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Ready: Male Infertility Contemporary Clinical Approaches Andrology Art And Antioxidants
Reset Pincode. Submit a Review. JK Rowling. Home Male Infertility: Contemporary Clinical Click on below image to change. Click on image to Zoom. Average Rating. Submit Review Submit Review. It is possible that excessive intake of some of these antioxidants, especially in combination, may cause other deleterious side effects, and their use needs to be carefully monitored.
Table 1 lists dietary requirements and recommended daily doses of some of the antioxidants.
However, its membrane concentration is very low, usually equal to or less than 0. Nevertheless, under normal conditions oxidation of membrane lipids and proteins does not occur and vitamin E deficiency is seldom found in adult humans. This is mainly due to the vitamin E cycle Figure 2. Vitamin E acts catalytically, being efficiently reduced from its free radical quenching form back to its native state. The presence of a reductant, either hydrophilic as vitamin C or thiols or lipophilic as ubiquinol , causes the vitamin E radical to be regenerated. During nonenzymatic recycling pathway for vitamin E regeneration that occurs in membranes, vitamin C reduces chromanoxyl radicals to recycle vitamin E and eventually being itself consumed by the process Packer, The efficiency of such transfer depends on the concentration of ubiquinol.
Thus, ubiquinol is also a partner with vitamin E in protecting membranes against oxidation, by enhancing the antioxidant activity of vitamin E through recycling. Vitamin C or ubiquinone alone in vitamin E deficiency does not enhance such protection against membrane peroxidation. Thus, vitamin E will be lost only when these backup systems, either in the aqueous or membrane domains, become rate limiting. At this point, increased rates of lipid and protein oxidation, destruction of membrane function, and inactivation of membrane enzymes and receptors will accompany the loss of vitamin E.
Thus, vitamin E not only has an antioxidant action but also acts as a biological response modifier. This vitamin E cycle provides a clear example of a synergistic effect and nature's amazing way of recycling. Health status, lifestyle, diet, and environment markedly influence the requirements for vitamin E. Although demonstrable vitamin E inadequacy in apparently healthy adults is rare, vitamin E requirements may vary fivefold in individuals, depending on the dietary intake of polyunsaturated fat, tissue composition, the steady state concentrations of other interactive antioxidants in tissues, and genetic factors.
Effects of free radicals on male fertility and available treatment
The concept of vitamin E recycling may prove to be crucial in the development of new strategies for the treatment of acute and chronic conditions involving oxidative stress, especially sperm damage in case of infertility. Because vitamin E and other antioxidants prevent or minimize oxidative damage in biological systems, the key question is how adequate the antioxidant defense should be to protect the body from excessive free radical concentrations. During leukocytospermia, the superoxide anion produced by leukocytes is an oxygen radical that along with high levels of inflammatory chemokines may be important for bacterial killing Rajasekaran et al, Because during ART procedures spermatozoa are washed and leukocyte contaminants are removed, it is debated whether use of such antioxidant supplementation may have additional benefits, especially in the presence of HSA in various culture media.
HSA itself is a strong antioxidant Aitken et al, ; Armstrong et al, Besides, unexpectedly elevated intracellular concentrations of vitamin E may have unknown adverse effect on various physiological processes as well as ART outcome. Thus, indiscriminate use of megadoses of vitamin E and other antioxidants both in vitro and as dietary supplements should be carefully monitored.
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Table 2 describes some potent antioxidants and their recommended daily intake; beyond that, caution is desired Coles, Further in vivo and in vitro research is required before one can be optimistic about a role for antioxidants in the treatment of infertile men. However, the results vary in different ART facilities. Discontinuous Percoll density gradient Also, the addition of medium before liquefaction could inhibit the binding of bacteria to the sperm surface and subsequently diminish DNA damage caused by ROS.
On the other hand, many factors play a role in generating ROS during ART that induce spermatozoa damage when processed in vitro. These include leukocytes, abnormal spermatozoa, transition metals present in the culture medium, and centrifugation steps. Considering this fact, it is surprising to find that in vitro culture of testicular spermatozoa does not increase their susceptibility to DNA damage. Sperm chromatin is a very complex structure, and its capability to decondense is one of the essential criteria for considering a spermatozoon to be fertile.
