Marijuana

MJ is the most commonly used recreational drug worldwide 13-15 . It is one of the most commonly abused substances in the USA, where 3.3 of young adults 19-28 years of age use MJ on a daily basis and 54 of people between 26 and 34 have used MJ at least once 16 . Medicinal uses of cannabis date back thousands of years, and both crude smoke and the psychoactive component, delta-9-tetrahydocannabinol (D9-THC), have been used for treating migraine headache, glaucoma, nausea, and anorexia 17 . MJ...

OS and In Vitro Infertility

Reactive oxygen and nitrogen species that lead to OS have a negative impact not only on male fertility in natural conception but also on assisted reproductive technologies (ART) in an in vitro setting. In any ART procedure, there is a risk of oxidative damage from sources such as exposure to ambient air 70 . Other sources of OS in an ART setting include the oocyte, embryo, cumulus cells, and immature sperm cells 6 . In addition, spermatozoa used in any ART procedure originate from an...

Clinical Implications

2.2.5.1 Mitochondrial ROS and DNA Damage A strong marker for oxidative DNA damage is the major oxidized base adduct formed when DNA is subjected to attack by ROS, 8OHdG. Clinically, this marker has been shown to be higher in spermatozoa of subfertile patients 132 . The importance and clinical implications of oxidative DNA damage will be covered in Chap. 11, although it is important to further emphasize the ability of mitochondrial ROS to contribute to nuclear DNA damage. Admittedly mtDNA damage...

The Role of Cytokines in Semen Inflammation

Fertilization Oxidative Stress

The activation of leukocytes at a site of the inflammatory process is strictly connected with both the oxidative burst and the initiation of an immune response directed against an infectious agent. The secretion of cytokines is one of the first signals from the innate host defense to combat inflammation. Proinflammatory cytokines are one of the mediators of the host response to inflammatory reaction. Generated by both the cells of the immune system as well as those of surrounding tissues in...

Studies on EMR and Male Infertility

Within the last decade, there have been several well-designed and executed studies on the effects of mobile phone radiation on spermatozoa, covering three main areas, clinical epidemiological, human (in vitro) and in vivo animal models. The association between RF-EMR and male infertility was initially suggested by an epidemio-logical study in 2001 where it was speculated that differences in fertility parameters from Chinese males in various professions may be due to EMR exposures 52 . More...

Obesity and Male Infertility

Infertility Obesity Mechanism

BMI has been found to be associated with altered sperm parameters in numerous reports. In a recent study investigating factors related to semen quality, the prevalence of infertility in obese men was found to be three times greater than in male partners of couples with idiopathic or female-factor infertility 12 . Moreover, sperm density and total count was shown to have a statistically significant negative correlation to increasing BMI 12 . Another study looked at normozoospermic partners in an...

Mechanism of Penile Erection

Shear Stress Erection

The main mediator of penile erection is nitric oxide (NO). NO is synthesized by two enzymes endothelial NO synthase (eNOS NOS3) and neuronal NO synthase (nNOS NOS1). nNOS-containing (nitrergic) nerve fibers course from the major pelvic ganglia (MPG) and terminate in the penis. eNOS localizes to the vascular and sinusoidal endothelium in the penis 4 . Sensory reflexogenic and psychogenic sexual stimulation activates nNOS, which initiates the erectile response. Sexual stimulation also neuronally...

Physiology of Penile Erection

The penis contains two chambers (the corpora cavernosa), which run the length of the organ, and are surrounded by a membrane (the tunica albuginea). Erection or flaccidity of the penis results from relaxation or contraction, respectively, of smooth muscle cells in the corpora cavernosa. Penile erection is a complex neurovascular process involving relaxation of the corpus cavernosal smooth muscles and vasodila-tion of blood vessels supplying the corpora cavernosa. This is due to both increased...

Potential Therapeutic Role of PARP in Male Infertility

As PARPs play an important role in cell death and apoptosis, they could be good candidates in therapeutic regimens. It was hypothesized that PARP inhibitor causes prevention of DNA repair of malignant cells following exposure to chemotherapy 89 , In cancer patients, the antitumor properties of PARP can preserve fertility even after chemotherapy or radiotherapy 2 . Jha et al. proposed that PARP inhibition can protect sperm against chemically induced injury in vitro 10 . In a recent study by...

Relationship Between Cytokines and Seminal Parameters

Human semen contains a variety of different cytokines and other immunological factors and their effects on semen quality and sperm function are still the subject of debate. There is increasing evidence that many of the cytokines adversely affect spermatogenesis and steroidogenesis 28 . However, there is an ongoing controversy concerning the biological role of particular cytokines in the fertilization process. A lot of studies have indicated the lack of any connection between the cytokine levels...

