6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Effects of Antiretroviral Therapy on Sperm DNA Integrity of HIV-1-Infected Men

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          HIV-1-affected couples’ desire to have children and free sexual intercourses with the use of pre-exposure prophylaxis for the negative partner has emerged as an alternative option to assisted reproduction in aviremic patients under highly active antiretroviral therapy (HAART). It is already known that sperm quality may be impaired in HIV-infected men. The underlying physiopathological mechanism is still debated. The aim of this study was to evaluate the effects of HAART on sperm DNA fragmentation, comparing HIV-1-infected patients taking HAART versus naïve HIV-1-infected patients. This is a prospective case-control study. Sperm nuclear DNA fragmentation rate was evaluated by the sperm chromatin dispersion test in 77 HIV-infected men: 53 HIV-1 patients receiving HAART (Group 1) versus 24 naïve HIV-1 patients not receiving HAART (Group 2). Complete semen analysis was performed according to WHO 2010 recommendations. Patients with HBV infection or HCV infection coinfections and genital tract infections wre excluded. All the patients did not present any clinical signs of their disease. Seminal parameters were examined in the two groups, showing no significant differences. Increased sperm DNA fragmentation > 30% was demonstrated in 67.9% of patients in Group 1 and 37.5% of patients in Group 2, respectively ( p = .02). A positive but nonsignificant trend toward increased fragmentation was reported with advancing patients’ age. In conclusion, sperm nuclear fragmentation rate is increased in HIV-1-infected patients taking HAART compared to HIV-1 patients not receiving HAART.

          Related collections

          Most cited references45

          • Record: found
          • Abstract: found
          • Article: not found

          The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis.

          Is there an association between high levels of sperm DNA damage and miscarriage? Miscarriage rates are positively correlated with sperm DNA damage levels. Most ejaculates contain a subpopulation of sperm with DNA damage, also referred to as DNA fragmentation, in the form of double or single-strand breaks which have been induced in the DNA prior to or following ejaculation. This DNA damage may be particularly elevated in some subfertile men, hence several studies have examined the link between sperm DNA damage levels and conception and miscarriage rates. A systematic review and meta-analysis of studies which examined the effect of sperm DNA damage on miscarriage rates was performed. Searches were conducted on MEDLINE, EMBASE and the Cochrane Library without any language restrictions from database inception to January 2012. We used the terms 'DNA damage' or 'DNA fragmentation' combined with 'miscarriage', 'abortion' or 'pregnancy' to generate a set of relevant citations. Data extraction was performed by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of relative risks of miscarriage was performed with a random effects model. Subgroup analyses were performed by the type of DNA damage test, whether the sperm examined were prepared or from raw semen and for pregnancies resulting from IVF or ICSI treatment. We identified 16 cohort studies (2969 couples), 14 of which were prospective. Eight studies used acridine orange-based assays, six the TUNEL assay and two the COMET assay. Meta-analysis showed a significant increase in miscarriage in patients with high DNA damage compared with those with low DNA damage [risk ratio (RR) = 2.16 (1.54, 3.03), P < 0.00001)]. A subgroup analysis showed that the miscarriage association is strongest for the TUNEL assay (RR = 3.94 (2.45, 6.32), P < 0.00001). There is some variation in study characteristics, including the use of different assays and different thresholds for DNA damage and the definition of pregnancy loss. The use of methods which select sperm without DNA damage for use in assisted conception treatment may reduce the risk of miscarriage. This finding indicates that assays detecting DNA damage could be considered in those suffering from recurrent pregnancy loss. Further research is necessary to study the mechanisms of DNA damage and the potential therapeutic effects of antioxidant therapy. None.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Significance of mitochondrial reactive oxygen species in the generation of oxidative stress in spermatozoa.

            Male infertility has been linked with the excessive generation of reactive oxygen species (ROS) by defective spermatozoa. However, the subcellular origins of this activity are unclear. The objective of this study was to determine the importance of sperm mitochondria in creating the oxidative stress associated with defective sperm function. Intracellular measurement of mitochondrial ROS generation and lipid peroxidation was performed using the fluorescent probes MitoSOX red and BODIPY C(11) in conjunction with flow cytometry. Effects on sperm movement were measured by computer-assisted sperm analysis. Disruption of mitochondrial electron transport flow in human spermatozoa resulted in generation of ROS from complex I (rotenone sensitive) or III (myxothiazol, antimycin A sensitive) via mechanisms that were independent of mitochondrial membrane potential. Activation of ROS generation at complex III led to the rapid release of hydrogen peroxide into the extracellular space, but no detectable peroxidative damage. Conversely, the induction of ROS on the matrix side of the inner mitochondrial membrane at complex I resulted in peroxidative damage to the midpiece and a loss of sperm movement that could be prevented by the concomitant presence of alpha-tocopherol. Defective human spermatozoa spontaneously generated mitochondrial ROS in a manner that was negatively correlated with motility. Simultaneous measurement of general cellular ROS generation with dihydroethidium indicated that 68% of the variability in such measurements could be explained by differences in mitochondrial ROS production. We conclude that the sperm mitochondria make a significant contribution to the oxidative stress experienced by defective human spermatozoa.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Simple determination of human sperm DNA fragmentation with an improved sperm chromatin dispersion test.