University of Melbourne / Online Boo
DNA integrity in sperm is essential for the accurate transmission of genetic information and, in turn, the maintenance of good health in future generations. It is an independent measure of sperm quality that provides better diagnostic and prognostic capabilities than standard sperm parameters for male fertility potential. Several methods are currently used to assess DNA damage. For such evaluations, the amount of ROS detected, rather than the ROS generated, will represent a more physiological assessment of oxidative stress Krausz et al, ; Sikka et al, LPO is the most extensively studied manifestation of oxygen activation in biology.
Formation of MDA can be assayed by the thiobarbituric acid reaction, which is a simple and useful diagnostic tool for the measurement of LPO for in vitro and in vivo systems Taourel et al, DNA in spermatozoa with abnormal chromatin structure shows increased red fluorescence Evenson et al, In a recent study by Saleh and Agarwal , semen samples were obtained from a randomly selected group of infertile men with a history of infertility of more than 1 year.
Apoptotic spermatozoa were identified by the expression of phosphatidylserine on the outer surface of the plasma membrane. Their results supported the recent hypothesis of a significant role of apoptosis in the pathogenesis of sperm nuclear DNA damage in men who failed to initiate a pregnancy after assisted reproductive techniques. Such an increase may be related to high levels of seminal oxidative stress presumably caused by prostatitis leading to leukocytospermia that can be easily detected microscopically Muller et al, The data were used as a predictor of IUI success Molina et al, A growing body of evidence suggests that low seminal total antioxidant capacity TAC is related to male infertility Smith et al, ; Lewis et al, ; Sharma et al, ; Sikka, The enhanced chemiluminescence assay, however, is the most commonly used method for measuring TAC in seminal fluid Lewis et al, ; Sharma et al, ; Kobayashi et al, ; Pasqualotto et al, However, this assay is cumbersome, requires a luminometer, and is often not readily available in a physician's office.
Another technique based on colorimetric assay has been recently described for estimating the TAC in human seminal plasma Said et al, Antioxidants in the sample suppress this color production to a degree that is proportional to their concentrations. Another assay for measuring TAC is by monitoring the oxygen radical absorbance capacity.
However, that requires a fluorescence detector takes a longer time than the colorimetric assay. There is a lack of consensus in the literature regarding what are normal TAC values in seminal plasma despite the strong correlation between low levels of seminal TAC and male infertility. Therefore, the standardization of any simple and inexpensive assay should be considered the first step to reach such a consensus. Once an oocyte is retrieved into the Petri dish during processing for ART, it becomes very susceptible to oxidative damage. Depletion of the intracellular glutathione pool may further render the oocyte vulnerable to oxidative stress and incapable of decondensing the sperm nucleus, resulting in ART failure.
Because oxygen is toxic to the embryo, an increase in oxidative stress will have a significant impact on the developmental potential of the mammalian embryo. This suggests that the excessive generation of ROS by the defective human embryo can similarly induce apoptosis with demonstrable nuclear changes typical of apoptotic cells.
The culture media frequently used by such facilities are usually supplemented with antioxidants eg, HSA , and as such the antioxidant capacity in the media can be easily monitored in the laboratory. Paszkowski and Clarke showed that the culture media in which viable human embryos were maintained retained the antioxidant activity, but the media recovered from incubations involving fragmenting defective human embryos showed a significant loss of antioxidant activity with time.
This presumably confirms the hypothesis that the intrinsic generation of excess ROS will result in increased oxidative stress leading to failure in the normal development of embryo. It is not clear whether additional supplementation of specific antioxidants during these ART procedures will combat this oxidative stress and help improve fertilization process, embryo quality, and better success rate. Once confirmed, frequent sampling of a small amount of culture media to monitor antioxidant capacity can provide the basis of a simple noninvasive technique for assessing progress in embryo quality in ART programs especially prior to implantation.