Cytokines Influence on Steroidogenesis

Cytokines take part in gonadal steroidogenesis (Fig. 9.2). In testis, they are physiologically produced by Sertoli cells and Leydig cells and they regulate cell proliferation as well as steroidogenesis. However, increased concentrations of cytokines may adversely influence cell function. For example, IL-1a may negatively influence expression of regulatory protein steroidogenic acute regulator (StAR) as well as its phosphorylation, thus inhibiting cholesterol translocation to inner mitochondrial...

Clinical Consequences of Oxidative Stress in Male Infertility

Gokul, and Ashok Agarwal Abstract Male infertility affects 40 of infertile couples in the USA and may be attributed to conditions such as varicocele, leukocytospermia, infection, and idiopathic infertility. Such conditions may be associated with elevated levels of reactive oxygen species (ROS), decreased antioxidants, and oxidative stress (OS). OS can lead to male infertility in both an in vitro and in vivo setting. The negative effects of ROS on male fertility present...

Oxidative Stress DNA Damage and Apoptosis in Male Infertility

Said, Constanze Fischer-Hammadeh, Mohammed Hamad, Khaled Refaat, and Mohamad Eid Hammadeh Abstract Oxidative stress, sperm DNA damage, and apoptosis are associated with male infertility as a cause and as a manifestation. Several clinical conditions and laboratory findings may be indicative of the presence of oxidative stress, sperm DNA damage, and apoptosis. The use of standardized assays for the diagnosis of oxidative stress, sperm DNA damage, and apoptosis should be limited to cases...

Apoptosis Oxidative Stress and BPH

An alternative mechanism for BPH may be related to metabolic disturbances. Obesity and elevated fasting glucose are components of the metabolic syndrome 61 Both the obesity and the metabolic syndrome are associated with systemic inflammation and oxidative stress 62 . Inflammation has been previously implicated as a primary stimulus for prostate carcinogenesis 63 , and in the same way, it is possible that BPH represents an alternate, nonmalignant pathway of unregulated prostate growth promoted...

Nox Family of Nadph Oxidases

The NADPH oxidases are a family of enzymes that catalyze electron transfer from cytosolic NADPH to molecular oxygen to generate superoxide as its primary product. To date, seven NADPH oxidase isoforms have been identified in different mammalian cells and tissues 18 . The prototype gp91phox-containing NADPH oxidase possesses cytosolic subunits (p47phox, p67phox, or homologues) and membrane-bound subunits (gp91phox and p22phox) , which form a functional enzyme complex upon activation 16 . NADPH...

Inflammatory Conditions in the Gonad Oxidative Stress

The oxidative stress and lipid peroxidation, which occur in the gonad, are significant factors responsible for male infertility arising from the imbalance between production of reactive forms of oxygen and the efficiency of systems which eliminate Exogenous antioxidants polyphenols, vitamin C, vitamin E and carotenoids Fig. 9.3 Oxidative stress as a link between inflammation and apoptosis. The inflammatory state induces activation of macrophages and release of cytokines leading to free radicals...

Antioxidants A Practical Approach for Treating iOAT

As a multifactor disorder, iOAT presents a clinical challenge in the diagnosis and medical treatment of infertile men. ICSI has enabled iOAT to be circumvented mechanically however, it fails to address the fundamental factors contributing to male factor infertility. Oral supplementation of hormones and antioxidants has been the primary area of focus for pharmacotherapy treatment of iOAT. Significant improvements in sperm concentration, motility, and morphology have been reported 45 . Therefore,...

References

Role of oxidative stress and antioxidants in andrology and assisted reproductive technology. J Androl. 2003 25(1) 5-18. 2. Kenkel S, Rolf C, Nieschlag E. Occupational risks for male fertility an analysis of patients attending a tertiary referral centre. Int J Androl. 2001 24(6) 318-26. 3. Sharlip ID, Jarow JP, Belker AM, et al. Best practice policies for male infertility. Fertil Steril. 2002 77(5) 873-82. 4. Agarwal A, Makker K, Sharma R. Clinical relevance of oxidative stress in male...

Cigarette Smoking

Tobacco plants, like many other plants, will invariably contain certain amounts of lead absorbed from the soil however, lead may also be deposited on the surface of the leaves. The widespread use of lead arsenate as a pesticide on tobacco crops has, in the past, resulted in lead contamination of tobacco products. The effect of tobacco constituents on classical sperm parameters and fertility has been under investigation for decades 47 . Kunzle et al. 48 , when evaluating many men attending a...

