Bioactive Compounds Protect Mammalian Reproductive Cells from Xenobiotics and Heat Stress-Induced Oxidative Distress via Nrf2 Signaling Activation: A Narrative Review.

Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body's antioxidant defenses. It poses a significant threat to the physiological function of reproductive cells. Factors such as xenobiotics and heat can worsen this stress, leading to cellular damage and apoptosis, ultimately decreasing reproductive efficiency. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway plays a crucial role in defending against oxidative stress and protecting reproductive cells via enhancing antioxidant responses. Dysregulation of Nrf2 signaling has been associated with infertility and suboptimal reproductive performance in mammals. Recent advancements in therapeutic interventions have underscored the critical role of Nrf2 in mitigating oxidative damage and restoring the functional integrity of reproductive cells. In this narrative review, we delineate the harmful effects of heat and xenobiotic-induced oxidative stress on reproductive cells and explain how Nrf2 signaling provides protection against these challenges. Recent studies have shown that activating the Nrf2 signaling pathway using various bioactive compounds can ameliorate heat stress and xenobiotic-induced oxidative distress and apoptosis in mammalian reproductive cells. By comprehensively analyzing the existing literature, we propose Nrf2 as a key therapeutic target for mitigating oxidative damage and apoptosis in reproductive cells caused by exposure to xenobiotic exposure and heat stress. Additionally, based on the synthesis of these findings, we discuss the potential of therapies focused on the Nrf2 signaling pathway to improve mammalian reproductive efficiency.

Fatty acid composition and metabolic pathways in Arbacia dufresnii (Arbaciidae: Arbacioida) gametes: implications of shrimp byproducts in aquaculture feeds / Composición de ácidos grasos y vías metabólicas en los gametos de Arbacia dufresnii (Arbaciidae: Arbacioida) implicaciones de los subproductos de langostinos en los alimentos de acuicultura

Abstract Introduction: Care towards nutrition is essential for the quality of a sustainable aquaculture product. Since the balance in food affects the growth and production of gametes. The circular economy is made possible through the use of discarded materials. Objective: The aim of this research was to study the fatty acid composition and metabolic pathways in the gametes of Arbacia dufresnii, with a focus on the implications of incorporating shrimp byproducts into aquaculture feeds. Methods: Four different treatments were designed to maintain optimal nutritional quality, particularly in lipids and proteins, based on previous studies. The fatty acid profiles of the feeds and gametes were analyzed by using gas-chromatography, and statistical analyses were conducted to determine significant differences. Results: Significant differences were observed in the abundance (%) of omega-3 (ω-3) and omega-6 (ω-6) fatty acids. The (ω-3) metabolic pathway was more pronounced in the gametes of wild animals and those fed with the experimental feeds. In contrast, the (ω-6) metabolic pathway was less relevant in these groups. The (ω-3) /(ω-6) ratio was highest in the gametes of wild animals. Feeds enriched in fatty acids enhanced their bioaccumulation in the gametes reaching higher concentrations than wild animals. The availability of fatty acids in foods allowed their bioaccumulation in gametes, with concentrations equal to or higher than those observed in animals in their natural environment for certain fatty acids. Conclusions: Incorporating shrimp byproducts in aquaculture feeds demonstrated a promising strategy for resource utilization and organic input generation. The fatty acid composition in the gametes of A. dufresnii was influenced by the diet, highlighting the potential of balanced feeds to enhance the bioaccumulation of essential fatty acids. These findings provide valuable insights for the development of sustainable aquaculture practices and the production of nutritionally enriched seafood products.

