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Cited by 371Circadian rhythm and melatoninPregnancy and preeclampsia studiesBirth, Development, and Health

Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology

Reiter, Russel J., Tan, Dun Xian, Korkmaz, Ahmet, Rosales-Corral, Sergio A.·2014·Human Reproduction Update
DOI 10.1093/humupd/dmt054
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Abstract

BACKGROUND: Research within the last decade has shown melatonin to have previously-unsuspected beneficial actions on the peripheral reproductive organs. Likewise, numerous investigations have documented that stable circadian rhythms are also helpful in maintaining reproductive health. The relationship of melatonin and circadian rhythmicity to maternal and fetal health is summarized in this review. METHODS: Databases were searched for the related published English literature up to 15 May 2013. The search terms used in various combinations included melatonin, circadian rhythms, biological clock, suprachiasmatic nucleus, ovary, pregnancy, uterus, placenta, fetus, pre-eclampsia, intrauterine growth restriction, ischemia-reperfusion, chronodisruption, antioxidants, oxidative stress and free radicals. The results of the studies uncovered are summarized herein. RESULTS: Both melatonin and circadian rhythms impact reproduction, especially during pregnancy. Melatonin is a multifaceted molecule with direct free radical scavenging and indirect antioxidant activities. Melatonin is produced in both the ovary and in the placenta where it protects against molecular mutilation and cellular dysfunction arising from oxidative/nitrosative stress. The placenta, in particular, is often a site of excessive free radical generation due to less than optimal adhesion to the uterine wall, which leads to either persistent hypoxia or intermittent hypoxia and reoxygenation, processes that cause massive free radical generation and organ dysfunction. This may contribute to pre-eclampsia and other disorders which often complicate pregnancy. Melatonin has ameliorated free radical damage to the placenta and to the fetus in experiments using non-human mammals. Likewise, the maintenance of a regular maternal light/dark and sleep/wake cycle is important to stabilize circadian rhythms generated by the maternal central circadian pacemaker, the suprachiasmatic nuclei. Optimal circadian rhythmicity in the mother is important since her circadian clock, either directly or indirectly via the melatonin rhythm, programs the developing master oscillator of the fetus. Experimental studies have shown that disturbed maternal circadian rhythms, referred to as chronodisruption, and perturbed melatonin cycles have negative consequences for the maturing fetal oscillators, which may lead to psychological and behavioral problems in the newborn. To optimize regular circadian rhythms and prevent disturbances of the melatonin cycle during pregnancy, shift work and bright light exposure at night should be avoided, especially during the last trimester of pregnancy. Finally, melatonin synergizes with oxytocin to promote delivery of the fetus. Since blood melatonin levels are normally highest during the dark period, the propensity of childbirth to occur at night may relate to the high levels of melatonin at this time which work in concert with oxytocin to enhance the strength of uterine contractions. CONCLUSIONS: A number of conclusions naturally evolve from the data summarized in this review: (i) melatonin, of both pineal and placental origin, has essential functions in fetal maturation and placenta/uterine homeostasis; (ii) circadian clock genes, which are components of all cells including those in the peripheral reproductive organs, have important roles in reproductive and organismal (fetal and maternal) physiology; (iii) due to the potent antioxidant actions of melatonin, coupled with its virtual absence of toxicity, this indoleamine may have utility in the treatment of pre-eclampsia, intrauterine growth restriction, placental and fetal ischemia/reperfusion, etc. (iv) the propensity for parturition to occur at night may relate to the synergism between the nocturnal increase in melatonin and oxytocin.

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Crossref · 10.1093/humupd/dmt054

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  • In humans, melatonin and dopamine receptors appear as early as gestational week 18 in the fetal SCN, suggesting melatonin and dopamine may serve as the primary communicators of circadian information for the fetus.

    “In humans, melatonin and dopamine receptors appear as early as gestational week 18 in the fetal SCN26–28, suggesting melatonin and dopamine may serve as the primary communicators of circadian information for the fetus29,30.”

    From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [30]

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Authors
Reiter, R. J., Tan, D. X., Korkmaz, A., & Rosales-Corral, S. A.
Affiliations
The University of Texas at San Antonio Health Science Center (US)
Corresponding author
Reiter, Russel J.
ORCID
Venue
Human Reproduction Update
Publisher
Oxford University Press (OUP)
Published
2013-10-16
Volume
20
Issue
2
Pages
293-307
ISSN
  • 1355-4786 (ISSN-L)
  • 1460-2369
DOI
10.1093/humupd/dmt054
OpenAlex
W2135819461
Cited by
371
References
205
Citations by year
2026: 24 · 2025: 42 · 2024: 30 · 2023: 47 · 2022: 44 · 2021: 31 · 2020: 35 · 2019: 35 · 2018: 27 · 2017: 20 · 2016: 16 · 2015: 12 · 2014: 7
FWCI
1.39
Type
journal article
Language
en
Open access
closed
Locations
  • Human Reproduction Update (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords
melatonin, circadian rhythm, pregnancy, placenta, fetal development, oxidative stress, free radicals, preeclampsia, fetal growth restriction, suprachiasmatic nucleus, circadian rhythm disruption, sleep-wake cycle, shift work, oxytocin, maternal-fetal communication, antioxidant activity, maternal health, fetal hypoxia
MeSH terms
Animals, Antioxidants, Biological Clocks, Circadian Rhythm, Female, Fetus, Humans, Mammals, Melatonin, Placenta, Pre-Eclampsia, Pregnancy, Uterus, Oxidative Stress, Parturition, Mice

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