Abstract
Decline in semen quality has become a global public health concern. Psychological stress is common in the current modern society and is associated with semen decline. Increasing evidence demonstrated that melatonin has anti-apoptotic and antioxidant functions. Whether melatonin can ameliorate the damage in testes induced by psychological stress has never been investigated. Here, a mouse model of restraint stress demonstrated that melatonin normalized the sperm density decline, testicular cells apoptosis, and testicular oxidative stress in stressed male mice. Melatonin decreased reactive oxygen species (ROS) level, increased superoxide dismutase (SOD) and glutathione (GSH) activities, and downregulated inducible nitric oxide synthase (iNOS) and tumor necrosis factor-α (TNF-α) activities in stressed mice testes. Furthermore, melatonin reduced the stress-induced activation of the NF-κB signaling pathway by decreasing the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) and p65 nuclear translocation. In addition, melatonin upregulated the expression of anti-oxidant proteins including nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Meanwhile, in vitro studies also demonstrated melatonin could reduce oxidative apoptosis of testicular cells. Collectively, melatonin mitigated psychological stress-induced spermatogenic damage, which provides evidence for melatonin as a therapy against sperm impairment associated with psychological stress.
Highlights
10–15% of couples are infertile worldwide, and the male counterpart affects 40–60% of infertility[1, 2]
Increasing evidence demonstrates that chronic stress, including restraint stress, results in a significant decline in the quality of semen[18,19,20], which could be related to a disruption in testosterone secretion in testes[20,21,22], and an increase of oxidative stress[20, 23, 24], and apoptosis of germ cells[19, 24, 25]
Given that the oxidative stress is a major contributor to restraint stress-induced spermatogenic damage that could lead to testicular cells apoptosis[24, 26, 27], we investigated the status of oxidative stress in the testes of each group and the level of reactive oxygen species (ROS) was evaluated
Summary
10–15% of couples are infertile worldwide, and the male counterpart affects 40–60% of infertility[1, 2]. Increasing evidence demonstrates that chronic stress, including restraint stress, results in a significant decline in the quality of semen[18,19,20], which could be related to a disruption in testosterone secretion in testes[20,21,22], and an increase of oxidative stress[20, 23, 24], and apoptosis of germ cells[19, 24, 25]. Few systematic studies have investigated whether melatonin exerts a protective role in the psychological stress-induced impairment of spermatogenesis as well as the mechanisms by which melatonin mitigates the damage in testes. In this study, we used a mouse model of restraint stress in order to investigate the effects of melatonin on stress-induced testicular cells apoptosis and oxidative stress and explored the mechanisms underlying the beneficial effects of melatonin
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