Panacea Index Logo

Command Palette

Search for a command to run...

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

Human reproduction update
January 1, 2014
Russel J Reiter et al. (4 authors)
Journal ArticleReviewHuman Study
Study Details

Study Goal

The researchers aimed to summarize the relationship between melatonin, circadian rhythms, and reproductive health, particularly during pregnancy, and explore melatonin's potential therapeutic roles.

Results Summary

Melatonin and stable circadian rhythms positively impact reproduction, especially in pregnancy, by reducing oxidative stress and protecting placental and fetal health. Melatonin also synergizes with oxytocin to promote nighttime childbirth.

Population

Pregnant individuals and fetal development (primarily non-human mammals in experimental studies).

Effective Dosage

Not specified

Duration

Not specified

Interactions

None mentioned

Extracted Claims (9)
InterventionDirectionEndpointPopulationDosageImpactClaim #
melatonin
increase
peripheral reproductive organs
-
-
has beneficial actions
#1
stable circadian rhythms
increase
reproductive health
-
-
are helpful in maintaining
#2
melatonin
decrease
molecular mutilation and cellular dysfunction
ovary and placenta
-
protects against
#3
melatonin
decrease
free radical damage
non-human mammals
-
has ameliorated
#4
maintenance of a regular maternal light/dark and sleep/wake cycle
increase
circadian rhythms
mother
-
is important to stabilize
#5
disturbed maternal circadian rhythms (chronodisruption)
decrease
maturing fetal oscillators
fetus
-
have negative consequences for
#6
perturbed melatonin cycles
decrease
maturing fetal oscillators
fetus
-
have negative consequences for
#7
melatonin
increase
delivery of the fetus
-
-
synergizes with oxytocin to promote
#8
melatonin
increase
strength of uterine contractions
-
-
work in concert with oxytocin to enhance
#9
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.

Medical Subject Headings (MeSH)
AnimalsAntioxidantsBiological ClocksCircadian RhythmFemaleFetusHumansMammalsMelatoninMiceOxidative StressParturitionPlacentaPre-EclampsiaPregnancyUterus
Study Links
Quality Scores
Safety85
Efficacy80/10
Quality75/10
Citation Metrics
Total Citations198
Citations/Year18.0
Relative Citation Ratio8.17
NIH Percentile96.9%
Research Impact Scores
APT Score0.75
Weight Score0.92
Normalized Score0.81
Related Supplements