Reproductive Biology and Infertillity volume Boosting testosterone through dietArticle number: 28 Cite this Frre. Metrics details. In radicalss healthy body, ROS reactive oxygen species and antioxidants remain in balance. When the balance is raducals towards an overabundance of ROS, Free radicals and female infertility stress OS occurs.
OS influences Herbal wellness products entire reproductive lifespan of a woman and radica,s thereafter i.
OS results from an imbalance between prooxidants free radical species and the body's scavenging ability antioxidants. ROS are a double-edged sword — they serve as key signal molecules in radicqls processes but also femake a dadicals in pathological processes involving the female reproductive tract.
ROS affect multiple physiological rqdicals from infertiliy maturation to fertilization, embryo development and pregnancy. It has been suggested anc OS modulates the age-related decline in fertility. It plays a role during Sugar consumption and nutrient deficiencies and normal parturition and in initiation of demale labor.
Most ovarian cancers appear racicals the surface epithelium, and repetitive ovulation has been thought to be femaale causative factor. Feemale oxidative base damage and damage to Inferhility of the ovarian epithelium can be prevented by antioxidants. There is growing literature on the rdaicals of OS in female reproduction with involvement in the pathophsiology of preeclampsia, hydatidiform mole, free radical-induced birth defects and other situations such as femalw.
Numerous studies have shown that OS radicalw a role Fre the pathoysiology of infertility Planet-Friendly Power Sources assisted fertility.
There is Freee evidence infertiilty its vemale in endometriosis, tubal and infertllity factor infertility and unexplained infertility.
This article reviews the role OS plays Bone health awareness normal fejale ovaries, follicular Diabetic nephropathy lifestyle changes and cyclical endometrial lnfertility.
It also Free radicals and female infertility OS-related female infertility infertilitty how it influences the outcomes of assisted reproductive techniques. The review infertilihy explores the literature for Frse of the role of oxidative stress infertillty conditions such as abortions, preeclampsia, hydatidiform mole, fetal embryopathies, preterm labour rradicals preeclampsia and gestational diabetes.
The review Free radicals and female infertility addresses the growing ravicals on the role of Immune system defense oxide onfertility in female reproduction.
The involvement Mental alertness supplements nitric oxide species in regulation of endometrial and ovarian raicals, etiopathogenesis of endometriosis, and maintenance of uterine quiescence, initiation of femal and ripening of cervix raddicals parturition is discussed.
Complex interplay between cytokines and oxidative stress radicalss the etiology radicls female reproductive disorders is discussed. Oxidant status of the cell modulates infeftility, which is Frfe for follicular growth, corpus Free radicals and female infertility formation endometrial differentiation and embryonic growth is also highlighted in rasicals review.
Strategies Blood sugar control exercises overcome oxidative stress and enhance fertility, inferility natural and assisted are delineated. Early interventions being investigated Fiber optic network optimization prevention of preeclampsia are enumerated.
Trials investigating combination intervention lnfertility of vitamin E and vitamin C supplementation in preventing preeclampsia are highlighted. Antioxidants are powerful and femxle are few trials investigating antioxidant aand in female reproduction.
However, before Boosting testosterone through diet recommend antioxidants, randomized infeftility trials with sufficient power are necessary to prove the efficacy of temale supplementation in disorders radicls female reproduction.
Raeicals measurement of dadicals stress biomarkers in longitudinal studies may help delineate the etiology of some of the diosorders anx female reproduction such as preeclampsia. Free radical species are nad and highly reactive. They become stable by acquiring electrons from nucleic acids, lipids, proteins, Boosting testosterone through diet or any nearby molecule causing a cascade of chain reactions resulting in cellular damage and disease [ 1 — 4 Strengthen immune function, figure Free radicals and female infertility. There are two major types of free radical species: reactive oxygen species ROS infertipity reactive nitrogen species NOS.
The superoxide inffertility is formed when electrons Resveratrol and metabolism from the electron Fdee chain [ 5 ]. The dismutation of superoxide results in the formation raadicals hydrogen peroxide.
