welsh, D.K., Brenner, D.A., Doyle, F.J. and Kay, S.A. (2012) Identification of small molecule activators of cryptochrome. Science 337(6098), 1094–1097. https://doi.org/10.1126/science.1223710 CrossRefGoogle ScholarPubMed
Kovanen, L., Saarikoski, S.T., Aromaa, A., Lönnqvist, J. and Partonen, T. (2010) ARNTL (Bmal1) and NPAS2 gene variants contribute to fertility and seasonality. PLoS ONE 5(4), e10007.10.1371/journal.pone.0010007CrossRefGoogle ScholarPubMed
Kennaway, D.J. (2005) The role of circadian rhythmicity in reproduction. Human Reproduction Update 11(1), 91–101.10.1093/humupd/dmh054CrossRefGoogle ScholarPubMed
Kennaway, D.J., Boden, M.J. and Voultsios, A. (2004) Reproductive performance in female Clock mutant mice. Reproduction, Fertility and Development 16(7), 801–810.10.1071/RD04023CrossRefGoogle Scholar
Labyak, S., Lava, S., Turek, F. and Zee, P. (2002) Effects of shiftwork on sleep and menstrual function in nurses. Health Care for Women International 23(6–7), 703–714.10.1080/07399330290107449CrossRefGoogle ScholarPubMed
Liu, Z., Li, X.M., Liu, Y., Xie, J., Wu, J. and Zhou, S. (2017) Essential roles of BMAL1 in reproductive physiology and fertility. Reproduction 154(5), 321–331. https://doi.org/10.1530/REP-17-0102 Google Scholar
Mahoney, M.M. (2010) Shift work, jet lag, and female reproduction. International Journal of Endocrinology 2010, 813764. https://doi.org/10.1155/2010/813764 CrossRefGoogle ScholarPubMed
Moore, R.Y. and Eichler, V.B. (1972) Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat. Brain Research 42(1), 201–206.10.1016/0006-8993(72)90054-6CrossRefGoogle ScholarPubMed
Mukherjee, S., Patel, R. and Jain, R. (2022) Melatonin suppression and reproductive dysfunction following environmental exposure to endocrine disruptors: a mechanistic overview. Journal of Pineal Research 73(2), e12856. https://doi.org/10.1111/jpi.12856 Google Scholar
Nakamura, T.J., Sellix, M.T. and Menaker, M. (2022) The circadian system and fertility: a clinical update on chronotherapy. Fertility and Sterility 118(5), 803–811. https://doi.org/10.1016/j.fertnstert.2022.07.003 Google Scholar
Panda, S., Hogenesch, J.B. and Kay, S.A. (2002) Circadian rhythms from flies to human. Nature 417(6886), 329–335. https://doi.org/10.1038/417329a CrossRefGoogle ScholarPubMed
Pittendrigh, C.S. (1960) Circadian rhythms and the circadian organization of living systems. Cold Spring Harbor Symposia on Quantitative Biology 25, 159–184.10.1101/SQB.1960.025.01.015CrossRefGoogle ScholarPubMed
Reiter, R.J., Tan, D.X., Korkmaz, A., Rosales-Corral, S.A. and Manchester, L.C. (2014) The circadian melatonin rhythm and its modulation: possible impact on human reproduction. Fertility and Sterility 102(2), 321–328.10.1016/j.fertnstert.2014.06.014CrossRefGoogle Scholar
Reppert, S.M. and Weaver, D.R. (2002) Coordination of circadian timing in mammals. Nature 418(6901), 935–941.10.1038/nature00965CrossRefGoogle ScholarPubMed
Roenneberg, T. and Merrow, M. (2016) The circadian clock and human health. Current Biology 26(10), R432–R443. https://doi.org/10.1016/j.cub.2016.04.011 CrossRefGoogle ScholarPubMed
Schiavi, M.C., Faiano, P., D’Oria, O., et al. (2022) Circadian rhythm and female genital tract: interactions with microbiota and implications for fertility. Reproductive Sciences 29(4), 1102–1111. https://doi.org/10.1007/s43032-021-00638-0 Google Scholar
Silver, R., LeSauter, J., Tresco, P.A. and Lehman, M.N. (1996) A diffusible coupling signal from the transplanted suprachiasmatic nucleus controlling circadian locomotor rhythms. Nature 382(6594), 810–813.10.1038/382810a0CrossRefGoogle ScholarPubMed
Stanton, M.E., Chang, L., Barakat, R., et al. (2023) Circadian gene expression regulates preimplantation development and blastocyst quality. Reproduction 165(2), R101–R113. https://doi.org/10.1530/REP-23-0104 Google Scholar
Vetter, C., Devore, E.E., Wegrzyn, L.R., Massa, J., Speizer, F.E., Kawachi, I. and Schernhammer, E.S. (2018) Association between rotating night shift work and risk of coronary heart disease among women. JAMA 320(23), 2448–2458. https://doi.org/10.1001/jama.2018.14276 Google Scholar
Vollmers, C., Gill, S., DiTacchio, L., et al. (2022) Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression. Nature 603(7902), 611–617. https://doi.org/10.1038/s41586-022-04566-6 Google Scholar
Waters, A. and Devaney, T. (2013) The role of exercise in maintaining health and preventing disease: an analysis of circadian rhythms and hormonal balance. Journal of Endocrinology 219(1), R25–R36.Google Scholar
Wright, K.P. Jr, McHill, A.W., Birks, B.R., Griffin, B.R., Rusterholz, T. and Chinoy, E.D. (2013) Entrainment of the human circadian clock to the natural light–dark cycle. Current Biology 23(16), 1554–1558. https://doi.org/10.1016/j.cub.2013.06.039 CrossRefGoogle Scholar
Xie, Y., Ma, C., Zhou, J., et al. (2022) Clock gene expression and oocyte quality: circadian control of zygote competence. Cell and Tissue Research 388(3), 491–502. https://doi.org/10.1007/s00441-021-03568-z Google Scholar
Xu, C., Hu, Y., Liu, Y., Chen, Q. and Sun, H. (2023) Disruption of circadian gene expression by endocrine-disrupting chemicals in ovarian and testicular cells. Frontiers in Endocrinology 14, 1182435. https://doi.org/10.3389/fendo.2023.1182435 Google Scholar
Yang, H., Lee, K., Jeong, J.Y., et al. (2021) Disruption of CLOCK- Bmal1 impairs spermiogenesis and sperm DNA integrity in mice. Biology of Reproduction 105(2), 458–468. https://doi.org/10.1093/biolre/ioaa212 Google Scholar