Oxidative Stress in Human Reproduction Shedding Light on a Complicated Phenomenon
Abstract
This book discusses the role of oxidative stress in the reproductive system. The book reviews endogenous sources, methods of determining its levels in body fluid/tissues, the physiological roles of ROS, as well as its negative effects on the human reproductive processes. Also discussed are multiple extrinsic factors that could induce oxidative stress in the reproductive system. This volume covers various clinical pathologies related to the reproductive system that arise from or produce oxidative stress, both in the male and female. The use of antioxidants as a therapeutic measure to keep ROS levels in check are highlighted, describing the outcome of various clinical studies involving antioxidant supplementation in infertile patients. Infertility is a global disease that affects 15-25% of all couples, and oxidative stress arising from a multitude of sources has been implicated as one of the major contributing factors to the decline in human fertility. As such, this book provides an up-to-date review on the significance of ROS in human reproduction
Chapters (8)
Reactive oxygen species (ROS) are highly reactive molecules that are generated from oxygen metabolism. They can be free radicals or non-radicals. Free radicals are molecules that contain at least one unpaired valence electron at their outer shell, making them highly reactive and short lived [1]. Among all the ROS, superoxide anion (•O2−), hydrogen peroxide (H2O2) and hydroxyl radicals (•OH) are the most known examples. Reactive nitrogen species (RNS), is the subclass of ROS that contain nitrogen compound [2]. Both ROS and RNS, when present in physiological amount, have important roles in normal cellular functions such as fighting against infection, regulating different intercellular signaling pathways and facilitating normal maturation and fertilization in reproductive systems [1, 3–7]. However, when ROS present in high concentration, overwhelming the antioxidant defense system, oxidative stress results, and this may lead to cellular dysfunction via lipid peroxidation, protein and DNA damages [8]. Due to such damaging effect on the cells, OS is related to many pathological conditions including infertility [3, 9].
Reactive oxygen species (ROS) are produced by abnormal spermatozoa and white blood cells. They are highly unstable and difficult to measure. The end product of ROS are stable and easy to measure. High levels of ROS and low amounts of total antioxidants result in oxidative stress. High ROS levels can damage lipids, proteins and DNA in the cell. Accurate measurement of ROS or their end products is therefore important. This chapter describes various methods, both direct and indirect to measure ROS or their end products.
Reactive oxygen species (ROS) are highly reactive oxidizing agents which play certain physiological and pathological roles in the human body [1]. These substances are normally present within the cells. ROS are mostly free radicals. Free radicals have been labeled as molecular entities containing at least one unpaired electron which gives rise to a highly reactive group of compounds [2]. Moderate concentrations of ROS are vital in maintaining a number of physiologic processes in both male and female reproductive systems. ROS can be acquired through two different classes of sources, either endogenous (cellular) or exogenous. Unlike endogenous ROS, exogenous sources such as ultraviolet light, chemotherapeutic agents and inflammatory cytokines do not play a major role in generating ROS in the female reproductive system [3]. Endogenous sources, however, are the most prominent birthplace from which ROS are derived. The major intracellular sources of ROS include the electron transport chain in the mitochondria, endoplasmic reticulum as well as the peroxisomes [4]. Conversely, other extra-mitochondrial ROS sources exist through numerous enzymatic pathways. Examples include NADPH oxidase, xanthine oxidase, lipoxygenases, cyclooxygenases and the cytochrome P450 systems [5].
Oxidative stress (OS) has both physiological or positive as well as pathological or negative effects on the male and the female reproductive system. In the male, the negative effects of OS can be on the sperm parameters such as sperm concentration, motility, morpology, lipid peroxidation, acrosome reaction, spermoocte fusion etc. whereas in the female reproductive system it can effect follicular fluid, peritoneal fluid, hydrosalpingeal fluid as well as oocyte quality. These effects as well as the mechanism involved in this damage are discussed in this chapter.
Reactive oxygen species (ROS) are free radical and non-free radical oxidizing agents that play a normal physiological role in the body at low physiological amount [1]. Biological reactions and mitochondrial processes generate regular amounts of ROS. In the female reproductive system, ROS plays an essential role in signal transduction pathways and metabolic pathways in processes such as follicular development, oocyte maturation, ovulation, implantation, steroidogenesis, and maintenance of pregnancy. In the male reproductive system, ROS are critical in spermatozoa capacitation, hyperactivation, acrosome reaction and sperm-oocyte fusion [2, 3].
Nowadays, approximately 14 % of women in reproductive age have difficulties to conceive in the United States [1]. Several strategies have been utilized to overcome infertility, including assisted reproductive technology (ART). Although in vitro fertilization (IVF) is still the most commonly used technique, the number of ART cycles involving intracytoplasmic sperm injection (ICSI) has markedly increased [2].
Infertility affects approximately 15 % of couples worldwide [1]. During normal cellular metabolism, reactive oxygen species (ROS) are generated on a continuous basis, either by endogenous sources (see Chap. 1) or exogenous sources (see Chap. 5). ROS are essential for many processes in the human body, including essential intracellular signaling pathways [2]. Notwithstanding, an elevation in ROS eventually leads to oxidative stress (OS), defined as the imbalance between oxidants and antioxidants [3]. Oxidative stress can result in subfertility by negatively affecting multiple processes in the male and female reproductive systems.
Over the last two decades and more, the American Center for Reproductive Medicine (ACRM) at Cleveland Clinic has made great contributions to medicine that have helped in deepening our understanding of oxidative stress (OS) and its effects on human reproduction, particularly in the male. In this chapter, we will explore the findings of past research conducted by the Cleveland Clinic researchers to date, which spans from reactive oxygen species (ROS), OS and its measurement, effects of OS on sperm preparation and cryopreservation during assisted reproduction procedures as well as on semen parameters, the physiological and pathophysiological effects (both direct and indirect) of endogenous and exogenous ROS, the role of antioxidants in reversing the effects of oxidants and finally, the use of proteomics and bioinformatics tools in discovering the biological processes and pathways underlying oxidative stress-induced infertility.
