Environmental hypoxia adversely affects reproductive health in humans and animals at high altitudes. Therefore, how to alleviate the follicle development disorder caused by hypoxia exposure and to improve the competence of fertility in plateau non-habituated female animals are important problems to be solved urgently. In this study, a hypobaric hypoxic chamber was used for 4 weeks to simulate hypoxic conditions in female mice, and the effects of hypoxia on follicle development, proliferation and apoptosis of granulosa cells, reactive oxygen species (ROS) levels in MII oocyte and 2-cell rate were evaluated. At the same time, the alleviating effect of melatonin on hypoxic exposure-induced oogenesis damage was evaluated by feeding appropriate amounts of melatonin daily under hypoxia for 4 weeks. The results showed that hypoxia exposure significantly increased the proportion of antral follicles in the ovary, the number of proliferation and apoptosis granulosa cells in the follicle, and the level of ROS in MII oocytes, eventually led to the decline of oocyte quality. However, these defects were alleviated when melatonin was fed under hypoxia conditions. Together, these findings suggest that hypoxia exposure impaired follicular development and reduced oocyte quality, and that melatonin supplementation alleviated the fertility reduction induced by hypoxia exposure.

Despite previous research demonstrating the benefits of including growth factors and antioxidants to maturation medium to support embryo production, to date the effect of epidermal growth factor (EGF) and melatonin (Mel) on oocyte competency has not been studied. This study supplemented in vitro maturation (IVM) medium with EGF (10 ng/ml) and Mel (50 ng/ml) alone, or in combination, and evaluated cumulus cell (CC) gene expression and the development and quality of parthenogenetic blastocysts. No differences in CC gene expression levels indicative of developmental potential were found among the treatment groups. Antioxidant gene CuZnSOD was significantly (P < 0.05) decreased in CCs from the Mel group. Moreover, blastocyst rates on day 7 were significantly increased in EGF or Mel (P < 0.05), but not EGF+Mel. Significant decrease (P < 0.05) in GPX1, CuZnSOD, SLC2A1 and HSPA1A (P = 0.07) mRNA levels was observed in blastocysts from the Mel group. OCT4 gene expression was significantly increased (P < 0.05) in EGF+Mel and confirmed using immunofluorescence. Our results indicate that, despite the lack of changes of competence-related genes in CCs, IVM medium supplemented with Mel improved the culture environment sufficiently, resulting in improved blastocysts. Moreover, EGF and Mel combined during maturation increased OCT4 gene and protein expression in blastocysts, indicating its potential for stem cells.

There is increasing evidence that glioblastoma, a highly aggressive brain tumour, originates from a neural stem cell (NSC) located in the subventricular zone (SVZ) of the lateral cerebral ventricle. Using the most advanced in vivo imaging techniques, Gengatharan and colleagues recently identified a day/night difference in the adult SVZ-NSC division. They reported that the circadian melatonin rhythm and its receptor control the day/night difference in NSC division with high mitotic activity during the day and low activity at night. Expression of melatonin and its receptor diminishes during ageing, which eliminates the regulatory effect of melatonin on NSC mitosis. Moreover, the circadian melatonin rhythm is dampened by light-at-night with the potential of altering the circadian mitotic cycle of NSC in the SVZ. Also, men with a lower melatonin amplitude than women exhibit a 60% higher rate of glioblastoma incidence. Given that ageing contributes significantly to glioblastoma initiation and progression, we suggest that the decline in circadian melatonin synthesis and release as well as its receptors in the SVZ, which also diminish with an ageing act in concert with other factors to facilitate glioblastoma initiation and growth.