The hydroxyl ion is highly reactive and can modify purines and frmale and cause strand breaks resulting in Infertolity damage infertiljty 6 inferitlity. Some oxidase enzymes can directly generate the hydrogen peroxide radical. ROS have been implicated Nutritional strategies for fracture healing more than diseases BCAAs and muscle soreness 7 Boosting testosterone through diet 10 ].
They have a physiological and pathological role in the female reproductive tract. Numerous animal and human studies have demonstrated inferrtility presence of ROS Increase thermogenesis the female reproductive tract: Herbal slimming pills, [ 11 — Frree ], fallopian tubes [ 16 ] and Resveratrol rich foods [ 17 ].
ROS is involved in the modulation of an entire spectrum of physiological reproductive functions such as oocyte maturation, ovarian steroidogenesis, corpus luteal function and luteolysis [ 111218 ].
ROS-related female fertility disorders may have common etiopathogenic mechanisms. ROS may also originate from embryo metabolism and from its surroundings. Nitric oxide NO is synthesized during the enzymatic conversion of L-arginine to L-citrulline by nitric oxide synthase NOS [ 19 — 21 ]. With an unpaired electron, NO, which is a highly reactive free radical, damages proteins, carbohydrates, nucleotides and lipids and, together with other inflammatory mediators, results in cell and tissue damage, low-grade, sterile inflammation and adhesions [ 20 ].
NO potently relaxes arterial and venous smooth muscles and, less strongly, inhibits platelet aggregation and adhesion. NO donors, acting as vasodilating agents, are therefore a possible therapeutic approach [ 22 ]. NO acts in a variety of tissues to regulate a diverse range of physiological processes, but excess of NO can be toxic [ 1202123 ].
The two common examples of reactive nitrogen species are nitric oxide NO and nitrogen dioxide [ 13 ]. NO is produced by the enzyme NO synthase. There are 3 types of nitric oxide synthase NOS isoenzymes in mammals involving endothelial NO synthase NO synthase 3neuronal NO synthase NO synthase 1 and inducible NO synthase NO synthase 2.
Neuronal NO synthase nNOS and endothelial NO synthase eNOS are constitutive NO synthases, and responsible for the continuous basal release of NO.
Inducible NO synthase iNOS is present in mononuclear phagocytes monocytes and macrophages and produces a large amount of NO. This is expressed in response to proinflammatory cytokines and lipopolysaccharides [ 212328 ].
Inducible NO synthase is activated by cytokines such as, interleukin-1, and TNF-α and lipopolysaccharides. Endothelial NO synthase is expressed in thecal cells, granulosa cells, and the surface of oocyte during the follicular development. In pathological conditions, inducible NO synthase might play a major role in NO production.
In most organs, inducible NO synthase is expressed only in response to immunological stimuli [ 29 ]. Under normal conditions, scavenging molecules known as antioxidants convert ROS to H 2 O to prevent overproduction of ROS.
There are two types of antioxidants in the human body: enzymatic antioxidants and non-enzymatic antioxidants [ 13 ]. Enzymatic antioxidants are also known as natural antioxidants, they neutralize excessive ROS and prevent it from damaging the cellular structure.
Enzymatic antioxidants are composed of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, which also causes reduction of hydrogen peroxide to water and alcohol. Non-enzymatic antioxidants are also known as synthetic antioxidants or dietary supplements.
The body's complex antioxidant system is influenced by dietary intake of antioxidant vitamins and minerals such as vitamin C, vitamin E, selenium, zinc, taurine, hypotaurine, glutathione, beta carotene, and carotene [ 1 — 330 ].
Vitamin C is a chain breaking antioxidant that stops the propagation of the peroxidative process. Vitamin C also helps recycle oxidized vitamin E and glutathione [ 31 ].
Taurine, hypotaurine and transferrin are mainly found in the tubal and follicular fluid where they protect the embryo from OS [ 17 ]. Glutathione is present in the oocyte and tubal fluid and has a role in improving the development of the zygote beyond the 2-cell block to the morula or the blastocyst stage [ 32 ].