... Hence, it is anticipated that this active constituent may cause the above events by changing the surface composition and could predict that inhibition may be responsible for plasma membrane damage, which may be the first result of the interaction of the active constituent with sperm, and then protease activity can be performed when this constituent enters the cytoplasm. Reports on sperm have shown that plasma membrane content is important for the movement of sperm to the fertilization site and that plasma membrane function is an important factor in sperm motility, sperm AR, capacitation, metabolism, and binding to ZP (Agarwal et al., 2017). Therefore, the results on sperm function indicate that nimbolide may affect the mitochondrial sheath component, which is important for early sperm motility or may have resulted in unbalanced metabolism. ...
... (Thompson et al., 2013). Studies have reported that ROS induces LPO and that the toxicity of lipid peroxides plays an important role in the inhibition of sperm function and the pathophysiology of male infertility (Agarwal et al., 2017). A proper level of H 2 O 2 plays an important role in sperm function including sperm maturation, chromatin stability, capacitation, hyperactivation of sperm, and acrosome reaction, and increases the rate of sperm-oocyte fusion (Aitken et al., 1995). ...
... A proper level of H 2 O 2 plays an important role in sperm function including sperm maturation, chromatin stability, capacitation, hyperactivation of sperm, and acrosome reaction, and increases the rate of sperm-oocyte fusion (Aitken et al., 1995). To counteract the effects of ROS, spermatozoa are equipped with antioxidant compounds such as GPx, SOD, GSH, and catalase resulting in disruption of membrane permeability, and thus efflux of ATP, impairing flagellar movement (Agarwal et al., 2017). Reports show that GSH-supplemented freezing extender improved sperm motility by reducing intracellular ROS levels, and improved sperm quality was associated with reduced LPO and increased antioxidant levels (Yánez-Ortiz et al., 2021). ...
... The biggest problem of spermatozoa storage is lipid oxidation in plasma membrane [1].The spermatozoa have a high concentration of fatty acids, the polyunsaturated fatty acid (PUFAs) in the spermatozoa plasma membrane are oversensitive to oxidation during semen storage [2]. The lipid peroxidation is responsible for decreased spermatozoa membrane permeability, ATP efflux and impairing sperm tail movement [3].The oxygen metabolism in cells is the of reactive oxygen species production (ROS) source, it is a byproduct and is a toxic metabolites which have a negative effect on the spermatozoa viability [3].There is a balance between ROS formation and removing by the endogenous antioxidants [2].The sperm are sensitive ROS as well as acidosis and loss of energy [5]. Increasing of ROS level maybe lead to sperm death specially during cooling storage [6].The Sperm cells have a natural defences line (endogenous antioxidants) to save the sperm cells against the oxidation [7].Endogenous antioxidants are chemicals can react with endogenous free radicals that form in the natural state [8].The ROS produce a free radicals, ROS with a low concentration consider a key for many biological roles [8].Increase of ROS may be cause the DNA, lipid, and proteins damage [10].Antioxidants improve sperm cell viability by keeping membrane integrity and sperm cell motility, the antioxidant activities assist in decreasing the negative effect of ROS [11].Adding vitamin B to the diluted bovine semen improves the sperm membrane against lipid peroxidation, where vitamin B is considered a source of antioxidants [12].The ATP store in the phosphagen system and depending on creatine kinase, and vitamin B acts as buffering and regenerates ATP [13]. ...
... The biggest problem of spermatozoa storage is lipid oxidation in plasma membrane [1].The spermatozoa have a high concentration of fatty acids, the polyunsaturated fatty acid (PUFAs) in the spermatozoa plasma membrane are oversensitive to oxidation during semen storage [2]. The lipid peroxidation is responsible for decreased spermatozoa membrane permeability, ATP efflux and impairing sperm tail movement [3].The oxygen metabolism in cells is the of reactive oxygen species production (ROS) source, it is a byproduct and is a toxic metabolites which have a negative effect on the spermatozoa viability [3].There is a balance between ROS formation and removing by the endogenous antioxidants [2].The sperm are sensitive ROS as well as acidosis and loss of energy [5]. Increasing of ROS level maybe lead to sperm death specially during cooling storage [6].The Sperm cells have a natural defences line (endogenous antioxidants) to save the sperm cells against the oxidation [7].Endogenous antioxidants are chemicals can react with endogenous free radicals that form in the natural state [8].The ROS produce a free radicals, ROS with a low concentration consider a key for many biological roles [8].Increase of ROS may be cause the DNA, lipid, and proteins damage [10].Antioxidants improve sperm cell viability by keeping membrane integrity and sperm cell motility, the antioxidant activities assist in decreasing the negative effect of ROS [11].Adding vitamin B to the diluted bovine semen improves the sperm membrane against lipid peroxidation, where vitamin B is considered a source of antioxidants [12].The ATP store in the phosphagen system and depending on creatine kinase, and vitamin B acts as buffering and regenerates ATP [13]. ...
