Effects of Varicocelectomy on Sperm DNA Fragmentation, Mitochondrial Function, Chromatin Condensation, and Apoptosis

Section of Endocrinology, Andrology, and Internal Medicine and Master in Andrological, Human Reproduction, and Biotechnology Sciences, Department of Internal Medicine and Systemic Diseases, University of Catania, Catania, Italy.
Journal of Andrology (Impact Factor: 2.47). 06/2011; 33(3):389-96. DOI: 10.2164/jandrol.111.013433
Source: PubMed


The aim of this study was to evaluate conventional semen parameters (density, morphology, and progressive motility) and the flow-cytometric parameters of DNA fragmentation, mitochondrial membrane potential, phosphatidylserine externalization, and chromatin compactness in patients with varicocele before and after varicocelectomy. Thirty men (26.5 ± 3.2 years old, range 20-32 years) with oligoasthenoteratozoospermia and grade 3 left varicocele were selected (without other causes of male infertility). Each of them underwent sperm analysis and flow cytometric evaluation before and 4 months after subinguinal microsurgical varicocelectomy (SMV). After varicocelectomy, men had significantly higher sperm density, progressive motility, and normal forms compared with baseline. They also had a significantly lower percentage of spermatozoa with low mitochondrial membrane potential. After SMV, they showed a significantly lower percentage of spermatozoa with phosphatidylserine externalization, an early sign of apoptosis. Significantly decreased percentages of spermatozoa with abnormal chromatin compactness and spermatozoa with DNA fragmentation were found after SMV compared with baseline. Subinguinal microsurgical varicocelectomy improves sperm function in oligoasthenoteratozoospermia secondary to grade 3 left varicocele. Improvements are seen in conventional parameters and biofunctional parameters not routinely evaluated.

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Available from: Aldo E. Calogero, Sep 16, 2014
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    • "Therefore, the absence of sub-G1 accumulation in C2-ceramide-treated H1299 at 24 h treatment may be due to the detection timing. Furthermore, chromatin condensation was thought to be one of hallmarks in apoptotic cells [32,33]. However, some study indicated that certain stresses such as heat shock may induce a non-apoptotic chromosome condensation [34]. "
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    ABSTRACT: The anticancer effects of ceramide have been reported in many types of cancers but less in lung cancer. In this study, we used C2-ceramide to further investigate its possible anticancer effects and mechanisms on non-small cell lung cancer (NSCLC) H1299 cells. The result of cell proliferation in terms of trypan blue assay showed high dose of C2-ceramide inhibited cell survival after 24 h treatment. The flow cytometry-based assays indicated the effect of apoptosis, chromatin condensation, and G1 arrest in terms of Annexin V/propidium iodide (PI), DAPI, and PI stainings, respectively. Moreover, the decreased protein level of p-Akt, p-NFkappaB, survivin and cyclin A2 were detected by Western blot assay. Taken together, these results indicated the antiproliferative effect of C2-ceramide is majorly responsible for cell apoptosis in lung cancer H1299 cells.
    Cancer Cell International 01/2014; 14(1):1. DOI:10.1186/1475-2867-14-1 · 2.77 Impact Factor
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    • "As the most frequently remediable cause of male infertility , varicoceles are characterised by the dilatation of the veins of the pampiniform plexus within the spermatic chord, causing stasis and increased pressure (Greenfield et al., 2002). Varicoceles occur in approximately 40% of men with primary infertility and 71% of men with secondary infertility (La Vignera et al., 2012). Oxidative stress is one of the mechanisms deemed responsible for the pathophysiology of varicoceles (Agarwal et al., 2009). "
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    ABSTRACT: To analyse the levels of an indirect marker of ROS-induced lipid peroxidation [i.e. malondialdehyde (MDA)] in both testes and the levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase inhibitor-1 (TIMP-1) in the left testis after induction of varicocele and investigated the impact of micronised purified flavonoid fraction (MPFF) on these markers. Forty-nine adolescent (6-week-old) male Wistar rats were included in this study. The rats were divided into seven groups as follows:Group-1, control; Group-2, sham; Group-3, left varicocele-induced; Group-4, varicocele + varicocelectomy + MPFF-treated (for 4 weeks); Group-5, varicocele + MPFF-treated (for 8 weeks); Group-6, varicocele-induced and 4 weeks later, MPFF-treated (for 4 weeks); and Group-7, varicocele + varicocelectomy. MDA was measured in the tissues of both testes using the thiobarbituric acid reactivity method. The ELISA method was used for the quantification of MMP-2, MMP-9 and TIMP-1 in the left testicular tissue. The levels of MDA were significantly higher in the varicocele group than in the other groups. The MDA levels in the left testicular tissues of Group-7 were significantly higher than those of Group 4 (P = 0.03). In the varicocele group, the MMP-2 and MMP-9 levels decreased, whereas the levels of TIMP-1 increased. The tissue levels of MMP-2 in Groups 4, 5 and 7 were significantly higher than those in Group 1 (P < 0.05).
    Andrologia 04/2013; 46(4). DOI:10.1111/and.12091 · 1.63 Impact Factor
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    • "The management of infertile men with increased sperm DNA damage remains high, particularly in varicocele individuals. Some studies have reported that sperm DNA fragmentation to be significantly higher in varicocele individuals compared to those with normal semen parameters (50 , 61 ). Furthermore, DNA damage is associated with fertilization rate, spontaneous pregnancy, and pregnancy outcome post ART (62 , 63 ). "
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    ABSTRACT: Varicocele is considered as one of the main etiologies of male infertility. Along with altered semen parameters, increased DNA fragmentation is believed to play an important role in varicocele-induced infertility. DNA damage may result from intra- or extra-testicular factors. Among these, apoptosis, abnormal chromatin packaging and oxidative stress are the most researched and are addressed in this review. Significant evidence suggests that varicoceles have a harmful effect on testicular function and a varicocelectomy not only prevents progressive decline in testicular function, but also reverses the damage. However, the degree to which varicocele repair improves pregnancy rates and the success of assisted reproductive technology (ART) remains controversial. Therefore, the role of varicocele repair on DNA fragmentation is also discussed.
    International journal of fertility & sterility 12/2012; 6(3):141-146. · 0.47 Impact Factor
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