To explore whether embryo culture with melatonin (MT) can improve the embryonic development and clinical outcome of patients with repeated cycles after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) failure, immature oocytes from controlled ovarian superovulation cycles were collected for in vitro maturation (IVM) and ICSI. The obtained embryos were cultured in 0, 10–11, 10–9, 10–7 and 10–5 M MT medium respectively, and 10–9 M was screened out as the optimal concentration. Subsequently, 140 patients who underwent failed IVF/ICSI cycles received 140 cycles of embryo culture in vitro with a medium containing 10–9 M MT, these 140 MT culture cycles were designated as the experimental group (10–9 M group), and the control group was the previous failed cycles of patients (0 M group). The results showed that the fertilization, cleavage, high-quality embryo, blastocyst, and high-quality blastocyst rates of the 10–9 M group were significantly higher than those of the 0 M group (P < 0.01; P < 0.01; P < 0.0001; P < 0.0001; P < 0.0001). To date, in total, 50 vitrified-warmed cycle transfers have been performed in the 10–9 M group and the implantation rate, biochemical pregnancy rate and clinical pregnancy rate were significantly higher than those in the 0 M group (all P < 0.0001). Two healthy infants were delivered successfully and the other 18 women who achieved clinical pregnancy also had good examination indexes. Therefore the application of 10–9 M MT to embryo cultures in vitro improved embryonic development in patients with repeated cycles after failed IVF/ICSI cycles and had good clinical outcomes.

Trial registration: ChiCTR2100045552.

A total of 80% of fibromyalgia (FM) population have reported poor sleep. In this regard, the pineal gland, involved in circadian rhythm processes as a key neuroendocrine organ which mainly synthesises and secretes melatonin, has never been studied before in this population. Therefore, this study aimed to evaluate the parenchyma pineal volume and its relation to sleep hours, sleep quality index and melatonin level at night. A total of 50 participants, 30 women with FM and 20 healthy control women underwent cranial magnetic resonance imaging. The total pineal volume, cyst pineal volume and parenchyma pineal volume were manually calculated in cubic millimetres. Also, the total pineal volume was estimated using Hasehawa method. Parenchyma pineal volume was significantly correlated with sleep hours (p-value = 0.041) and nocturnal melatonin level (p-value = 0.027). Moreover, there was also a non-significant correlation between parenchyma pineal volume and sleep quality index (p-value = 0.055). Furthermore, a mean parenchyma pineal volume of 102.00 (41.46) mm³ was observed, with a prevalence of 29.60% cyst in FM group. This is the first study that has reported pineal gland volumes, cyst prevalence and correlative relationships between parenchyma pineal volume and sleep hours and melatonin levels in women with FM.

Tramadol is used worldwide and is listed in many medical guidelines to treat both acute and chronic pains. There is a growing evidence of abuse of tramadol in some African and West Asian countries. Tramadol has some side effects. The present study designed to follow up the treatment of the cellular responses which might be induced in the kidney of tramadol mice. Treated mice received daily injection of tramadol dose (125 μg/100 g b.wt) for 20 and 40 days. Other mice received tramadol for 40 days and then were divided into three groups: the first received distilled water, the second received Lagenaria siceraria, and the third received melatonin daily for 40 days. Both the daily injection of tramadol for 20 and 40 days resulted in radical, extensive, and severe alterations in the normal histological architecture of the kidney. Treatment with Lagenaria siceraria or melatonin after tramadol administration for a long-term, markedly changed the collagen content and other chemical components, that may reach nearly normal levels. Such findings propose that although tramadol has many cytological and histopathological side effects on the kidneys of male mice, the treatments via Lagenaria siceraria and melatonin have effective therapeutic impacts on the tramadol side effects.

To investigate the effects of dietary fibre on follicular atresia in pigs fed a high-fat diet, we fed thirty-two prepubescent gilts a basal diet (CON) or a CON diet supplemented with 300 g/d dietary fibre (fibre), 240 g/d soya oil (SO) or both (fibre + SO). At the 19th day of the 4th oestrus cycle, gilts fed the SO diet showed 112 % more atretic follicles and greater expression of the apoptotic markers, Bax and caspase-3, and these effects were reversed by the fibre diet. The abundance of SCFA-producing microbes was decreased by the SO diet, but this effect was reversed by fibre treatment. Concentrations of serotonin and melatonin in the serum and follicular fluid were increased by the fibre diet. Overall, dietary fibre protected against high fat feeding-induced follicular atresia at least partly via gut microbiota-related serotonin–melatonin synthesis. These results provide insight into preventing negative effects on fertility in humans consuming a high-energy diet.