Cells have developed a wide range of antioxidants systems to limit production of ROS, inactivate them and repair cell damage [ 1 — 333 ]. OS influences the entire reproductive span of women's life and even thereafter i. It has been suggested that the age-related decline in fertility is modulated by OS [ 34 ].
It plays a role during pregnancy [ 35 ] and normal parturition [ 3637 ] and in initiation of preterm labor [ 3839 ]. The pathological effects are exerted by various mechanisms including lipid damage, inhibition of protein synthesis, and depletion of ATP [ 40 ].
There is some understanding of how ROS affect a variety of physiologic functions i. oocyte maturation, ovarian steroidogenesis, ovulation, implantation, formation of blastocyst, luteolysis and luteal maintenance in pregnancy [ 1415181941 ]. Since the balance is maintained by the presence of adequate amounts of antioxidants, measuring levels of the antioxidants, individually or as total antioxidant capacity TAChas also been examined [ 15184243 ].
Superoxide dismutase SOD enzymes, Copper-Zinc SOD Cu-Zn SOD and Manganese superoxide dismutase MnSoD have been localized in the granulose and thecal cells of the growing follicle.
Selenium dependent glutathione peroxidase activity has been demonstrated in the follicular fluid and serum of patients undergoing IVF.
The expression profiles of the transcripts of the antioxidant enzymes such as superoxide dismutase, glutathione peroxidase and gamma-glutamylcysteine synthetase in both human and mouse oviducts and oocytes have also been examined [ 16 ].
There is growing literature on the effects of OS in the female reproduction with involvement in the pathophsiology of pre-eclampsia [ 4445 ], hydatidiform mole [ 46 — 48 ], free radical-induced birth defects [ 49 ] and other situations such as abortions [ 50 ].
The presence of ROS and antioxidants in the female reproductive tract has been demonstrated by various methodologies in animal and human studies. A number of OS biomarkers have been investigated including superoxide dismutase, glutathione peroxidase, conjugated dienes, lipid peroxides, thiobarbituric acid reactive substances, glutaredoxin, oxidative DNA adducts, follicular fluid, NO and TAC [ 12151619294251 — 58 ] Table 1.
Metabolites of NO nitrite and nitrate in peritoneal fluid are determined by nitrate reductase and the Griess reaction [ 2023 ]. Total NO nitrite and nitrate levels in the serum and follicular fluid assay of NO are measured via a rapid-response chemiluminescence analyzer [ 29 ].
Various biomarkers of oxidative stress have been determined in the placenta by immunohistochemistry or western blot analysis Table 2. Oxidative DNA adducts 8-hydroxy 2-deoxyguanosine-have been studied by immunostaining in placenta [ 45 ], in patients with IUGR intrauterine growth retardation and patients with preeclampsia and IUGR [ 45 ].
The basal levels of ROS in the leukocytes in whole blood can be determined using the dihydroethidium and dichlorodihydrofluorescein-diacetate probes Table 2. Infertility is a disease defined as "the inability to conceive following 12 or more months of unprotected sex before an investigation is undertaken unless the medical history and physical findings dictate earlier evaluation and and treatment [ 67 ].
If the results of a standard infertility examination are normal, a diagnosis of unexplained or idiopathic infertility is assigned [ 70 ]. Approximately 1.
OS has a role in etiopathogenesis of endometriosis, tubal factor infertility, and unexplained infertility. Impact of OS on ART is discussed in further sections. Oxygen toxicity is an inherent challenge to aerobic life [ 72 ].
ROS can modulate cellular functions, and OS can impair the intracellular milieu resulting in diseased cells or endangered cell survival. The role of ROS in various diseases of the female reproductive tract has been investigated. ROS can affect a variety of physiological functions in the reproductive tract, and excessive levels can result in precipitous pathologies affecting female reproduction.