This study was done in the Animal Field, Department of Animal Production Techniques, Technical Institute of Kufa, Al-Furat Al-Awsat Technical University, to evaluate the effect of adding vitamins (thiamine, pyridoxine, and cobalamin) to improve some goat semen diluent characteristics post-cooling. Five young male goats were used in this study, the experiment was divided into four groups, T1 (control), T2: thiamine (150 microgram (µg)/ 1 ml, T3: Pyridoxine 150 µg/1 ml and T4: Cobalamin (150 µg/1 ml). As the semen was collected and divided into four experimental treatments. The semen was stored for 24, 72 and 120 hours (hr.) at 5 ºC. The study recorded a highly significant rise in sperm motility percentage at 24 hr. by adding 150 µg thiamine, pyridoxine, and cobalamin compared with the T1 (control group) which noticed a high significant reduce during different times of cooling storage. The highest motility recorded after 120 hr. was noticed in group T2 (71.333±1.740) and T3 (70.499±2.027) followed by group T4 (67.833±2.185) than group T1 (control) (62.499±2.185). Non-significant effect of sperm abnormalities after 24 hr. between thiamine, pyridoxine, and cobalamin compared to the control group (T1), however, highly significant differences were shown after 72 hr. of cooling, the group T2 (thiamine) noticed highly significant abnormalities decrease at 72 hr. by 11.200+1.588 and non-significant variations were shown between T1, T3 (Pyridoxine) and T4 (Cobalamin). The results showed a significant decrease in the dead sperm percentage by adding thiamine, pyridoxine, and cobalamin to diluted goat semen after 24 and 72 hr. at cooling compared with the control group which were 18.833 ± 1.201 (T2), 22.167 ± 1.453 (T3), 22.000 ± 1.607 (T4) and 26.500 ± 1.527 (T1 control) for 24 hr. and 21.833 ± 1.443 (T2), 24.833 ± 1.166 (T3), 25.333 ± 2.309 (T4) and 29.500 ± 0.881 (T1 control) for 72 hr. respectively, while no significant differences observed among thiamine, pyridoxine, and cobalamin groups for first and second periods of cooling. After 24 hr., adding thiamine (T2) and cobalamin (T4) observed significantly increasing a high in host % by 76.333±1.453 and 76.167±1.453 respectively against the control group (72.000±0.763). Non-significant variations were noticed among thiamine (T2), and cobalamin (T4) for all periods of cooling. It could be concluded that adding the vitamins Thiamine, Pyridoxine, and Cobalamin at cooling periods have a positive role in enhancing the characteristics of cooled goat semen.
... The testes and spermatozoa mainly employ an antioxidant defense system composed of antioxidant enzymes such as catalase (CAT), glutathione peroxidase/glutathione reductase (GPX/GRD), superoxide dismutase (SOD), and also non-enzymatic antioxidants such as reduced glutathione (GSH), α-tocopherol, ascorbate, vitamin A, urate, pyruvate, albumin, taurine, and hypotaurine to prevent the harmful effects of ROS, [16,17]. ...
... Low levels of protective antioxidant enzymes as well as a higher concentration of PUFAs in membranes of cells cause spermatozoa more sensitive to oxidative stress [16,18]. Moreover, the lack of intracellular antioxidant enzymes around the tail and the acrosome to protect the plasma membrane makes spermatozoa wholly dependent on antioxidants of seminal plasma [19]. ...
Objectives
This in vivo study aimed to evaluate the effect of various concentrations of artemisinin (Art) alone or together with N-acetyl cysteine (NAC) on spermatological indices, antioxidant status, and histopathological parameters of testicular tissue in adult male mice.
Methods
Six groups of five healthy male mice (25–30 g) were randomly assigned to different experimental groups. These groups received DMSO and corn oil (0.1%) as an Art solvent (Control), 50 mg kg ⁻¹ Art (Art-50), 250 mg kg ⁻¹ Art (Art-250), 50 mg kg ⁻¹ Art + 150 mg kg ⁻¹ NAC (Art-50+NAC-150), 250 mg kg ⁻¹ Art + 150 mg kg ⁻¹ NAC (Art-250+NAC-150) and 150 mg kg ⁻¹ NAC (NAC-150) for a period of 7 days. Testes and epididymis were prepared to evaluate the malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), spermatological indices, and histological parameters.
Results
We showed that the high dose of Art (Art-250) significantly reduced the sperm count, motility, viability, and the activity of CAT and increased the levels of MDA compared to the control group. Also, the overdose of Art caused adverse changes in testicular tissue. Co-administration of NAC with Art (Art-250+NAC-150) corrected the adverse effects of Art.
Conclusions
The current study reports that a high dose of Art affects, spermatological parameters, antioxidant/stress oxidative status of the male reproductive system, and NAC is capable neutralize all adverse effects caused by Art.
... The major molecules i.e., the superoxide anion (O 2 •-), hydrogen peroxide (H 2 O 2 ) and the hydroxyl radical (HO • ), are called reactive oxygen species because they are oxygen-containing compounds with reactive properties. ROS may be radical or non-radical table 2.6 shows the two types of ROS, Unfastened radicals are molecules that contain as a minimum one unpaired valence electron at their outer shell, making them particularly reactive and brief-lived (Collin, 2019;Agarwal et al., 2017). Table 2.6. ...
... Table 2.6. radical and non-radical reactive oxygen species ROS (Agarwal et al., 2017) There are many essential roles for ROS in which formed during normal Singlet oxygen ( 1O 2 ) Ozone (O 3 ) Lipid peroxide (LOOH) ...
Osteoporosis is a situation that bones lose their power, density and quality also bone become more porous and fragile. The most effectible risk factors for osteoporosis are calcium and vitamin D deficiency, smoking, high amount alcohol intake, nutrients deficiency and insufficient exercise. In this study, blood serum samples were collected from patients with osteoporosis in the Department of Orthopedics and Traumatology, Faculty of Medicine, Van Yüzüncü Yıl University. The aim of this study was to determine the level of malondialdehyde (MDA), which is the end product of Lipid peroxidation by oxidative stress and some antioxidant activities such as reduced glutathione (GSH), catalase (CAT) and glutathione S-transferase (GST) were measured in the blood serum of osteoporosis patients. CAT, GSH and GST activities decreased significantly in patient groups compared to healthy control group (p <0.05), but MDA levels were significantly higher than healthy control group (p <0.05). In conclusion, any imbalance between antioxidants and oxidative stress may be the cause of the development of osteoporosis. Keywords: CAT, GSH, GST, MDA, Osteoporosis.
