**6. The relationship between melatonin and oxidative stress**

Oxidative stress is a cell-damaging condition that can result from decreased antioxidants and/or increased production of reactive free radicals such as reactive oxygen species and/or reactive nitrogen species (ROS/RSN) [98, 99]. Increased free radical production causes cell damage, leading to an increase in various damage markers (MDA, 8-OhDH, TNF-alpha) [100, 101]. In many cases, the body protects the cell against the increase in oxidative stress by the regulation of antioxidant defense systems (GSH, SOD, CAT, GPx) [102–107]. If oxidative stress can be neutralized, there is usually no adverse contribution to disease pathology. If antioxidant defense induction is inadequate or absent, concomitant cellular and tissue damage often occurs. Some diseases can be directly caused by oxidative stress, but in most diseases, oxidative stress is a consequence and can often only be a secondary event [108–110]. However, it plays an important role in promoting additional tissue damage in most diseases. When oxidative stress is excessive, it can be prevented by using various substances that have antioxidant properties or suppressing oxidative stress to prevent cell damage [111, 112]. One of the substances used for this purpose is melatonin. As a result of various studies, it has been determined that melatonin reduces oxidative stress and protects the cell against oxidative damage. Some studies have stated that it prevents cell damage by improving MDA levels [113–116]. The effect of melatonin on reducing MDA occurs through several mechanisms. For example; Melatonin detoxifies a large number of free radicals such as peroxynitrite anion [117] and hydroxyl radical [118] detoxifies hydroxyl radical [119]. It has also been determined that peroxynitrous acid [120] cleans oxidizing particles such as nitric oxide [121] and thus prevents lipid peroxidation. Due to these effects, It has been reported that the effects of melatonin on oxidative stress are direct free radical scavenger and indirect antioxidant [122]. Again, as a result of studies, it was determined that Melatonin increased the level of antioxidant GSH, and also caused an increase in antioxidant enzyme activities such as GPX, SOD, and CAT. It has been determined that these effects are caused by an increase in mRNA expression by stimulating the melatonin receptors on the cell membrane [123]. It has also been determined that melatonin inhibits the nuclear translocation of NF-κB [124]. It has been determined that melatonin inhibits oxidative stress-induced DNA damage by suppressing oxidative stress [125]. Studies have shown that melatonin inhibits apoptosis by decreasing caspase-3 activity and activating the PI3K/AKT pathway, and it preserves membrane integrity. Activation of the PI3K/AKT pathway also increases gene expression such as Nrf2 [126], which plays an important role in the antioxidant defense system. These findings explain the cellprotective mechanism of melatonin against oxidative stress.

## **7. Conclusion**

Melatonin is a hormone mainly synthesized from the pineal gland, and it has been shown by some studies that it has various effects on the immune system, oxidative stress, and reproduction, as well as taking part in the regulation of circadian rhythm. In this study, we focused on the direct, indirect, and antioxidant effects of melatonin on the female and male reproductive systems and the molecular mechanisms of these effects. As a result, melatonin affects the male and female reproductive systems directly via the gonads via secondary messengers and indirectly by stimulating various receptors/molecules via the hypothalamus-pituitary axis. These effects are in the direction of supporting reproduction in some living things and suppressing in others. In addition, melatonin prevents cell damage by increasing antioxidant enzyme activity and scavenging free radicals, especially in female and male gonads, thus preventing cell damage.

*An Overview of Effects on Reproductive Physiology of Melatonin DOI: http://dx.doi.org/10.5772/intechopen.108101*
