Melatonin, Clock Genes, and Mammalian Reproduction: What Is the Link?

Amnon Brzezinski,Seithikurippu R Pandi-Perumal,Adyasha Purohit,Seema Rai

doi:10.3390/ijms222413240

Abstract

Physiological processes and behaviors in many mammals are rhythmic. Recently there has been increasing interest in the role of circadian rhythmicity in the control of reproductive function. The circadian rhythm of the pineal hormone melatonin plays a role in synchronizing the reproductive responses of animals to environmental light conditions. There is some evidence that melatonin may have a role in the biological regulation of circadian rhythms and reproduction in humans. Moreover, circadian rhythms and clock genes appear to be involved in optimal reproductive performance. These rhythms are controlled by an endogenous molecular clock within the suprachiasmatic nucleus (SCN) in the hypothalamus, which is entrained by the light/dark cycle. The SCN synchronizes multiple subsidiary oscillators (clock genes) existing in various tissues throughout the body. The basis for maintaining the circadian rhythm is a molecular clock consisting of transcriptional/translational feedback loops. Circadian rhythms and clock genes appear to be involved in optimal reproductive performance. This mini review summarizes the current knowledge regarding the interrelationships between melatonin and the endogenous molecular clocks and their involvement in reproductive physiology (e.g., ovulation) and pathophysiology (e.g., polycystic ovarian syndrome).

Highlights

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The circadian rhythm of melatonin synthesis in the pineal gland is involved in the regulation of mammalian reproduction [1,2,3,4]
Substantial concentrations of melatonin were found in ovarian follicular fluids [12], and melatonin receptors were reported in ovarian granulosa cells [13]

Summary

Melatonin and Reproduction

The circadian rhythm of melatonin synthesis in the pineal gland is involved in the regulation of mammalian (including humans) reproduction [1,2,3,4]. The circulating plasma levels of melatonin are relatively high in childhood and decrease significantly during puberty. These discrepancies have led to skepticism among clinicians regarding the importance of melatonin in normal pubertal development In both young males and females, the puberty-related decline of high childhood melatonin levels has been correlated more to advancing Tanner stages than to chronological age [21]; no clear causative basis for this relationship has been established for humans. Hobson et al [28] reported modest improvements in the duration of pregnancy in a small study of women with preeclampsia who received 10 mg oral melatonin three times a day These preliminary results may suggest new therapeutic possibilities to improve clinical outcomes for women with preeclampsia. Clinical experience related to this issue has yielded inconclusive and sometimes conflicting results [4,29]; further clinical studies are warranted

Molecular Clock Genes

Clock Genes and Reproduction

Melatonin—Clock Genes Interactions

Findings

Conclusions