Melatonin and human reproduction

“How can one molecule have so much influence on health and well-being?”

This is the question that Prof. J Russel Reiter has asked himself during his melatonin research. Part of the answer is that melatonin is an ancient molecule found in all the living organisms over the evolution; this means it is essential to life.
In all the life-forms in which it has been studied, the hormone has been produced in the same circadian rhythm, with higher levels produced at night than during the daytime.

In this article we focus our attention to the diverse and essential role of melatonin in human reproduction, for both fertility and pregnancy period.

Melatonin and ovulation:

The human preovulatory follicular fluid (FF) contains concentrations of melatonin three-fold higher than in plasma and melatonin receptors are present in ovarian granulosa cells (GC).

During the oocyte maturation melatonin trains several functions: at the beginning it supports the steroidogenesis, regulating the production of both Testosterone and Estrogens; activates several anti-apoptotic molecules and finally induces the expression of LH receptors on the GC.

Finally, ovulation has been likened to an inflammatory reaction, characterized by elevated production of prostaglandins and cytokines, the increased action of proteolytic enzymes and the heightened permeability of small blood vessels in the follicular wall. These changes are associated with the generation of reactive oxygen species by macrophages, neutrophils, and endothelial cells, which also contribute to the disintegration of the follicular wall to allow the escape of the oocyte.  Although ROS may actually aid the oocyte maturation and follicular rupture to permit its extrusion, an excessive level of free radicals would surely damage this critically important cell. Therefore, a delicate balance must be maintained in the follicle to ensure successful maturation of the oocyte and timely follicular rupture. The presence of melatonin, a proven antioxidant, in the ovary likely helps maintain this balance, preserving DNA damage.

Melatonin into the Placenta:

Placenta possesses Melatonin receptors (MT1 and MT2) and furthermore it is able to produce itself melatonin, at levels 10.000 times superior to the pituitary gland. The first action mediated by melatonin receptors is to ensure the successful maintenance of the syncytiotrophoblasts (STB) by preventing the apoptosis of vCTB. This morphogenic action of melatonin aids in ensuring optimal placental function and successfully maintains pregnancy.
Through this action, melatonin showed preventing the progression of preeclampsia.

Melatonin and the fetal clock:

Data showed that melatonin is rapidly transferred from the maternal to the fetal circulation; so fetal melatonin levels, as well as its rhythm, are similar to the maternal ones.

In the fetus, the suprachiasmatic nucleus (SCN) is morphologically identifiable in the hypothalamus by mid-gestation. The maturation of the rhythmic expression of the fetal SCN seems to depend on information received from the mother. This rhythm may play an essential role in determining the organization and functional architecture of the developing fetal SCN.


Melatonin literature is vast and growing, and its role in human reproduction, such as in other clinical fields, continues to be a surprising discovery.


1. Melatonin and the ovary: physiological and pathophysiological implications Tamura et al. Fertil Steril 2009.

  1. Human placental trophoblasts synthesize melatonin and express its receptors. Lanoix et al. J. Pineal Res. 2008.
  2. Melatonin and the circadian system: contributions to successful female reproduction. Reiter RJ and al. Fertil Steril. 2014.
  3. Melatonin and Female Reproduction: An Expanding Universe. Olcese JM. Front. Endocrinol. 2020
  4. Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging. Tamura et al. Int. J. Mol. Sci. 2020.