Reactive oxygen species (ROS) are mainly produced in mitochondria and are involved in various physiological activities of the ovary through signaling and are critical for regulating the ovarian cycle. Notably, the imbalance between ROS generation and the antioxidant defense system contributes to the development of ovarian diseases. These contradictory effects have critical implications for potential antioxidant strategies that aim to scavenge excessive ROS. However, much remains to be learned about how ROS causes various ovarian diseases to the application of antioxidant therapy for ovarian diseases. Here, we review the mechanisms of ROS generation and maintenance of homeostasis in the ovary and its associated physiological effects. Additionally, we have highlighted the pathological mechanisms of ROS in ovarian diseases and potential antioxidant strategies for treatment. 

https://doi.org/10.1016/j.redox.2023.102659

Reactive oxygen species and ovarian diseases: Antioxidant strategies

Melatonin is an indoleamine with crucial antioxidant properties that are used to combat inflammatory and neoplastic processes, as well as control transplants. However, the clinical applications of melatonin have not yet been fully consolidated in the literature and require in-depth analysis. Objectives: This study reviewed the literature on the antioxidant properties of melatonin in rat models. Methods: We followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses and used the PubMed, LILACS, and Cochrane databases, Google Scholar, and article references, irrespective of publication time. Results: Ten articles involving 485 rats were selected, and the effects of melatonin on antioxidant markers were investigated. Melatonin increased superoxide dismutase in nine studies, glutathione peroxidase in seven studies, and catalase in five studies. In contrast, melatonin reduced glutathione in three studies and malonaldehyde in seven of eight studies. Conclusion: Our findings suggest that melatonin effectively reduces oxidative stress.

Antioxidant Actions of Melatonin: A Systematic Review of Animal Studies

Spinach tends to deteriorate after harvest due to physiological metabolic activities. As a natural, pollution-free, and environmentally friendly preservative, melatonin (MT) can effectively maintain the quality of fruits and vegetables after harvest and delay senescence. To enhance the preservation effect of MT, this study developed antioxidant films using MT-loaded UiO-66 metal-organic framework (MOF) nanoparticles. This approach effectively extends the shelf life of spinach while preserving its quality. The underlying mechanism involves leveraging the microporous structure and stability of UiO-66 MOF. Experimental results obtained from the packaging films demonstrated significant improvements in both mechanical strength and antioxidant properties when UiO-66 was loaded with MT at a concentration of 0.20 mg/mL and combined with sodium alginate. Freshness preservation experiments also indicated the effective preservation effect of these films on spinach. In conclusion, the results of this study suggest that MT-loaded UiO-66 MOF is a promising active packaging material for spinach preservation. 

Development of packaging films based on UiO-66 MOF loaded melatonin with antioxidation functions for spinach preservation.

Decrease in quality of postovulatory aged oocytes occurs due to oxidative stress and leads to low fertilization and development competence. It is one of the main causes that exerting detrimental effect on the success rate in assisted reproductive technology (ART). Auraptene (AUR), a citrus coumarin, has been reported to possess an antioxidant effects in other tissues. In this study, we aimed to confirm the potential of AUR to delay the oocyte aging process by alleviating oxidative stress. Superovulated mouse oocytes in metaphase of second meiosis (MII) were exposed to 0, 1 or 10 μM AUR for 12 h of in vitro aging. AUR addition to the culture medium recovered abnormal spindle and chromosome morphology and mitigated mitochondrial distribution and mitochondrial membrane potential (ΔΨ) in aged oocytes. AUR-treated aged oocytes also showed suppressed oxidative stress, with lower reactive oxygen species (ROS) levels, higher glutathione (GSH) levels and increased expression of several genes involved in antioxidation. Furthermore, AUR significantly elevated the fertilization and embryo developmental rates. Oocytes aged with 1 μM AUR exhibited morphokinetics that were very similar to those of the control group. Altogether, these data allowed us to conclude that AUR improved the quality of aged oocytes and suggest AUR as an effective clinical supplement candidate to prevent postovulatory aging.

/pdf/the-antioxidant-auraptene-improves-aged-oocyte-quality-and-2cilaqj9.pdf

The Antioxidant Auraptene Improves Aged Oocyte Quality and Embryo Development in Mice

Nicotinamide adenine dinucleotide (NAD+), a crucial coenzyme in cellular redox reactions, is closely associated with age-related functional degeneration and metabolic diseases. NAD exerts direct and indirect influences on many crucial cellular functions, including metabolic pathways, DNA repair, chromatin remodeling, cellular senescence, and immune cell functionality. These cellular processes and functions are essential for maintaining tissue and metabolic homeostasis, as well as healthy aging. Causality has been elucidated between a decline in NAD levels and multiple age-related diseases, which has been confirmed by various strategies aimed at increasing NAD levels in the preclinical setting. Ovarian aging is recognized as a natural process characterized by a decline in follicle number and function, resulting in decreased estrogen production and menopause. In this regard, it is necessary to address the many factors involved in this complicated procedure, which could improve fertility in women of advanced maternal age. Concerning the decrease in NAD+ levels as ovarian aging progresses, promising and exciting results are presented for strategies using NAD+ precursors to promote NAD+ biosynthesis, which could substantially improve oocyte quality and alleviate ovarian aging. Hence, to acquire further insights into NAD+ metabolism and biology, this review aims to probe the factors affecting ovarian aging, the characteristics of NAD+ precursors, and the current research status of NAD+ supplementation in ovarian aging. Specifically, by gaining a comprehensive understanding of these aspects, we are optimistic about the prominent progress that will be made in both research and therapy related to ovarian aging. 

Impact of NAD+ metabolism on ovarian aging

Roles of melatonin in the field of reproductive medicine.

Hormesis describes a biphasic dose-response relationship generally characterized by a low-dose excitement and a high-dose inhibition This phenomenon has been observed in the regulation of cell, organ, and organismic level However, hormesis has not reported in oocytes In this study, we observed, for the first time, hormetic responses of PIPP levels in oocytes by inhibitor of Akt1 or PKCδ The expression of PIPP was detected by qPCR, immunofluorescent (IF), and Western Blot (WB) To observe the changes of PIPP levels, we used the inhibitors against pAkt1 (Ser473) or PKCδ, SH-6 or sotrastaurin with low and/or high-dose, treated GV oocytes and cultured for 4 h, respectively The results showed that PIPP expression was significantly enhanced when oocytes were treated with SH-6 or sotrastaurin 10 μM, but decreased with SH-6 or sotrastaurin 100 μM We also examined the changes of PIPP levels when GV oocytes were treated with exogenous PtdIns(3,4,5)P3 or LY294002 for 4 h Our results showed that PIPP level was enhanced much higher under the treatment of 01 μM PtdIns(3,4,5)P3 than that of 1 μM PtdIns(3,4,5)P3, which is consistent with the changes of PIPP when oocytes were treated with inhibitors of pAkt1 (Ser473) or PKCδ In addition, with PIPP siRNA, we detected that down-regulated PIPP may affect distributions of Akt, Cdc25, and pCdc2 (Tyr15) Taken together, these results show that the relationships between PIPP and Akt may follow the principle of hormesis and play a key role during release of diplotene arrest in mouse oocytes

Hormesis of low-dose inhibition of pAkt1 (Ser473) followed by a great increase of proline-rich inositol polyphosphate 5-phosphatase (PIPP) level in oocytes

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Roles of melatonin in the field of reproductive medicine.

Hormesis of low-dose inhibition of pAkt1 (Ser473) followed by a great increase of proline-rich inositol polyphosphate 5-phosphatase (PIPP) level in oocytes