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Review

The Circadian Clock, Nutritional Signals and Reproduction: A Close Relationship

by
Masanori Ono
1,2,*,
Hitoshi Ando
3,
Takiko Daikoku
4,
Tomoko Fujiwara
5,
Michihiro Mieda
6,
Yasunari Mizumoto
2,
Takashi Iizuka
2,
Kyosuke Kagami
2,
Takashi Hosono
2,
Satoshi Nomura
2,
Natsumi Toyoda
2,4,
Naomi Sekizuka-Kagami
7,
Yoshiko Maida
7,
Naoaki Kuji
1,
Hirotaka Nishi
1 and
Hiroshi Fujiwara
2
1
Department of Obstetrics and Gynecology, Tokyo Medical University, Tokyo 160-0023, Japan
2
Department of Obstetrics and Gynecology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8641, Japan
3
Department of Cellular and Molecular Function Analysis, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8641, Japan
4
Institute for Experimental Animals, Advanced Science Research Center, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8641, Japan
5
Department of Social Work and Life Design, Kyoto Notre Dame University, Kyoto 606-0848, Japan
6
Department of Integrative Neurophysiology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8641, Japan
7
Department of Nursing, College of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa 920-8641, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(2), 1545; https://doi.org/10.3390/ijms24021545
Submission received: 14 December 2022 / Revised: 8 January 2023 / Accepted: 9 January 2023 / Published: 12 January 2023
(This article belongs to the Special Issue Circadian Clock and Reproduction)
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Abstract

The circadian rhythm, which is necessary for reproduction, is controlled by clock genes. In the mouse uterus, the oscillation of the circadian clock gene has been observed. The transcription of the core clock gene period (Per) and cryptochrome (Cry) is activated by the heterodimer of the transcription factor circadian locomotor output cycles kaput (Clock) and brain and muscle Arnt-like protein-1 (Bmal1). By binding to E-box sequences in the promoters of Per1/2 and Cry1/2 genes, the CLOCK-BMAL1 heterodimer promotes the transcription of these genes. Per1/2 and Cry1/2 form a complex with the Clock/Bmal1 heterodimer and inactivate its transcriptional activities. Endometrial BMAL1 expression levels are lower in human recurrent-miscarriage sufferers. Additionally, it was shown that the presence of BMAL1-depleted decidual cells prevents trophoblast invasion, highlighting the importance of the endometrial clock throughout pregnancy. It is widely known that hormone synthesis is disturbed and sterility develops in Bmal1-deficient mice. Recently, we discovered that animals with uterus-specific Bmal1 loss also had poor placental development, and these mice also had intrauterine fetal death. Furthermore, it was shown that time-restricted feeding controlled the uterine clock’s circadian rhythm. The uterine clock system may be a possibility for pregnancy complications, according to these results. We summarize the most recent research on the close connection between the circadian clock and reproduction in this review.
Keywords: BMAL1; circadian rhythm; clock gene; miscarriage; pregnancy; reproduction BMAL1; circadian rhythm; clock gene; miscarriage; pregnancy; reproduction

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MDPI and ACS Style

Ono, M.; Ando, H.; Daikoku, T.; Fujiwara, T.; Mieda, M.; Mizumoto, Y.; Iizuka, T.; Kagami, K.; Hosono, T.; Nomura, S.; et al. The Circadian Clock, Nutritional Signals and Reproduction: A Close Relationship. Int. J. Mol. Sci. 2023, 24, 1545. https://doi.org/10.3390/ijms24021545

AMA Style

Ono M, Ando H, Daikoku T, Fujiwara T, Mieda M, Mizumoto Y, Iizuka T, Kagami K, Hosono T, Nomura S, et al. The Circadian Clock, Nutritional Signals and Reproduction: A Close Relationship. International Journal of Molecular Sciences. 2023; 24(2):1545. https://doi.org/10.3390/ijms24021545

Chicago/Turabian Style

Ono, Masanori, Hitoshi Ando, Takiko Daikoku, Tomoko Fujiwara, Michihiro Mieda, Yasunari Mizumoto, Takashi Iizuka, Kyosuke Kagami, Takashi Hosono, Satoshi Nomura, and et al. 2023. "The Circadian Clock, Nutritional Signals and Reproduction: A Close Relationship" International Journal of Molecular Sciences 24, no. 2: 1545. https://doi.org/10.3390/ijms24021545

APA Style

Ono, M., Ando, H., Daikoku, T., Fujiwara, T., Mieda, M., Mizumoto, Y., Iizuka, T., Kagami, K., Hosono, T., Nomura, S., Toyoda, N., Sekizuka-Kagami, N., Maida, Y., Kuji, N., Nishi, H., & Fujiwara, H. (2023). The Circadian Clock, Nutritional Signals and Reproduction: A Close Relationship. International Journal of Molecular Sciences, 24(2), 1545. https://doi.org/10.3390/ijms24021545

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