... The thiobarbituric acid (TBARS) assay is used to assess changes in Malonaldehyde (MDA), a reactive compound formed when lipids undergo oxidation (126). In conjunction with Thiobarbituric acid (TBA), MDA reacts to form the MDA-TBA adduct and can be measured colorimetrically or fluorometrically to determine the levels of lipid peroxidation in each sample (126). ...
... The thiobarbituric acid (TBARS) assay is used to assess changes in Malonaldehyde (MDA), a reactive compound formed when lipids undergo oxidation (126). In conjunction with Thiobarbituric acid (TBA), MDA reacts to form the MDA-TBA adduct and can be measured colorimetrically or fluorometrically to determine the levels of lipid peroxidation in each sample (126). The TBARS assay needs to be carried out under high temperatures and in an acidic environment. ...
Developing a deeper understanding of biological components of sperm is essential to improving cryopreservation techniques and reproductive technologies. To fully ascertain the functional determinants of fertility, lipidomic methods have come to the forefront. Lipidomics is the study of the lipid profile (lipidome) within a cell, tissue, or organism and provides a quantitative analysis of the lipid content in that sample. Sperm cells are composed of various lipids, each with their unique contribution to the overall function of the cell. Lipidomics has already been used to find new and exciting information regarding the fatty acid content of sperm cells from different species. While the applications of lipidomics are rapidly evolving, gaps in the knowledge base remain unresolved. Current limitations of lipidomics studies include the number of available samples to analyze and the total amount of cells within those samples needed to detect changes in the lipid profiles across different subjects. The information obtained through lipidomics research is essential to systems and cellular biology. This review provides a concise analysis of the most recent developments in lipidomic research. This scientific resource is important because these developments can be used to not only combat the reproductive challenges faced when using cryopreserved semen and artificial reproductive technologies in livestock such as cattle, but also other mammals, such as humans or endangered species.
... result, the selective permeability of the flagella is disrupted, causing the flow of Adenosine triphosphate (ATP) to be hindered, leading to impaired flagella movement [20]. Typically, the process of oxidation of membrane lipids results in a significant impairment in both the functionality and morphology of the membrane [21,22]. ...
In this study, which aimed to determine the preventive effect of Naringenin extracted from citrus aurantifolial on the damage caused by the methotrexate, in which 30 male rats were used, divided into five groups, which were control group dosed with Normal Saline (G1), second group dosed with methotrexate (G2) , third group dosed with Naringenin (15 to 15.5 mg) (G3), four group dosed with methotrexate and active Naringenin (G4) , fifth group dosed with methotrexate and Naringenin nanoparticles (G5) for two months, it was found that significantly increase the level of sex hormones and sperm parameters in G3 , G5 compared to G2 . It was also found that active Naringenin , Naringenin nanoparticles works to repair damage to the tissues of the testicles, epididymis and accessory glands caused by methotrexate the experimental group administered with G3,G4 and G5 had a typical testicular tissue shape characterized by tubules. Spermatozoa exhibit an elliptical morphology and are organized in a systematic and orderly fashion. the basement membrane envelops each tubule and contains sperm-generating cells, including dispersed Sertoli cells with triangle nuclei sperm progenitors In conclusion, the results of this article revealed It was found that Naringenin alone and Naringenin nanoparticles with the drug gave the best results on the methotrexate -induced male rats reproductive system
... Spermatozoa, like all other cell types, may defend themselves against oxidative damage. Although the existence and relevance of catalase in human spermatozoa are controversial, they are known to contain two alternative defensive mechanisms against the dioxygen species O2-and H2O2, namely SOD and the glutathione peroxidase/reductase pair (GPX/GRD) [13], [14]. Oxidative stress has been related to poor sperm quality and male infertility While low levels of reactive oxygen species (ROS) are required for male fertility [15]. ...
The significance of antioxidants and trace elements in the genesis and therapy of male infertility has garnered substantial interest. Male infertility is a common illness that affects couples worldwide. The purpose of this systematic review is to examine the available data on the effects of catalase (CAT), Glutathione (GSH), Glutathione peroxidase (GPX), Malondialdehyde (MDA), Calcium (Ca) and Magnesium (Mg) on male infertility. The study included the collection of 180 samples participating in the study and was distributed into three groups, the first group included men who have infertility with reason, and the second group included men who have infertility without reason, numbering (65 men). Comparison with a control group of (50 men), with ages ranging from 20 to 50 years. The levels of biochemical variables were estimated for them: CAT, GSH, GPX, MDA, Ca, and Mg. In addition, the study investigated the effect of age, smoking, BMI, and Period Infertility on these variables in male infertility patients. The study was conducted in the laboratories Scientific Center for Chemical Analysis (Baghdad-AL-Hartheyah-Kindy Street). The results were as follows: The result found significant differences (P ≤ 0.05) in tests of CAT and GSH at (5%) probability level of men infertile with reason and men infertile without reason compared with a control group. and showed the resultant found that GSH, GPX, and MDA have not revealed significant differences (P ≥ 0.05 n. s) among the infertile groups and the control group. Also, the show found decreased significant differences (P ≤ 0.01) in tests of Ca, and Mg at (1%) probability level of men infertile with reason and men infertile without reason compared with a control group. Also,
... ROS from both internal and external sources has an impact on biology ( Figure 5). Radiation, chemotherapeutic medications, pathogenesis, xenobiotics, etc. are some examples of external causes, while the internal elements are including cytokines, inflammation, mitochondria, and peroxisomes (99)(100)(101). ...