Biomarkers for Inflammation in BPH

Inflammation has important association with the pathogenesis, symptoms, and progression of BPH. Then, discovery of a biomarker would be invaluable for monitoring the progress of the disease. There are a number of early candidates and many others are currently being assessed by international research groups. A small study 115 suggested that measurement of serum malondialdehyde (MDA), an index of inflammation and oxidative stress, may be a useful marker in BPH. Serum MDA levels were analyzed in...

Commercial Antioxidants

Several beverages, such as pomegranate juice, red wine, blueberry juice, cranberry juice, orange juice, and green tea, have been touted to have roles in improving erectile function in disease states via their ROS scavenging capacities. In animal models of arteriogenic ED, pomegranate juice decreased oxidative stress and improved, although it did not normalize, erectile function 171, 172 . This beneficial effect of pomegranate juice may be due to its main active ingredients such as polyphenol...

Cytokines as Potential Diagnostic Markers of Male Infertility

The clinical role of evaluation of cytokines participating in urogenital infections inflammations has been recently found to be the important area of interest. The present routine diagnostics of inflammation in the male reproductive tract is mainly based on the determination of leukocyte concentration and microbiological evaluation of the semen. Because the harmful effect of cytokines on spermatozoa is closely connected with the accompanying leukocytospermia, the evaluation of the leukocyte...

Mitochondrial Antioxidants and Fertility

The deleterious effects resulting from the formation of ROS in the mitochondrion are, to a large extent, prevented by various antioxidant systems, and as such, mammalian mitochondria possess a relative abundance of enzymatic and nonenzymatic antioxidants designed to manage and counteract the ROS generated. An in-depth presentation of the literature is well beyond the scope of this chapter however, a brief description is provided to represent the well-characterized ROS scavenging systems that...

Oxidative Stress in Male Reproductive System and ART Outcomes

The quality of the spermatozoa used for ART is crucial to get successful fertilization and pregnancy 126 . Spermatozoa are vulnerable to oxidative stress because their membranes are rich in unsaturated fatty acids 126 and they have no mechanisms for repairing their damaged DNA 127 . This will result in decrease in membrane fluidity and reduce the activity of membrane and ion channels which will end with impaired spermatozoa fertilization capacity. Hammadeh et al. demonstrated that using...

Cryptorhidism Means

Testicular torsion or spermatic cord torsion is the most common genitourinary tract emergency of childhood and probably the second most common surgical emergency in the adolescent age group after acute appendicitis 1-3 . This clinical entity is commonly referred to as the acute scrotum. Of the diseases that cause an acute scrotum, spermatic cord torsion is undoubtedly the most important. Misdiagnosis and inappropriate treatment lead to male factor infertility. Thus, a child presenting with an...

Influence of Cytokines on Sperm DNA and Apoptosis

The poor quality of sperm DNA appears to be one of the important factors affecting male reproductive ability 141 . This has been confirmed by numerous reports in which a high percentage of spermatozoa with fragmented DNA have been found in infertile men when compared to the fertile individuals 142, 143 . In case of inflammation of the genitourinary tract, the redox imbalance is probably the main etiological factor responsible for destructive effects of the inflammatory process on male gametes,...

Mitochondrial ROS and Spermatozoa 2211 Mitochondrial ROS Production

The first reports of mitochondrial ROS generation in mammalian spermatozoa were established in the rabbit using cytochrome c peroxidase assays 26 and an in-depth study in the rat via chemiluminescence 9 . The first analysis of human spermatozoa using the novel MitoSOX Red superoxide fluorescent probe by Koppers et al. 27 indicated that the mitochondria was indeed a major source of ROS and oxidative stress observed in defective human spermatozoa. The level of mitochondrial ROS generation within...

The Role of Obesity in ROS Generation and Male Infertility

Kashou, Stefan S. du Plessis, and Ashok Agarwal Aim To discuss the relationship between obesity and male infertility, specifically exploring the role of reactive oxygen species (ROS) production in obesity and the subsequent generation of oxidative stress, as well as abnormal hypothalamus-pituitary-gonadal regulation associated with obese males. Results Both enhanced ROS generation and abnormal hormonal regulation due to obesity are strongly correlated to suboptimal semen quality and,...