              To improve the sperm chromatin dispersion (SCD) test and develop it as a simple kit (Halosperm kit) for the accurate determination of sperm DNA fragmentation using conventional bright-field microscopy. Method development, comparison, and validation. Medical genetics laboratory, academic biology center, and reproductive medicine centers. Male infertility patients attending the Reproductive Medicine Center. A varicocele patient and a group of nine fertile subjects. None. [1] The quality of chromatin staining in relaxed sperm nuclear halos and tail preservation; [2] SCD scoring reproducibility; [3] comparison with the sperm chromatin structure assay in 45 samples; [4] frequency of sperm with DNA fragmentation after incubation with increasing doses of the nitric oxide donor sodium nitroprusside and in sperm samples for 9 fertile men, 46 normozoospermic patients, 23 oligoasthenoteratozoospermic patients, and a subject with varicocele. The sperm nuclei with DNA fragmentation, either spontaneous or induced, do not produce or show very small halos of DNA loop dispersion after sequential incubation in acid and lysis solution. The improved SCD protocol (Halosperm kit) results in better chromatin preservation, therefore highly contrasted halo images can be accurately assessed using conventional bright-field microscopy after Wright staining. Moreover, unlike in the original SCD procedure, the sperm tails are now preserved, making it possible to unequivocally discriminate sperm from other cell types. The chi2 test did not detect significant differences in the mean number of sperm cells with fragmented DNA as scored by four different observers. The intraobserver coefficient of variation for the estimated percentage of spermatozoa with fragmented DNA ranged from 6% to 12%. There was good correlation between the SCD and the sperm chromatin structure assay DNA fragmentation index (intraclass correlation coefficient R: 0.85; percent DNA fragmentation index mean difference: 2.16 significantly higher for SCD). Using the Halosperm kit, a dose-dependent increase in sperm DNA damage after sodium nitroprusside incubation was detected. The percentage of sperm cells with fragmented DNA in the fertile group was 16.3 +/- 6.0, in the normozoospermic group, 27.3 +/- 11.7, and in the oligoasthenoteratozoospermic group, 47.3 +/- 17.3. In the varicocele sample, an extremely high degree of nuclear disruption was detected in the population of sperm cells with fragmented DNA. The improved SCD test, developed as the Halosperm kit, is a simple, cost effective, rapid, reliable, and accurate procedure, for routinely assessing human sperm DNA fragmentation in the clinical andrology laboratory.
                Bookmark

                Author and article information

                Journal
                Am J Mens Health
                Am J Mens Health
                JMH
                spjmh
                American Journal of Men's Health
                SAGE Publications (Sage CA: Los Angeles, CA )
                1557-9883
                1557-9891
                22 August 2018
                November 2018
                : 12
                : 6
                : 1835-1842
                Affiliations
                [1 ]Unit of Obstetrics and Gynecology, Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli Sacco, Hospital “L. Sacco,” University of Milan, Italy
                [2 ]Centre for Fetal Research Giorgio Pardi, University of Milan, Italy
                [3 ]Statistical and Biometry Unit, Department of Biomedical and Clinical Sciences, Hospital “L. Sacco,” University of Milan, Milan, Italy
                Author notes
                [*]Valeria Savasi, Unit of Obstetrics and Gynecology, Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli Sacco, Hospital “L. Sacco,” University of Milan, Via G.B. Grassi 74, Milan 20157, Italy. Email: valeria.savasi@ 123456unimi.it
                Author information
                https://orcid.org/0000-0002-1476-7689
                https://orcid.org/0000-0003-2648-195X
                Article
                10.1177_1557988318794282
                10.1177/1557988318794282
                6199444
                30132391
                58ee8165-d247-4e0c-b9ec-a4c01d0e0a8b
                © The Author(s) 2018

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 19 March 2018
                : 16 July 2018
                : 22 July 2018
                Categories
                Special section-HIV/AIDS/STIs

                hiv/aids,physiological and endocrine disorders,male infertility,male family planning,sexuality,sexually transmitted diseases/infections

                Comments

                Comment on this article