Thus, understanding of the role of these antioxidants is at present a very challenging area to focus in an ART laboratory and clinical practice. Poor motility of sperm samples retrieved after cryopreservation, electroejaculation, and vibratory stimulation and in idiopathic infertility patients with genitourinary inflammation has been associated with low success rate after IUI.
Sperm cryopreservation continues to gain importance in assisted reproduction, especially for donor programs and for patients having AIDS, cancer, irradiation, vasectomy, and other aging issues who later desire to have children. Men with spinal cord injury who desire children have invariably low sperm motility in their samples collected from vibratory stimulation or electroejaculation. Several reports suggest improvement in sperm motility and progression by use of many biological or pharmacological stimulants in vitro.
Thus, with such stimulated sperm samples, IUI should be performed within 1—2 hours of stimulation and washing procedures. Besides timing, female fertility status and number of progressively motile spermatozoa used for insemination for IUI more than 1 million sperm or IVF —20 sperm under mineral oil are other major critical factors for ART success in presence of such sperm stimulants. Although an ART laboratory may demonstrate normal parameters on standard semen analysis, defective sperm function is the most prevalent cause of idiopathic male infertility and a difficult condition to treat.
Many sperm stimulation protocols have been described to improve the success rate for these procedures. However, timing of insemination, number of progressively motile sperm eg, more than 1 million for IUI and about 10 to 20 for IVF , and female fertility status are important factors to be considered for such success. Spermatozoa and oocytes possess an inherent but limited capacity to generate ROS, which may help the fertilization process. How this oxidative stress affects interaction of sperm with the ovum and causes embryo toxicity is still unknown. Increased oxidative damage to sperm membranes, proteins, and DNA is associated with alterations in signal transduction mechanisms that affect fertility.
A variety of defense mechanisms encompassing antioxidant enzymes SOD, catalase, glutathione peroxidase, and reductase , vitamins E, C, and carotenoids , and biomolecules glutathione and ubiquinol are involved in biological systems. A balance between the benefits and risks from ROS and antioxidants both in vivo and in vitro appears to be necessary for the survival and normal reproductive functioning. An assay system for the evaluation of OSS may aid the clinician in the assessment of fertility status of both male and female partners.
Determination of this OSS value will also theoretically identify the subgroups of responders and nonresponders to any putative antioxidant therapy. Most dietary antioxidants appear to have only modest physiological effects. Although the therapeutic use of such antioxidants appears attractive with minimal side effects, the proper multicenter clinical trials are required to determine efficacy and any reproductive toxicity before clinicians could recommend such therapeutic alternatives.
The key unanswered question pertaining to their usage is to find out how much is success and beyond that it becomes excess. Volume 25 , Issue 1. The full text of this article hosted at iucr. If you do not receive an email within 10 minutes, your email address may not be registered, and you may need to create a new Wiley Online Library account.
If the address matches an existing account you will receive an email with instructions to retrieve your username. Journal of Andrology Volume 25, Issue 1. Free Access.
Suresh C. Search for more papers by this author. Tools Request permission Export citation Add to favorites Track citation. Share Give access Share full text access. Share full text access. Please review our Terms and Conditions of Use and check box below to share full-text version of article. Figure 1 Open in figure viewer PowerPoint. Peroxidative Damage to Spermatozoa Peroxidative damage initiated by high ROS generation during oxidative stress as seen in the spermatozoa of infertile men is associated with not only a loss of membrane function, but also the appearance of damage to the DNA located in the sperm head in such patients, leading to a high incidence of DNA strand breaks Ernster, ; Evenson et al, ; Agarwal and Said, Figure 2 Open in figure viewer PowerPoint.
Pathways of membrane lipid peroxidation and vitamin E recycling. Oxidative stress and sperm membrane lipid peroxidation Spermatozoa, unlike other cells, are unique in structure, function, and very susceptible to damage by ROS Alvarez et al, ; Rao et al, At present, the key questions in this direction that remain unanswered are the following: Is active apoptosis present in the spermatozoa in semen, and if yes, what is the molecular mechanism of such an apoptotic pathway?
Is apoptosis a significant contributor to DNA damage in the seminal spermatozoa?