Resumen Introducción: El cuidado hacia la nutrición es fundamental para la calidad de un producto acuícola sostenible. Ya que el balance en los alimentos afecta el crecimiento y producción de los gametos. A partir del aprovechamiento de materias de descarte se posibilita la economía circular. Objetivo: El objetivo de este estudio fue investigar la composición de ácidos grasos y las vías metabólicas en los gametos de Arbacia dufresnii, centrándose en las implicaciones de la incorporación de subproductos de camarones en los alimentos de acuicultura. Métodos: Se diseñaron cuatro tratamientos diferentes para mantener una calidad nutricional óptima, especialmente en lípidos y proteínas, basándose en estudios previos. Se analizaron los perfiles de ácidos grasos de los alimentos y los gametos mediante cromatografía de gases, y se realizaron análisis estadísticos para determinar diferencias significativas. Resultados: Se observaron diferencias significativas en la abundancia (%) de ácidos grasos omega-3 (ω-3) y omega-6 (ω-6). La vía metabólica de (ω-3) fue más pronunciada en los gametos de los animales en su entorno natural y aquellos alimentados con los piensos experimentales. Por el contrario, la vía metabólica de (ω-6) tuvo menos relevancia en estos grupos. La relación (ω-3) /(ω-6) fue más alta en los gametos de los animales en su entorno natural. La disponibilidad de ácidos grasos en los alimentos permitió su bioacumulación en los gametos, con concentraciones iguales o superiores a las observadas en los animales en su entorno natural para ciertos ácidos grasos. Conclusiones: La incorporación de subproductos de camarones en los alimentos de acuicultura demostró ser una estrategia prometedora para la utilización de recursos y la generación de insumos orgánicos. La composición de ácidos grasos en los gametos de A. dufresnii fue influenciada por la dieta, destacando el potencial de los alimentos balanceados para mejorar la bioacumulación de ácidos grasos esenciales. Estos hallazgos brindan información valiosa para el desarrollo de prácticas sostenibles en acuicultura y la producción de productos marinos enriquecidos nutricionalmente.

Advancements in Genetic Biomarkers and Exogenous Antioxidant Supplementation for Safeguarding Mammalian Cells against Heat-Induced Oxidative Stress and Apoptosis.

Heat stress represents a pervasive global concern with far-reaching implications for the reproductive efficiency of both animal and human populations. An extensive body of published research on heat stress effects utilizes controlled experimental environments to expose cells and tissues to heat stress and its disruptive influence on the physiological aspects of reproductive phenotypic traits, encompassing parameters such as sperm quality, sperm motility, viability, and overall competence. Beyond these immediate effects, heat stress has been linked to embryo losses, compromised oocyte development, and even infertility across diverse species. One of the primary mechanisms underlying these adverse reproductive outcomes is the elevation of reactive oxygen species (ROS) levels precipitating oxidative stress and apoptosis within mammalian reproductive cells. Oxidative stress and apoptosis are recognized as pivotal biological factors through which heat stress exerts its disruptive impact on both male and female reproductive cells. In a concerted effort to mitigate the detrimental consequences of heat stress, supplementation with antioxidants, both in natural and synthetic forms, has been explored as a potential intervention strategy. Furthermore, reproductive cells possess inherent self-protective mechanisms that come into play during episodes of heat stress, aiding in their survival. This comprehensive review delves into the multifaceted effects of heat stress on reproductive phenotypic traits and elucidates the intricate molecular mechanisms underpinning oxidative stress and apoptosis in reproductive cells, which compromise their normal function. Additionally, we provide a succinct overview of potential antioxidant interventions and highlight the genetic biomarkers within reproductive cells that possess self-protective capabilities, collectively offering promising avenues for ameliorating the negative impact of heat stress by restraining apoptosis and oxidative stress.

Omega-Class Glutathione Transferases Protect DNA from Oxidative Stress in Pathogenic Helminth Reproductive Cells.

Pathogenic helminths have evolved mechanisms to preserve reproductive function while surviving long-term in the host via robust protective responses. A protective role of antioxidant enzymes in preventing DNA degradation has long been proposed, but little evidence has been provided. Here, we show that omega-class glutathione transferases (GSTOs) are critical for maintaining viability by protecting the reproductive cell DNA of the carcinogenic liver fluke, Clonorchis sinensis. Clonorchis sinensis GSTO (CsGSTO) activities modified by changes in the GSH/GSSG and NADPH/NADP+ molar ratios suppressed the overproduction of reactive oxygen species. CsGSTO1 and CsGSTO2 catalyzed deglutathionylation under physiologic and low-stress conditions (GSH/GSSG ratio of 6:1 or higher) but promoted glutathionylation under high-stress conditions (GSH/GSSG ratio of 3:1 or lower). Gliotoxin-induced functional disruption of CsGSTOs in living C. sinensis reduced the GSH/GSSG molar ratio and increased the production of protein glutathionylation (PSSG) under physiologic and low-stress conditions, indicating that suppression of GSTO function did not affect deglutathionylation. However, the perturbation of CsGSTOs decreased the GSH/GSSG ratio but also reduced PSSG production under high oxidative stress, demonstrating that glutathionylation was impeded. In response to oxidative stimuli, C. sinensis decreased GSTO-specific dehydroascorbate reductase and thiol transferase activities and the GSH/GSSG ratio, while it increased the NADPH/NADP+ ratio and PSSG. CsGSTOs utilized GSH to regulate GSH/GSSG and NADPH/NADP+ recycling and triggered a redox signal leading to nuclear translocation. Nuclear-imported CsGSTOs were modified by glutathionylation to prevent DNA damage. Antibodies specific to CsGSTOs dose-dependently inhibited this process. Disruption of CsGSTOs or the depletion of GSH caused glutathionylation defects, leading to DNA degradation. Our results demonstrate that CsGSTOs and the GSH system play a previously unappreciated role in protecting DNA from oxidative stress.

