Peripheral reproductive organ health and melatonin: ready for prime time.


Reiter RJ, Rosales-Corral SA, Manchester LC, Tan DX




Int J Mol Sci. 2013 Apr 2;14(4):7231-72.

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Melatonin has a wide variety of beneficial actions at the level of the gonads and their adnexa. Some actions are mediated via its classic membrane melatonin receptors while others seem to be receptor-independent.

This review summarizes many of the published reports which confirm that melatonin, which is produced in the ovary, aids in advancing follicular maturation and preserving the integrity of the ovum prior to and at the time of ovulation. Likewise, when ova are collected for in vitro fertilization-embryo transfer, treating them with melatonin improves implantation and pregnancy rates.

Melatonin synthesis as well as its receptors have also been identified in the placenta. In this organ, melatonin seems to be of particular importance for the maintenance of the optimal turnover of cells in the villous trophoblast via its ability to regulate apoptosis.

For male gametes, melatonin has also proven useful in protecting them from oxidative damage and preserving their viability. Incubation of ejaculated animal sperm improves their motility and prolongs their viability. For human sperm as well, melatonin is also a valuable agent for protecting them from free radical damage.

In general, the direct actions of melatonin on the gonads and adnexa of mammals indicate it is an important agent for maintaining optimal reproductive physiology.

In the ovarian follicle, melatonin impacts the function of numerous cells, especially granulosa cells and the ovum (oocyte). The actions of melatonin in these cells are mediated via membrane receptors (MT1 and MT2) and also via binding sites in the nucleus and in the cytosol. In addition to its receptor-mediated actions, melatonin also functions as a direct free radical scavenger to reduce oxidative stress at the level of the ovary; this beneficial action is carried out without an interaction with a receptor. Additional antioxidant functions of melatonin are achieved when the indole stimulates enzymes which metabolize free radicals to less toxic products. The antioxidative enzymes include superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in thecal cells, granulosa cells and in the follicular fluid. The origin of melatonin in the follicular fluid is the blood and from its local synthesis in granulosa cells. (Source: modified according to Reiter RJ et al., 2013 and Tamura H et al., 2009)
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