Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging

Abstract

Melatonin is probably produced in all cells but is only secreted by the pineal gland. The pineal secretion of melatonin is determined by the light-dark cycle, and it is only released at night. Melatonin regulates biological rhythms via its receptors located in the suprachiasmatic nuclei of the hypothalamus. Melatonin also has strong antioxidant activities to scavenge free radicals such as reactive oxygen species (ROS). The direct free radical scavenging actions are receptor independent. ROS play an important role in reproductive function including in the ovulatory process. However, excessive ROS can also have an adverse effect on oocytes because of oxidative stress, thereby causing infertility. It is becoming clear that melatonin is located in the ovarian follicular fluid and in the oocytes themselves, which protects these cells from oxidative damage as well as having other beneficial actions in oocyte maturation, fertilization, and embryo development. Trials on humans have investigated the improvement of outcomes of assisted reproductive technology (ART), such as in vitro fertilization and embryo transfer (IVF-ET), by way of administering melatonin to patients suffering from infertility. In addition, clinical research has examined melatonin as an anti-aging molecule via its antioxidative actions, and its relationship with the aging diseases, e.g., Alzheimer's and Parkinson's disease, is also underway. Melatonin may also reduce ovarian aging, which is a major issue in assisted reproductive technology. This review explains the relationship between melatonin and human reproductive function, as well as the clinical applications expected to improve the outcomes of assisted reproductive technology such as IVF, while also discussing possibilities for melatonin in preventing ovarian aging.

Melatonin Supplementation and Outcomes After Assisted Reproductive Technology: A Systematic Review and Meta-analyses

“…There were some possible explanations to our results as follows: 1) MT receptors (MTR) are present in granulosa cells, oocytes and embryos [14,20,21], which laid foundation for MT's function. 2) MT is amphiphilic, and it can easily pass through cell membranes [4]. 3) Both MT and its metabolites are terminal stable antioxidant, will not act as an oxidant in any case [22,23].…”

Melatonin and Autophagy in Aging-Related Neurodegenerative Diseases

“…A few reports have shown that melatonin exerts protective effects in several experimental models of PD [ 200 , 201 , 202 , 203 ]. For a long time, a chemical, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has been used as a tool to induce PD in animal models [ 204 ], since it is a neurotoxic and psychoactive agent [ 205 ].…”

Melatonin Inhibits Oxidative Stress and Apoptosis in Cryopreserved Ovarian Tissues via Nrf2/HO-1 Signaling Pathway

“…Some antioxidants (such as MLT and resveratrol) have been shown to counteract the negative effects of cryopreservation on the quantity and quality of OTs, probably through the enhancement of free radical scavenging mechanisms in the follicles ( Tarín et al, 2002 ; Rocha et al, 2018 ; Olcese, 2020 ). Therefore, antioxidants are required for elimination of ROS ( Tamura et al, 2020 ).…”

“…Melatonin (N-acetyl-5-methoxytryptamine), one of the most well-studied molecules in recent years, is mainly synthesized and secreted by pineal organ of animal and human. It acts as an antioxidant in several reproductive organs and can directly scavenge a variety of free radicals ( Reiter et al, 2016 ; Tamura et al, 2020 ). It also functions to upregulate antioxidant protein expression and to protect against oxidant-mediated damage in many cryopreserved sperm/tissues (human sperm and ovary) ( Li et al, 2009 ; Wang et al, 2012 ; Gao et al, 2016 ; Deng et al, 2017 ; Goodarzi et al, 2017 ).…”