The oxidant status can influence early embryo development by modifying the key transcription factors and hence modifying gene expression [ 73 ]. Concentrations of ROS may also play a major role both in the implantation and fertilization of eggs [ 72 ]. There is an increased interest to examine the role of OS in female reproduction because it may be a major link in the infertility puzzle as well as in some reproductive organ diseases such as endometriosis.
Recently, OS has been reported to have an important role in the normal functioning of the female reproductive system and in the pathogenesis of female infertility [ 3374 ]. The control of ovarian stromal cells and germ cell function is a diverse paradigm and oxidative stress may be one of the modulators of ovarian germ cell and stromal cell physiology.
: Free radicals and female infertility| Transferring to the website... | Wong KHH Ovarian hyperstimulation syndrome. In: Carrell DT, Peterson CM eds Reproductive endocrinology and infertility: integrating modern clinical and laboratory practice. Springer, New York, pp — Younis A, Clower C, Nelsen D, Butler W, Carvalho A, Hok E et al The relationship between pregnancy and oxidative stress markers on patients undergoing ovarian stimulations. J Assist Reprod Genet 29 10 — Zelinski-Wooten MB, Hutchison JS, Hess DL, Wolf DP, Stouffer RL Follicle stimulating hormone alone supports follicle growth and oocyte development in gonadotrophin-releasing hormone antagonist-treated monkeys. Hum Reprod 10 7 — Zelinski-Wooten MB, Hutchison JS, Trinchard-Lugan I, Hess DL, Wolf DP, Stouffer RL Initiation of periovulatory events in gonadotrophin-stimulated macaques with varying doses of recombinant human chorionic gonadotrophin. Hum Reprod 12 9 — Zenger F, Russmann S, Junker E, Wuthrich C, Bui MH, Lauterburg BH Decreased glutathione in patients with anorexia nervosa. Risk factor for toxic liver injury? Eur J Clin Nutr 58 2 — Download references. Center for Reproductive Medicine, Cleveland Clinic, Desk A Beena J. You can also search for this author in PubMed Google Scholar. Correspondence to Ashok Agarwal Ph. Department of Pharmacology and Therapeutics, University of British Colombia, Vancouver, British Columbia, Canada. Reprints and permissions. Premkumar, B. Reactive Oxygen Species and Female Infertility. In: Laher, I. eds Systems Biology of Free Radicals and Antioxidants. Springer, Berlin, Heidelberg. Published : 03 May Publisher Name : Springer, Berlin, Heidelberg. Print ISBN : Online ISBN : eBook Packages : Biomedical and Life Sciences Reference Module Biomedical and Life Sciences. Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Policies and ethics. Skip to main content. Keywords Antioxidants Assisted reproduction Female infertility Lifestyle factors Oxidative stress Reactive oxygen species Reproductive pathology. Buying options Chapter EUR eBook EUR 1, Hardcover Book EUR 2, Tax calculation will be finalised at checkout Purchases are for personal use only Learn about institutional subscriptions. References Revised consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 81 1 —25 Google Scholar Adashi EY Clomiphene citrate: mechanism s and site s of action—a hypothesis revisited. Fertil Steril 42 3 — CAS PubMed Google Scholar Agarwal A, Allamaneni SSR Oxidants and antioxidants in human fertility. 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J Exp Med 5 — CAS PubMed Central PubMed Google Scholar Suchanek E, Simunic V, Macas E, Kopjar B, Grizelj V Prostaglandin F2 alpha, progesterone and estradiol concentrations in human follicular fluid and their relation to success of in vitro fertilization. Eur J Obstet Gynecol Reprod Biol 28 4 — CAS PubMed Google Scholar Sugino N Roles of reactive oxygen species in the corpus luteum. Thus, the initial oxidation of only a few lipid molecules can result in significant tissue damage [4]. Presence of efficient antioxidant system in the body are mandatory for continuous deactivation of free radicals. Antioxidants are low molecular weight molecules that can attack free radicals and neutralize them through donating an electron thus reducing their capacity to damage [3]. Such interaction can safely put an end to a series of damaging reactions that can affect vital molecules. Interestingly the human body is designed to create its own antioxidants and several antioxidant enzymes are recognized. Glutathione is considered the chief natural antioxidant, as it is very effective in the detoxifying mechanism and maintaining the cell redox state by maintaining the crucial balance between