Cell cycle arrest (CCA) is seen as a prime candidate for effective cancer therapy. This mechanism can help researchers to create new treatments to target cancer cells at particular stages of the cell cycle (CC). The CCA is a characteristic of various therapeutic modalities, including radiation (RT) and chemotherapy (CT), which synchronizes the cells and facilitates the standardization of radio-chemotherapy protocols. Although it was discovered that photodynamic treatment (PDT) had a biological effect on CCA in cancer cells, the mechanism remains unclear. Furthermore, besides conventional forms of cell death such as apoptosis, autophagy, and necrosis, various unconventional types of cell death including pyroptosis, mitotic catastrophe, paraptosis, ferroptosis, necroptosis, and parthanatos after PDT have been reported. Thus, a variety of elements, such as oxygen, the tumor’s microenvironment, the characteristics of light, and photosensitizer (PS), influence the effectiveness of the PDT treatment, which have not yet been studied clearly. This review focuses on CCA induced by PDT for a variety of PSs agents on various cell lines. The CCA by PDT can be viewed as a remarkable effect and instructive for the management of the PDT protocol. Regarding the relationship between the quantity of reactive oxygen species (ROS) and its biological consequences, we have proposed two mathematical models in PDT. Finally, we have gathered recent in vitro and in vivo studies about CCA post-PDT at various stages and made suggestions about how it can standardize, potentiate, and customize the PDT methodology.
... It is reported that NO at low levels plays an important role in female reproductive physiology, while overproduction of NO was reported to induce GC apoptosis in several kinds of research (Budani & Tiboni 2021). Furthermore, because of the accelerated metabolism during follicular development, ROS accumulates rapidly in the follicles and can contribute to oxidative stress, which can induce GC apoptosis (Agarwal et al. 2017, Yang et al. 2017. Notably, ROS is primarily composed of H 2 O 2 , OH -, and O 2 -, and when the O 2 is produced in large quantity, it is easier to react with NO to form OONO - (Steller et al. 2018, Cui et al. 2023. ...
In brief
The apoptosis of granulosa cells (GCs) is the main reason for porcine follicular atresia. This study provides a novel mechanism for peroxynitrite anion-mediated GC apoptosis and follicular atresia in porcine ovary.
Abstract
Granulosa cells play a crucial role in the development of follicles, and their cell apoptosis in the porcine ovary is a major contributor to follicular atresia. Here, we provide a new mechanism for follicular atresia by describing a crucial mechanism by which peroxynitrite anion (OONO – ) may cause GC death. We discovered that nitric oxide, oxidative stress level, and OONO – were positively correlated with porcine follicular atresia, which was accompanied by high expression of matrix metalloproteinase 2 (MMP2) and MMP9. We created a model of OONO – -induced apoptosis in GCs and discovered that OONO – could boost the expression of MMP2 and MMP9 and increase the expression of pro-apoptotic proteins and DNA damage. Furthermore, by inhibiting the activities of MMP2 and MMP9, we found that SB-3CT (a specific inhibitor for MMP2 and MMP9) alleviated the decrease in cell survival rates and DNA damage caused by OONO – , which may have been impacted by reducing the cleavage of PARP1 by MMP2 and MMP9. Therefore, our findings imply that OONO – can cause DNA damage to GCs, participating in mediating the expression of pro-apoptotic proteins and inhibiting DNA repair by preventing the activity of PARP1 through MMP2 and MMP9. These results help explain how OONO – /MMP2/MMP9 affects porcine follicular atresia and GC apoptosis.
... radical (LOO • ), alkoxyl radical (LO • ), lipid hydroperoxide (LOOH), peroxynitrite (ONOO‾), hypochlorous acid (HOCl), and ozone (O 3 )[55]. Similarly, the term reactive nitrogen species (RNS) has been used to include nitric oxide ( • NO), peroxynitrite, nitrogen dioxide ( • NO 2 ), and other oxides of nitrogen or nitrogen-containing reactive species[56]. ...
... The activities of antioxidative enzymes in this study displayed similar trends or findings to those observed in former studies, suggesting that iron status may mediate testicular antioxidants and affect redox hemostasis. It has been reported that oxidative stress causes greater harmful effects in spermatozoa than in other cells [12,44], whereas both human and animal studies have demonstrated that SOD is present at relatively higher levels than other antioxidative enzymes, protecting spermatozoa via reduction of ROS [11,45,46]. The components of SOD contain metal ions [47], and our results showed that the iron-deficient rats had lower Mn-SOD and higher extracellular Cu/Zn-SOD protein expressions. ...
Iron deficiency is the most common micronutrient deficiency in the world. Previous studies have shown that iron deficiency increases oxidative stress and decreases antioxidant enzymes, and studies of male infertility indicated that oxidative stress may affect male reproductive functions. The aim of this study was to investigate the effects of iron supplementation on spermatogenesis and testicular functions in iron-deficient rats. Three-week-old male Sprague Dawley (SD) rats were randomly divided into two groups: an iron-adequate control (AI group, 35 ppm FeSO4) and an iron-deficient group (ID group, 12 ppm FeSO4 exhibited improvements in antioxidant levels. In conclusion, iron supplementation can abrogate testis dysfunction due to iron deficiency through regulation of the testicular antioxidant capacity.
... Due to inadequate cell repair systems, spermatozoa have very little cytoplasmic content and consequently, the insufficient antioxidant content is exposed to OS (Dutta et al., 2019). Spermatozoa contain high levels of polyunsaturated fatty acids (PUFAs) in their plasma membranes and are susceptible to membrane lipid peroxidation (LPO), which reduces membrane fluidity (Agarwal et al., 2017). As a result, the membrane structure of sperm is damaged, leading to reduced motility and fertilization (Cho et al., 2016). ...