Effect of Oxidative Stress on ART Outcome

Mohamad Eid Hammadeh, Mohammed Hamad, Khaled Refaat, Tamer M. Said, and Constanze Fischer-Hammadeh Abstract Oxidative stress is a condition that causes cellular damage including destruction of all cellular components including lipids, proteins, nucleic acids, and sugars. It affects negatively the quality of oocytes, sperm oocyte interaction, implantation, and early embryo development which influence the success of pregnancy. Many events related to infertility may occur due to OS in the female...

Effect of Varicocelectomy on Oxidative Stress

Varicocelectomy is the most common urological procedure for male factor infertility. In most of the published studies, varicocele repair has been associated with an improvement in semen parameters and spontaneous pregnancy rates, although the data remain controversial 81, 82 . Varicocele repair may improve pregnancy outcomes after assisted reproduction technologies (ARTs) 83, 84 . There is now evidence to show that varicocelectomy may reduce seminal oxidative stress and this provides another...

Role of Caspase PARP and Oxidative Stress in Male Infertility

Abstract The etiology and pathogenesis of male infertility remain not well defined. Oxidative stress has been identified as one of the major causes of male infertility. Integrity of the sperm DNA, which could be caused by oxidative stress, also plays an important role in vivo and in vitro male fertility. Poly (ADP-ribose) polymerase (PARP) is a DNA repair enzyme that has been demonstrated in mature spermatozoa and fertile men. PARP becomes activated in an attempt to repair oxidative DNA strand...

Targeting Nadph Oxidase 281011 PDE5 Inhibitors

PDE5 inhibitors, e.g., sildenafil citrate, tadalafil, vardenafil hydrochloride, promote penile erection in response to sexual stimulation by inhibiting PDE5-catalyzed degradation of cGMP. They are widely accepted as an efficacious option for the treatment of ED in most, but not all, cases 6 . Recently, interest has been generated in the additional effects of PDE5 inhibitors on preventing formation of ROS and inhibition of ROS-mediated PDE5 upregulation in the penis. Several animal studies have...

Identification of Sperm Oxidative Stress from Clinical History

Male Infertility Causes Mnemonics

The various causes of male infertility are outlined in Fig. 16.1, with the majority of these sources of sperm dysfunction being relatively easy to identify through history alone. The mnemonic Testicular is a helpful aide-memoire for recalling the underlying causes of male infertility, with sperm oxidative stress playing a pivotal role in the majority of these male infertility pathologies. Exposure to oxins such as heavy metals through the manufacture of lead acid batteries or soldering fumes is...

Pathophysiology of Varicocele

The true effect of varicocele on testicular function and male fertility remains unknown. Although numerous studies have clearly demonstrated an association between varicocele and reduced male reproductive function (e.g., poor semen parameters, infertility), most varicocele studies involve highly selected populations (e.g., infertile men), making it difficult to ascertain the role of varicoceles in male infertility. Moreover, the lack of reliable end-points for measuring fertility represents...

Diagnosis of OS and ROS Levels

The chemiluminescence assay is a direct method of quantifying extracellular ROS levels. This assay uses lucigenin and luminol to assess the generation of the superoxide anion and hydrogen peroxide 76 . Lucigenin detects superoxide anion, while luminol detects hydrogen peroxide. These agents are oxidizable substrates that react with certain oxygen species in order to measure levels of ROS. The chemilumines-cence assay or calorimetric assay can also be used to measure the total antioxidant Fig....

Andor teratozoospermia

Any of the following combination * 1 factor A + 1 factor B 1 factor A + 1 factor C Prostate, seminal vesicles, and or epididymis ultrasound abnormalities (by scrotal and transrectal ultrasound scans) In case of prostatitis alone, examine the prostatic fluid Abnormal prostatic expression fluid and or abnormal urine after prostatic massage Positive history for urinary infection, epididymitis, and or sexual transmitted diseases Thickened or tender epididymis, tender vas deferens, and or abnormal...

Clinical Conditions of Exacerbated Oxidative Stress That Lead to Sperm DNA Damage

Clinical varicocele has been associated with an increase in free radical production including both oxygen and nitrogen-derived radical species 34, 35 . Nitric oxide production is proportional to the severity of varicocele 36 and patients with varicocele have increased levels of 8-oxo-guanosine (8-OHdG) in leukocyte DNA indicating oxidative damage 37 . Saleh et al., using the Sperm Chromatin Structure Assay (SCSA) test, reported a significant increase in the extent of sperm DNA damage in...

Sperm Oxidative Stress and DNA Damage

From what is currently known about sperm cell damage and dysfunction, there is certainly scope for RF-EMR to contribute to this affliction. The three main types of cellular damage which can account for the adverse observations made are membrane, protein and DNA damage. The factors responsible for contributing to this damage in the male germ line can be grouped into several categories. Quality of spermatogenesis defines the susceptibility of cells to damage 23 . Biological factors including diet...