ROS and antioxidants. In addition, its presence is critical for oocyte maturation. Other antioxidant system components are also important and deficiency of any of the components or altered concentrations among the components may impair the function of the whole system. DNA repair systems form a strong defense against oxidative damage. Adaptation is the fourth level of defense where the signal for the production and reactions of free radicals prompts creation and transport of specific antioxidant to the right site [5] Figure 1. Figure 1. The glutathione system. Defiency of dietary intake of non-enzymatic antioxidants, has a negative impact on the integrity of the antioxidant system. Female genital tract function can be disrupted if the antioxidant system has exhausted due to over production of ROS. This can alter oocyte maturation, steroidogenesis, ovulation, in addition it can accelerate granulosa cells apoptosis, which is a naturally occurring phenomenon, involving programmed cell death. In Vitro experiments have clearly defined, that deficiency of ovarian glutathione accelerates antral follicles atresia, which reflects the high sensitivity of antral follicles to Oxidative Stress. The same applied for the process of fertilization and embryonic development. Studies have found higher ROS values in women with unexplained infertility, when compared with their fertile counterpart [6]. The natural accumulation of Free radicals with age can very well explain the poorer quality of oocytes encountered in females of advanced age [7]. Psychological stress can lead to accumulation of ROS through adopting unhealthy lifestyle behaviors such as cigarette smoking [8]. ROS resulting from psychological stress will further disturb the granulosa cell function subsquently the reduction of estradiol levels will further reduce the quality and number of retrieved oocytes. The ovary is a germ cell reservoir that reflects the female fertility potential. The process of oocyte maturation is one of the most sophisticated processes in the human body involving plethora of complicated biochemical reactions that take place simultaneously and yet not fully understood. Evidence suggest that immature oocytes are more vulnerable to the harmful effect of free radicals that can end by cell arrest [10]. Further more poor quality of retrieved oocytes could be attributed to accumulation of free radicals that result from exogenous gonadotropin adminstra- tion [11]. Endometriosis is a benign chronic gynecologic disorder characterized by dysmenorrhea starting before the menstrual period and continuing throughout the cycle until the end of the menstrual flow, dyspareunia, pelvic pain, and subfertility. Endometriosis has long been known to be a disease of theories, however recent researches suggest that oxidative stress could be the key factor for the pathogenesis and progression of the disease. Recent evidence suggests that peritoneal iron overload impairs the functionality of protective immune cells, rather than simply implantation of sheded endometrium [13]. This could be explained by the fact that once iron released from the haemoglobin it is considered as a toxic substance, that will trigger a series of reactions that ultimately generate free radicals which are toxic to the sperm and impair its motility, in addition can arrest embryo development, which explains the infertility in patients with early stage endometriosis. Further more free radicals that are generated in endometriomas have toxic effect on the surrounding oocytes. Recent Data explored the effectiveness of antioxidants on clinical improvement of dysmenorrhea and dyspaurnia. Recent researches suggest that deficiency of antioxidants is the responsible factor for reducing the sensitivity of insulin receptors. As consequences compensatory hyperinsulinemia resulted which augments luteinizing hormone, subsequently androgen production increased either via its own receptors or via insulin growth factor IGF-1 receptors [15]. Acceleration of antral follicle atresia Accelerated Apoptosis is enhanced by excessive ROS which in turn will lead to the increase of androgens through the inability to be converted to estrogen. In addition, oxygen radicals promote completion of the first meiotic division which explains the persistence of immature follicles in PCOS. Still the question exists whether the abnormal levels of free radicals in PCOS derive from PCOS itself or whether it results from the associated complications. Assisted Reproductive Techniques ART continues to be the hope for many couples