Abstract Varicocele is considered the main reason for male infertility. Antioxidants are common drugs used to reduce the complications of varicocele in these patients. So, we investigated the effects of lycopene on sperm quality, testicular histology, and the expression of some genes in experimentally induced varicocele. Fifty adult male Wistar rats were divided into three groups: control (n = 12), sham (n = 5), and varicocele (n = 33) groups. After 2 months of induced varicocele, five rats were randomly sacrificed and induced varicocele was investigated in each group. Finally, 35 rats were divided into five groups: the control, varicocele, varicocele reserving solvent, and varicocele reserving lycopene (4 and 10 mg/kg) for 2 months. At the end of the experiment, sperm viability, membrane integrity, the expression of Bax, Bcl2, hypoxia (hypoxia‐inducible factor 1α [HIF1‐α]), heat‐shock protein (heat‐shock protein A2 [HSPA2]) genes, and the histology of testes were measured. The results showed a significant decrease in the sperm viability, membrane integrity, Johnson's score, and the expression of the Bcl2 gene in the varicocele group compared to the control group. Also, there was a significant increase in Bax, HSPA2, and HIF1‐α expressions in the varicocele group compared to the control group. Although the administration of lycopene (10 mg/kg) in rats with varicocele improved sperm viability and membrane integrity, Johnson's score, and Bax expression compared to the varicocele group. Our findings indicated that the administration of lycopene in the varicocele group improved sperm quality and testicular injury induced by varicocele via decreasing apoptosis.
... Lipid peroxidation is an oxidative degradation of lipids in the cell membranes which causes cellular damage (Sahu et al., 2020). The membrane damage can produce secondary metabolites such as malondialdehyde (MDA), which can impair the functionality of macromolecules like proteins, DNA, and lipids (Agarwal et al., 2017). The brain is particularly susceptible to oxidative stress (Quispe et al., 2019). ...
In continuation of our research to find strong and safe anticonvulsant agents, a number of (arylalkyl)azoles (AAAs) containing naphthylthiazole and naphthyloxazole scaffolds were designed and synthesized. The in vivo anticonvulsant evaluations in BALB/c mice revealed that some of them had significant anticonvulsant activity in both maximal electroshock (MES) and pentylenetetrazole (PTZ) models of epilepsy. The best profile of activity was observed with compounds containing imidazole and triazole rings (C1, C6, G1, and G6). In particular, imidazolylmethyl-thiazole C1 with median effective dose (ED50)= 7.9 mg/kg in the MES test, ED50= 27.9 mg/kg in PTZ test, and without any sign of neurotoxicity (in the rotarod test, 100 mg/kg) was the most promising compound. The patch-clamp recording was performed to study the mechanism of action of the representative compound C1 on hippocampal dentate gyrus (DG) cells. The results did not confirm any modulatory effect of C1 on the voltage-gated ion channels (VGICs) or GABAa agonism, but suggested a significant reduction of excitatory postsynaptic currents (EPSCs) frequency on hippocampal DG neurons. Sub-acute toxicity studies revealed that administration of the most active compounds (C1, C6, G1, and G6) at 100 mg/kg bw/day for two weeks did not result in any mortality or significant toxicity as evaluated by assessment of biochemical markers such as lipid peroxidation, intracellular glutathione, total antioxidant capacity, histopathological changes, and mitochondrial functions. Other pharmacological aspects of compounds including mechanistic and ADME properties were investigated computationally and/or experimentally. Molecular docking on the NMDA and AMPA targets suggested that the introduction of the heterocyclic ring in the middle of AAAs significantly affects the affinity of the compounds. The obtained results totally demonstrated that the prototype compound C1 can be considered as a new lead for the development of anticonvulsant agents.
... Oxidative stress by reactive oxygen species (ROS) is related to all the main changes observed in inflammatory and infectious diseases 118 . The spermatozoa are particularly susceptible to oxidative stress, leading to lipid peroxidation resulting in disruption of membrane permeability, and thus efflux of ATP, impairing flagellar movement 118,119 . The detrimental impact of oxidative stress on sperm parameters and fertility potential has been determined 120 . ...
Background:
Coronavirus disease 2019 (COVID-19), which causes serious respiratory illnesses such as pneumonia and lung failure, was first reported in mid-December 2019 in China and has spread around the world. In addition to causing serious respiratory illnesses such as pneumonia and lung failure, there have been conflicting reports about the presence of SARS-CoV-2 in the semen of patients who were previously diagnosed with COVID-19 and possible implications for the male reproductive tract.
Objective:
The goal for the present study was to review the current status of the literature concerning COVID-19 and male reproduction.
Material and methods:
An electronic literature search was done by using PubMed and Google Scholar databases. Relevant papers, concerning SARS-COV-2 and COVID-19 and male reproduction, published between January 2020 and December 2020 were selected, analyzed and eventually included in the present literature review.
Results:
SARS-CoV-2 may infect any cell type expressing angiotensin-converting enzyme 2 (ACE2), including reproductive cells. Besides the presence of the SARS-CoV-2 receptor, the expression of host proteases, such as transmembrane serine protease 2 (TMPRSS2), is needed to cleave the viral S protein, allowing permanent fusion of the viral and host cell membranes. Here, we aimed to review the current status of the literature concerning COVID-19 and male reproduction. The lack of co-expression of ACE2 and TMPRSS2 in the testis suggests that sperm cells may not be at increased risk of viral entry and spread. However, the presence of orchitis in COVID-19-confirmed patients and compromised sex-related hormonal balance among these patients intrigues reproductive medicine.
Discussion:
SARS-CoV-2 may use alternate receptors to enter certain cell types, or the expression of ACE2 and TMPRSS2 may not be detected in healthy individuals.