Different Dynamics of Reproductive Cell Development in Oviparous Clausilia bidentata and Ovoviviparous Ruthenica filograna Snails.

Most terrestrial snails are oviparous and only some are ovoviviparous. The physiology of the reproductive system and its activity in these two groups have received little attention. We compared the month-to-month dynamics of reproductive cell formation between two species of Clausiliidae snails: Ruthenica filograna (an ovoviviparous species) and Clausilia bidentata (an oviparous species). Our aim was to test the hypothesis that the seasonal activity of gametogenesis is determined by reproductive strategy (oviparity /ovoviviparity). The results showed that the frequency and number of reproductive cells in different stages varied month-to-month, within each species, and between the two species. Ruthenica filograna maintained its reproductive activity throughout the entire observation period, whereas the gonadal activity of C. bidentata changed with the seasons (it was temperature dependent). Our results are in tune with the hypothesis of Baur, that ovovivipary has some advantage over oviparity under harsher environmental conditions.

Identification and Functional Analysis of MAPKAPK2 in Hyriopsis cumingii.

MAPKAPK2 (MK2) is an important regulator of the p38 mitogen-activated protein kinase (p38 MAPK) pathway, which is involved in a plethora of cellular processes concluding the development of gamete cells in meiosis and resisting pathogenic bacterial infestation. Hyriopsis cumingii is a significant mussel resource in China and a good material for pearl breeding. To explore the role of MK2 in H. cumingii, MK2 was identified and cloned, whose full-length cDNA was 1568 bp, including 87 bp in 5' UTR, 398 bp in 3' UTR, and 1083 bp in the open reading frame (ORF) region, encoding 360 amino acids. The expression of MK2 was the highest in the gills. Meanwhile, there was a significant difference in the gonads. After Aeromonas hydrophila and Lipopolysaccharide (LPS) infestation, the transcript level of the MK2 was upregulated in the gills. It indicated that MK2 might be involved in the innate immune response of H. cumingii after a pathogenic attack. After quantifying H. cumingii of different ages, it was found that the expression of MK2 was highest at 1 year old. In situ hybridization (ISH) results showed that the blue-purple hybridization signal was very significant in the oocytes and egg membranes of the female gonads of H. cumingii. The expression of MK2 increased gradually at the age of 1 to 5 months and showed a downward trend at the age of 5 to 8 months. It was suggested that MK2 might play an important role in the formation of primitive germ cells in H. cumingii. To sum up, MK2 might not only be involved in the immune response against pathogenic bacterial infection but also might play an important role in the development of the gonads in H. cumingii.

Influence of Acoustic-Mechanical Impact on the Reproductive Qualities of Sturgeon Sperm during Cryopreservation.

The use of various types of stimulation of fish spermatozoa in order to increase the survival of defrosted cells is a promising direction in the field of low-temperature preservation. In this work, the use of acoustic-mechanical effects on the sperm of sturgeons (in particular, sterlet) was studied for the first time. The technical characteristics of the assembled experimental device for acoustic-mechanical effects on fish sperm are given. As a result of this work, the optimal parameters of exposure to increase the preservation of defrosted germ cells were selected.

Cell-Specific Expression Pattern of Toll-Like Receptors and Their Roles in Animal Reproduction.

Toll-like receptors (TLRs), a part of the innate immune system, have critical roles in protection against infections and involve in basic pathology and physiology. Secreted molecules from the body or pathogens could be a ligand for induction of the TLR system. There are many immune and non-immune types of cells that express at a least single TLR on their surface or cytoplasm. Those cells may be a player in a defense system or in the physiological regulation mechanisms. Reproductive tract and organs contain different types of cells that have essential functions such as hormone production, providing an environment for embryo/fetus, germ cell production, etc. Although lower parts of reproductive organs are in a relationship with outsider contaminants (bacteria, viruses, etc.), upper parts should be sterile to provide a healthy pregnancy and germ cell production. In those areas, TLRs bear controller or regulator roles. In this chapter, we will provide current information about physiological functions of TLR in the cells of the reproductive organs and tract, and especially about their roles in follicle selection, maturation, follicular atresia, ovulation, corpus luteum (CL) formation and regression, establishment and maintenance of pregnancy, sperm production, maturation, capacitation as well as the relationship between TLR polymorphism and reproduction in domestic animals. We will also discuss pathogen-associated molecular patterns (PAMPs)-induced TLRs that involve in reproductive inflammation/pathology.