Abnormal HPG Regulation

Although several mechanisms that parallel obesity to infertility have been proposed, many remain ambiguous and relatively undefined. Studies indicate that the central factor linking the mechanisms associated with obesity and infertility is an abnormal regulation of the HPG axis, as well as the previously discussed OS. The HPG axis responds to fluctuations in hormones causing a range of widespread and local effects on the body and aspects of reproduction. Excess fat accumulation can impair the...

Idiopathic Oligoasthenoteratozoospermia

IOAT is a complex medical condition that affects approximately 30 of all infertile men and is the most common cause of male infertility 16, 17 . As a three-part disorder, low sperm concentration and motility and morphologically abnormal sperm characterize iOAT. Three classifications have been put into place to evaluate the severity of the disease (1) isolated astheno teratozoospermia (no alteration in sperm concentration) (2) moderate (sperm concentrations between < 20 x 106 mL and > 5 x...

Contributors

Ashok Agarwal, PhD Center for Reproductive Medicine, Cleveland Clinic, Lerner College of Medicine, Cleveland, OH, USA R. John Aitken, PhD, ScD Department of Biological Sciences, University of Newcastle, Callaghan, NSW, Australia Naif Al-hathal, MD Department of Surgery, St. Mary's Hospital, Montr al, QC, Canada Juan G. Alvarez, MD, PhD Department of Male Infertility, Centro Androgen, La Coruna, La Coruna, Spain Mark A. Baker, PhD Department of Environmental and Life Science, University of...

Experimental Testicular Torsion and Antioxidant Therapy

Under normal condition, free radicals are produced and their effects are counterbalanced by the endogenous antioxidant system. When ROS generation exceeds the defense mechanisms' capacity to control, oxidative stress is occurred and contributes to reversible or irreversible cell damage 7, 140 . All living aerobic cells are normally exposed to some ROS, but if ROS levels rise, oxidative stress may occur, which results in oxygen and oxygen-derived oxidants, and in turn increases the rates of...

Testicular Torsion IR Injury in Testis and Oxidative Stress

The mechanism of tissue damage due to I R is common to other organs such as the brain, heart, kidneys, and testis. The primary pathophysiologic event in testicular torsion is ischemia followed by reperfusion thus, testicular torsion detorsion is I R injury to the testis 7 . I R also induce morphological and biochemical changes by both ischemia and reperfusion of the tissues and induce germ cell-specific apoptosis through cell membrane lipid peroxidation, protein denaturation, and DNA damage....

Identification of an Infection

Biochemical evidence has shown that in males with clinically silent genital tract infections, the prostate and seminal vesicles are the organs predominantly affected and targeted by inflammation 60 . The primary role of the seminal vesicles is to provide high concentrations of fructose to the seminal plasma and is vital to the functional integrity of spermatozoa as it is the major source of glycolytic energy in order to maintain motility 18 . The reference value for normal concentrations of...

Lessons from the Mouse GPx Knockout Models

n 2009, the group of Marcus Conrad (Germany) generated a transgenic mouse model in which the mGPx4 was disrupted 52 by introducing an in-frame transla-tional stop into the mitochondrial leader sequence of mGPx4. Analysis of this model revealed that mGPx4- mice are viable, in contrast to early embryonic lethality recorded in the GPx4 ' mice in which the somatic isoform (cGPx4) as well as the two sperm-specific variants, mGPx4 and snGPx4, were absent 72, 73 . Interestingly, the mouse mGPx4-...

Oral Antioxidant Therapy

As outlined in Chap. 23, many studies have been conducted examining the effect of a wide variety of different antioxidant combinations on sperm function and pregnancy outcome. Table 16.2 summarises the outcomes of the various antioxidant treatment regimes tested in a placebo controlled setting. In January 2011, the Cochrane collaboration, widely perceived as the definitive authority on evidence-based medicine, published a review on the effect of oral antioxidant therapy on sperm quality and...

How to Correctly Diagnose MAGI

Conventional WHO criteria for MAGI (Fig. 25.1) should be integrated with the ultrasound exploration of the male accessory glands and an accurate leukocyte assessment (by immunocytochemistry). Therefore, we propose an algorithm for the assessment of MAGI based on sequential levels (Fig. 25.2). Each level includes relative processes broken down into specific actions and outcomes. Table 25.4 Conventional sperm parameters, seminal leukocyte concentration, and basal and fMLP-stimulated radical...