Conclusion:
COVID-19 challenges all medical areas, including reproductive medicine. It is not yet clear what effects, if any, the COVID-19 pandemic will have on male reproduction. Further research is needed to understand the long-term impact of SARS-CoV-2 on male reproductive function.
... At normal concentrations, they have vital roles in intracellular mechanisms and the regulation of vital signalling pathways including cell death, survival, differentiation, proliferation and inflammation-related factor production. However, high concentrations of ROS overcome the antioxidant defense system and create oxidative stress that disrupts the structure and function of lipids, proteins and nucleic acids [112,113]. ROSs are highly reactive and include oxygen anions (O À ), free radicals such as superoxide (O 2 À ), hydroxyl radicals (OH) and peroxides such as hydrogen peroxide (H 2 O 2 ). ROS production is the main effect of NPs toxicity in bacteria, which also affects their other antibacterial mechanisms ( Figure 5). ...
Bacterial infections are an important cause of mortality worldwide owing to the prevalence of drug resistant bacteria. Bacteria develop resistance against antimicrobial drugs by several mechanisms such as enzyme inactivation, reduced cell permeability, modifying target site or enzyme, enhanced efflux because of high expression of efflux pumps, biofilm formation or drug-resistance gene expression. New and alternative ways such as nanoparticle (NP) applications are being established to overcome the growing multidrug-resistance in bacteria. NPs have unique antimicrobial characteristics that make them appropriate for medical application to overcome antibiotic resistance. The proposed antibacterial mechanisms of NPs are cell membrane damage, changing cell wall penetration, reactive oxygen species (ROS) production, effect on DNA and proteins, and impact on biofilm formation. The present review mainly focuses on discussing various mechanisms of bacterial drug resistance and the applications of NPs as alternative antibacterial systems. Combination therapy of NPs and antibiotics as a novel approach in medicine towards antimicrobial resistance is also discussed.
... The spermatozoa are particularly susceptible to OS owing to their inadequate cell repair systems, as well as insufficient antioxidant defences due to very little cytoplasmic content. They are susceptible to lipid peroxidation (LPO) due to the high content of polyunsaturated fatty acids (PUFAs) in their plasma membrane, resulting in disruption of membrane permeability, and thus efflux of ATP, impairing flagellar movement [5,6]. A number of studies have confirmed the detrimental impact of OS on semen parameters and fertility potential. ...
... The spermatozoa are particularly susceptible to OS owing to their inadequate cell repair systems, as well as insufficient antioxidant defences due to very little cytoplasmic content. They are susceptible to lipid peroxidation (LPO) due to the high content of polyunsaturated fatty acids (PUFAs) in their plasma membrane, resulting in disruption of membrane permeability, and thus efflux of ATP, impairing flagellar movement [5,6]. A number of studies have confirmed the detrimental impact of OS on semen parameters and fertility potential. ...
Objective: To review and present the most distinct concepts on the association of reactive oxygen species (ROS) with male reproduction.
Methods: The Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines were used to search PubMed, Medline, EMBASE, and the Cochrane electronic databases for studies investigating the role of oxidative stress (OS) on sperm function.
Results: The literature search yielded 1857 studies, of which 1791 articles were excluded because of irrelevance of data, non-English language, non-human nature or because they were case reports or commentaries. All included studies were reviews (46), meta-analyses (one), original research studies (18) and guideline articles (one). The studies were published between 1984 and 2018. Under normal physiological conditions, ROS are vital for sperm maturation, hyperactivation, capacitation, acrosome reaction, as well as fertilisation. However, a number of endogenous and exogenous causes may induce supra-physiological levels of ROS resulting in lipid peroxidation, sperm DNA fragmentation and apoptosis, and consequently infertility. Several laboratory testing methods can be used in infertile men to diagnose OS. Treatment usually involves antioxidant supplementation and, when possible, elimination of the causative factor.
Conclusion: OS is an important cause of male factor infertility. Its assessment provides essential information that can guide treatment strategies aimed at improving the male’s reproductive potential.
Abbreviations: bp: base-pair; CAT: catalase; LPO: lipid peroxidation; MDA: malondialdehyde; MiOXSYS: Male Infertility Oxidative System; mtDNA: mitochondrial DNA; NAD(PH): nicotinamide adenine dinucleotide (phosphate); NO: nitric oxide; 8-OHdG: 8-hydroxy-2’-deoxyguanosine; ORP: oxidation–reduction potential; OS: oxidative stress; PKA: protein kinase A; PLA2: phospholipase A2; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PUFA: poly-unsaturated fatty acid; ROS: reactive oxygen species; SOD: superoxide dismutase; TAC: total antioxidant capacity; TBA: thiobarbituric acid
... This value was adjusted for sperm concentration and ROS were reported as RLU/s/10 6 sperm [29], and specimens were classified according to seminal ROS levels into four groups: group 1 (n = 39): low (ROS < 20 RLU/s/10 6 sperm), group 2 (n = 38): mild (20 RLU/s/10 6 sperm ≤ ROS < 40 RLU/s/10 6 sperm), group 3 (n = 31): moderate (40 RLU/s/10 6 sperm ≤ ROS < 60 RLU/s/ 10 6 sperm), and group 4 (n = 43): high (ROS ≥ 60 RLU/s/10 6 sperm). These four groups were determined based on the previous studies which showed that high ROS level could damage sperm chromatin and decrease ART outcomes [30][31][32]. For quality control of the assay, intra-assay coefficient of variation (CV) was calculated in three levels of ROS concentrations in 15 replications and all the resultant CVs were less than 10%. ...
Purpose
This study was conducted in order to investigate the effects of reactive oxygen species (ROS) levels on the seminal plasma (SP) metabolite milieu and sperm dysfunction.