Sodium arsenite-induced detriment of cell function in Leydig and Sertoli cells: the potential relation of oxidative damage and antioxidant defense system.

Arsenic is commonly found in the natural environment and is toxic agent for living organism in many countries in the world. Studies on animal models suggest that exposure to arsenic may cause reproductive toxicity; however, effect of arsenic on reproductive toxicity has still not been clearly described. This study was focused on cytotoxicity, oxidative stress, and the antioxidant defense system induced with exposure to sodium arsenite in Mus musculus Leydig and Sertoli cells. The cells were exposed to two different concentrations of sodium arsenite of 50 ppb (0.4 µM) and 1000 ppb (7.7 µM) for 24, 48, and 72 h. Following the exposure time, cell viability, cell proliferation, and lactate dehydrogenase (LDH) activity were determining using colorimetric method. Also, we evaluated oxidative stress markers such as glutathione (GSH), lipid peroxidation, hydroxyl radical, hydrogen peroxide levels, and cellular enzymatic antioxidants such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-s-transferase, and γ-glutamyl transpeptidase (γ-GT). As a result, sodium arsenite exposure in Leydig and Sertoli cells caused cellular cytotoxicity and downregulated the antioxidant defense system by inducing oxidative stress depending on concentration and time. Furthermore, this study demonstrated that when compared with Sertoli cells, Leydig cells were more affected by arsenite toxicity.

Reproductive function: the protection of the rights of the people which are sent to the area of the fighting.

OBJECTIVE: Introduction: The issues of problems of the legal regulation of posthumous reproduction in Ukraine and foreign countries are analysis in the article. The author substantiates the necessity in the creation and acceptance of the State Program of the retrieval of reproductive cells in people who are sending to the area of the fighting. The aim:the purpose of our work is a comprehensive study of post-mortem (post-mortem) reproduction and substantiation of the possibility and necessity of adopting a state program for the selection of reproductive cells of individuals who are sent to a combat zone to ensure their full social protection and assistance in the realization of the right to fatherhood or motherhood. PATIENTS AND METHODS: Materials and methods: the experience of certain countries is analyzed in the research. Additionally, we used statistical data of international organizations, conclusions of experts and foreign legal acts dealing with posthumous reproduction and auxiliary reproductive technologies, judicial practice, doctrinal ideas and views on this issue. RESULTS: Review: there are medical (practical) preconditions for the introduction of posthumous reproduction programs. Among them is the technology of obtaining reproductive cells (post-mortem too), their preservation and successful subsequent use. In addition, foreign experience shows the success of the application of these technologies and the real guarantee of full implementation of the range of rights to the family, fatherhood or maternity. CONCLUSION: Conclusions: we note the urgent need to develop and adopt a state reproductive cell selection program for individuals who are sent to the combat zones (according to a model that exists in such countries as the USA and Israel).

Sublethal effects of zinc oxide nanoparticles on male reproductive cells.

Environmental exposure to nanomaterials is inevitable as nanomaterials become part of our daily life, and as a result, nanotoxicity research is gaining attention. Most investigators focused on the effects of zinc oxide nanoparticles (ZnO NPs) on human health, while limited information was available on the male reproductive system. Herein, mouse Sertoli cell line (TM-4) and spermatocyte cell line (GC2-spd) were used as in vitro models to explore the reproductive effects of ZnO NPs at sublethal dose and its underlying mechanisms. Cells were treated with different concentrations of ZnO NPs. By cell viability assay, a dose of 8µg/mL was found as a sublethal dose and increased the ROS levels in both cells. The decreased glutathione level and increased MDA level were also found in ZnO NPs treated group. In TM4 cells, the expressions of BTB proteins (ZO-1, occludin, claudin-5, and connexin-43) were lower in the ZnO NPs group. The increased cell permeability and increased TNF-α secretion were also observed in ZnO NPs group. In GC2-spd cells, S phase arrest and DNA damage occurred in ZnO NPs group, which could be partially rescued by NAC. Our findings demonstrated that exposure to ZnO NPs induced ROS generation, caused DNA damage of germ cells, and down-regulated the expression of BTB proteins in Sertoli cells which could compromise the integrity of the blood-testis barrier. All these contributed to the male reproductive cytotoxic effects of ZnO NPs that could be partially rescued by anti-oxidants.