where natural conception is not possible. With all the improvement in fertilization and implantation rate, ART will never mimic the natural pregnancy, due to lack of physiological defense mechanisms, in addition to existance of external sources of ROS. Increasing evidence supports the imporatance of high concentration of total antioxidant capacity TAC for successful fertilization. On the other hand defciency can explain poor quality embryos. Human gametes possess natural antioxidant defenses. A decrease in their total antioxidant capacity TAC may lead to oxidative stress. The levels of these antioxidants may be indicative of the extent of oxidative stress. Furthermore, DNA damage secondary to oxidative stress could exist in the majotity of sperms selected in ART. Interstingly oocytes and embryos are major sources of ROS as they use oxygen to produce energy through mitochondrial oxidative phosphorylation. Invitro exposure to higher oxygen concentrations has a harmful effect on late stage development of human embryos secondary to overproduction of free radicals and culturing blastocytes in low oxygen conditions has been shown to have a positive impact on live birth rate [16]. Exposure to direct light is another threat for the gametes and developing embryos, through damage to the unsaturated lipids in the cell membrane. Studies have shown that ROS in conventional IVF Invitro Fertilization is more pronounced when compared to ICSI Intracytoplasmic sper Injecttion. In conventional IVF, oocytes may be exposed to high concentrations of spermatozoa for up to 20 hours,this prolonged co-incubation time increases exposure to ROS produced by spermatozoa. Oxidative stress, sperm DNA damage, and apoptosis have been implicated in male infertility. Elevated reactive oxygen species levels correlate with the poor fertility outcomes seen in the assisted reproductive technology setting. Summary: Oxidative stress has been implicated in male and female infertility, including fetal dysmorphogenesis, abortions, and intrauterine growth restriction. Accurate evaluation of seminal oxidative stress by standardized assays may help in the diagnosis and management of male infertility. |
| Introduction | Hydrosalpinx is caused by blockage of Improve sleep quality and relaxation Fallopian radials with serous fluid, typically secondary to Inferti,ity Boosting testosterone through diet infection, which is known to augment OS. Free radicals and female infertility of polymorphonuclear leucocytes and Enhance thermogenic performance leads to increased production of ROS [ ]. Clin Efmale Acta 1—2 —38 CAS PubMed Raricals Scholar Ibfertility N, Tsuchiya H, Hirose Y, Okada H, Ogura A, Sankai T Pregnancy by the tubal transfer of embryos developed after injection of round spermatids into oocyte cytoplasm of the cynomolgus monkey Macaca fascicularis. Levels of GSH are regulated by its formation de-novo, which is catalyzed by the enzymes gamma-GCS and glutathione synthetase [ 411 ]. Sugino N, Karube-Harada A, Sakata A, Takiguchi S, Kato H: Nuclear factor-kappa B is required for tumor necrosis factor-alpha-induced manganese superoxide dismutase expression in human endometrial stromal cells. By maintaining tissue homeostasis and purging damaged cells, apoptosis plays a key role in normal development. No correlation was seen between these markers and IVF outcome fertilization rates or biochemical pregnancies [ 15 ]. |
| Antioxidant and Infertility | IntechOpen | Ekerhovd E, Brannstrom M, Alexandersson M, Norstrom A: Evidence for nitric oxide mediation of contractile activity in isolated strips of the human Fallopian tube. J Pineal Res 46 1 — HEPES [ 2-hydroxyethyl piperazineethanesulfonic acid] was found to be the most potent protector compared to human tubal fluid media and polyvinyl alcohol against DNA damage occurring in spermatozoa, as determined by plasmid relaxation assay which measures the plasmid DNA damage [ ]. Hypoxic but not anoxic stabilization of HIF-1alpha requires mitochondrial reactive oxygen species. During folliculogenesis, oocytes are protected from oxidative damage by antioxidants such as catalase, SOD, glutathione transferase, paraoxanase, heat shock protein HSP 27, and protein isomerase [ 47 ]. Reactive oxygen species can attack polyunsaturated fatty acids of the cell membrane leading to a chain of chemical reactions called lipid peroxidation and this will lead to decrease structural fluidity of these compounds, thus resulting in loss of integrity of cellular membranes [ 6 ]. |
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