Seasonal affective disorder (SAD) is a recurrent form of major depression, particularly occurring in the winter months with a generally spontaneous remission in spring/summer. The predictable nature of this condition provides a potentially unique opportunity to prevent recurrence in sufferers of SAD. The Cochrane Review discussed here examines the evidence for melatonin and agomelatine in preventing SAD, putting its findings into their clinical context.

The purpose of this chronoepidemiologic study was to investigate the time-relationships between the yearly variations in occurrence of violent suicide in Belgium and the yearly variations in various biochemical, metabolic and immune variables in the Belgian population. The weekly mean number of deaths due to violent suicide for all of Belgium for the period 1979–1987 was computed. Twenty-six normal volunteers had monthly blood samplings during one calendar year for assays of plasma L-tryptophan (L-TRP), competing amino acids (CAA), and melatonin levels, maximal [3H]paroxetine binding to platelets, serum total cholesterol, calcium, magnesium, and soluble interleukin-2 receptor concentrations, and number of CD4+ T, CD8+ T and CD20+ B lymphocytes. The annual rhythm in violent suicide rate is highly significantly synchronized with the annual rhythms in L-TRP, [3H]paroxetine binding, cholesterol, calcium, magnesium, CD20+ B cells, and CD4+/CD8+ ratio; the mean peak (violent suicide, [3H]paroxetine binding) or nadir (all other variables) occurs around 3 May. There were significant inverse time-relationships between the time series of violent suicide rate and L-TRP, L-TRP/CAA ratio, total cholesterol, calcium and magnesium, CD4+/CD8+ T cell ratio and number of CD20+ B cells. Maximal [3H]paroxetine binding to platelets was significantly and positively related to the time series of violent suicide. An important part (56.4%) of the variance in mean weekly number of violent suicide rate was explained by the time series of L-TRP, cholesterol and melatonin.

5-methoxypsoralen (5-MOP) stimulates pineal melatonin secretion, and a decrease in dark phase melatonin levels has been described in major depression. As exogenous melatonin has shown synchronizer properties, authors hypothesized that giving 5-MOP would have antidepressant properties.

Twenty-six inpatients meeting the criteria of major depressive disorders were enrolled in a four-week, double blind trial of 5-MOP versus amitriptyline. Clinical improvement was identical in both treatment groups but biological changes were different in each group: 5-MOP patients showed an early nocturnal surge of melatonin levels that was maintained at the fourth treatment week, while melatonin levels remained unchanged in patients treated with amitriptyline.

The clinical finding that depressive disorders are often associated with desynchronization of internal rhythms has encouraged the idea that resetting normal circadian rhythms may have antidepressant potential. Agomelatine, a naphthalene analog of melatonin, is both an agonist of human cloned melatonergic MT1 and MT2 receptors and a serotonin 5-HT2C receptor antagonist. Agomelatine combines zeitgeber (synchroniser of the circadian system) activity with neurotransmitter augmentation properties (enhances the levels of dopamine and noradrenaline in frontal cortex). The efficacy of agomelatine in treating depression has been shown in three short-term, pivotal, randomized, placebo–controlled studies. These studies have demonstrated agomelatine to be efficacious in Major Depressive Disorder at the standard dose of 25 mg/day, with the possibility of increasing doses to 50 mg/day in those patients with insufficient improvement. The number of adverse events during the treatment period was comparable to placebo. Four studies have shown the positive effect of agomelatine on sleep continuity and quality and shortening of sleep latency. Despite these promising data, further studies are needed to examine agomelatine's efficacy over a longer treatment period.