Methods
Semen specimens of 151 normozoospermic men were analyzed for ROS by chemiluminescence and classified according to seminal ROS levels [in relative light units (RLU)/s/106 sperm]: group 1 (n = 39): low (ROS < 20), group 2 (n = 38): mild (20 ≤ ROS < 40), group 3 (n = 31): moderate (40 ≤ ROS < 60), and group 4 (n = 43): high (ROS ≥ 60). A comprehensive analysis of SP and semen parameters, including conventional semen characteristics, measurement of total antioxidant capacity (TAC), sperm DNA fragmentation index (DFI), chromatin maturation index (CMI), H19-Igf2 methylation status, and untargeted seminal metabolic profiling using nuclear magnetic resonance spectroscopy (1H-NMR), was carried out.
Result(s)
The methylation status of H19 and Igf2 was significantly different in specimens with high ROS (P < 0.005). Metabolic fingerprinting of these SP samples showed upregulation of trimethylamine N-oxide (P < 0.001) and downregulations of tryptophan (P < 0.05) and tyrosine/tyrosol (P < 0.01). High ROS significantly reduced total sperm motility (P < 0.05), sperm concentration (P < 0.001), and seminal TAC (P < 0.001) but increased CMI and DFI (P < 0.005). ROS levels have a positive correlation with Igf2 methylation (r = 0.19, P < 0.05), DFI (r = 0.40, P < 0.001), CMI (r = 0.39, P < 0.001), and trimethylamine N-oxide (r = 0.45, P < 0.05) and a negative correlation with H19 methylation (r = − 0.20, P < 0.05), tryptophan (r = − 0.45, P < 0.05), sperm motility (r = − 0.20, P < 0.05), sperm viability (r = − 0.23, P < 0.01), and sperm concentration (r = − 0.30, P < 0.001).
Conclusion(s)
Results showed significant correlation between ROS levels and H19-Igf2 gene methylation as well as semen parameters. These findings are critical to identify idiopathic male infertility and its management through assisted reproduction technology (ART).
Exploring the synergistic effect of docosahexaenoic acid (DHA) or conjugated linoleic acid (CLA) with caffeic acid (CA) on ameliorating oxidative stress, thereby introducing CA to DHA or CLA will contribute significantly to enhance the bioactivity. We observed that DHA or CLA with CA promoted the recovery of intact individual morphology and the decline of cavities inside the nucleus and apoptosis under the observation of confocal laser scanning microscopy and fluorescent inverted microscope. The activity of intracellular antioxidant enzymes catalase (CAT) and glutathione peroxidase (GSH‐Px), lactate dehydrogenase (LDH) leakage, pyruvate and malondialdehyde and reactive oxygen species (ROS), cellular morphology, and cell cycle were analyzed. Our results showed that DHA or CLA with CA enhanced the activity of CAT and GSH‐Px, decreased LDH leakage and the number of apoptotic, significantly inhibited (ROS‐induced cellular injury. Cell arrest in G1 and G2 phase during cell mitosis was reduced by the measurement of flow cytometry. DHA or CLA combined with CA could markedly strengthen the free radical scavenging and endogenous antioxidant defense capacity on HepG2 cells. This study provides a new direction in the application of synergies to antioxidant compounds.
Practical Application
Caffeic acid (CA) can synergize with docosahexaenoic acid (DHA) or conjugated linoleic acid (CLA) to enhance antioxidant capacity. This study highlighted an effect of ameliorating oxidative stress injury DHA or CLA with CA on HepG2 cells. The data indicated that DHA or CLA with CA might be used to relieve oxidative stress damage.
Reducing oxidative species to non- or less-reactive matter is the principal function of an antioxidant. Plant-based food is the main external source of antioxidants that helps protect our cells from oxidative damage. During postharvest storage and distribution, fruits and vegetables often increase ROS production that is quenched by depleting their antioxidant pools to protect their cells, which may leave none for humans. ROS are molecules produced from oxygen metabolism; some of the most widely analyzed ROS in plants are singlet oxygen, superoxide, hydrogen peroxide, and hydroxyl radicals. ROS concentration and lifetime are determined by the availability and composition of the antioxidant system that includes enzymatic components such as SOD, CAT, and APX and nonenzymatic components such as vitamins, polyphenols, and carotenoid. Depending on its concentration in the cell, ROS can either be harmful or beneficial. At high concentrations, ROS can damage various kinds of biomolecules such as lipids, proteins, DNA, and RNA, whereas at low or moderate concentrations, ROS can act as second messengers in the intracellular signaling cascade that mediates various plant responses. Novel postharvest methods are sought to maintain fruit and vegetable quality, including minimizing ROS while preserving their antioxidant content.
The review article provides an overview of the contemporary research based on a tailor-made technique for polymers of different classes. The ubiquity of free radicals, including biradicals, triplet states, and point defects in polymer systems has rendered EPR spectroscopy an indispensible tool in polymer science among other mainstream analytical techniques. The scope of EPR spectroscopy has broadened particularly due to the growing impulse to produce polymers with enhanced stability, to follow the charge transfer process in conducting polymers, to decipher the complex nanoscale dynamics of polymers, to fathom out reaction mechanisms and kinetics of complex polymer reactions in a more facile way, and to carry out comprehensive structural and conformational analyses. Recent studies have hinted at the effectiveness of EPR spectroscopy in collecting data with sub-nanometer spatial resolution to decipher intrinsic intricacies, while keeping the pristine geometry unperturbed, a task yet not achievable with other conventional techniques. EPR spectroscopy is being applied to polymer science in multifarious ways, including, but not limited to, exploring structure, conformation, and dynamics of polymer chain segments, degradation or defect studies, charge transfer properties, kinetics and reaction mechanisms especially of free radical polymerization reactions, and EPR imaging of polymer matrix. A surge in its recent applications indicates that EPR spectroscopy is going to have a profound influence in polymer science in upcoming years.
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