Apoptosis and DNA damage in human spermatozoa

Aitken, R. John; Koppers, Adam J.

doi:10.1038/aja.2010.68

Cited by 292 publications

(207 citation statements)

References 78 publications

(83 reference statements)

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“…Several studies demonstrated the impact of sperm DNA damage and its correlation with clinical endpoints including fertilization rates, embryonic development, implantation, pregnancy and miscarriage rates [33][34][35].…”

Section: Discussionmentioning

confidence: 99%

High Pregnancy and Implantation Rates Can Be Obtained Using Magnetic-Activated Cell Sorting (MACS) to Selection Spermatozoa in Patients with High Levels of Spermatic DNA Fragmentation

Ferreyra¹

2014

JFIV Reprod Med Genet

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Purpose: DNA fragmentation in spermatozoa has been associated with poor semen quality, low fertilization rates, impaired preimplantation development, and high miscarriage rates. The objective of this study was to evaluate the effects of the use of non-apoptotic MACS-selected spermatozoa in ICSI cycles, compared to those ICSI cycles in patients with normal sperm DNA fragmentation.Methods: A total of 134 cycles of ICSI were included in the study. The study group consisted of patients with high DNA fragmentation and their spermatozoa were selected by MACS (n=57); and the control group, of patients with normal DNA fragmentation and their spermatozoa were selected by classic morphological characteristics. The fertilization rate, cleavage rate, embryo quality, pregnancy rate (PR), implantation rate (IR) and miscarriage rate (MR) were compared between groups.Results: There was no difference in the fertilization rate (74.5 and 76.5%), cleavage rate and good embryo quality at Day 3 (98.3 and 89.1%; 88.4 and 83.7%) or blastocyst formation rate (50.8 and 41.1%) for the study and control groups, respectively. PRs, IRs and MRs were similar for the study group compared to the control group (PR: 63.2 versus 45.5%; IR: 37.4 versus 28.1%; MR: 8.3 versus 17.1). The women were distributed into three groups: <35 years, 35-39 years and ≥ 40 years. Pregnancy, implantation and miscarriage rates were similar in the three evaluated groups (P: NS). Conclusions:By selecting non-apoptotic sperm by MACS, we can achieve very acceptable pregnancy and implantation rates; being a good option for couples with high sperm DNA fragmentation and repeated assisted reproduction failures. Citation: García-Ferreyra J, Villegas L, Romero R, Zavala P, Hilario R, et al. (2014) High Pregnancy and Implantation Rates Can Be Obtained Using Magnetic-Activated Cell Sorting (MACS) to Selection Spermatozoa in Patients with High Levels of Spermatic DNA Fragmentation. JFIV Reprod Med Genet 3: 133. doi:10.4172/2375-4508.1000133 Several studies reported an improvement in fertilization rates [15,16] and embryo quality [17][18][19] because the best sperms were selected using MACS compared to standard selection methods. On the other hand, Gil et al. [20] showed that the implantation and miscarriage rated did not vary between MACS or standard sperm selection methods; however, they did observe an improvement in pregnancy rates. High Pregnancy and Implantation Rates CanIn this study, we evaluated the effects of using MACS as a sperm selection technique in patients with high DNA fragmentation compared with patients with normal DNA fragmentation and determine the efficacy of such technique in the hopes of improving ART success rates. Materials and Methods PatientsIn this study, we analyzed 134 cycles of ICSI that were done between March 2012 and April 2014 at FERTILAB Laboratory of Assisted Reproduction (Lima, Peru), all approved by the Institutional Review Board (IRB) and the corresponding Ethics Committee. Written consent was obtained from all patients and their...

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Section: Discussionmentioning

confidence: 99%

High Pregnancy and Implantation Rates Can Be Obtained Using Magnetic-Activated Cell Sorting (MACS) to Selection Spermatozoa in Patients with High Levels of Spermatic DNA Fragmentation

Ferreyra¹

2014

JFIV Reprod Med Genet

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“…2 ), hydrogen peroxide (H 2 O 2 ) and a highly toxic hydroxyl radical (OH?). [1][2][3][4] Spermatozoa are particularly susceptible to damage by processes involving free radicals for several reasons. The sperm membrane is rich in polyunsaturated fatty acids, which provide a sufficient fluidity of the sperm membrane to allow it to participate in the membrane fusion events that characterize fertilisation.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa

Gavella¹,

Lipovac²

2013

Asian J Androl

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This article summarizes the available evidence on the efficacy of gangliosides to reduce the degree of reactive oxygen species (ROS)-mediated damage. The antioxidative efficacy of exogenous gangliosides in protecting different cells encouraged us to examine their ability to protect human spermatozoa. Gangliosides are sialic acid-containing glycosphingolipids with strong amphiphilic character due to the bulky headgroup made of several sugar rings with sialic acid residues and the double-tailed hydrophobic lipid moiety. The amphiphilicity of gangliosides allows them to exist as micelles in aqueous media when they are present at a concentration above their critical micellar concentration. The protective effect of ganglioside micelles on spermatozoa is believed to stem from their ability to scavenge free radicals and prevent their damaging effects. In our study, we particularly focused our attention on the protective effect of ganglioside micelles on DNA in human spermatozoa exposed to cryopreservation. The results indicate that ganglioside micelles can modulate the hydrophobic properties of the sperm membrane to increase tolerance to DNA fragmentation, thus protecting the DNA from cryopreservation-induced damage. Further actions of ganglioside micelles, which were documented by biochemical and biophysical studies, included (i) the modulation of superoxide anion generation by increasing the diffusion barrier for membrane events responsible for signal translocation to the interior of the cell; (ii) the inhibition of iron-catalysed hydroxyl radical formation due to the iron chelation potential of gangliosides; and (iii) inhibition of hydrogen peroxide diffusion across the sperm membrane.

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“…Another way to look at this problem is to address if, and how, sperm are capable of confessing their errors/flaws externally, 41 which may allow non-invasive sperm selection, e.g., in response to DNA damage 42 . However, it remains to be seen whether such biomarkers do exist or if the heterogeneity of spermatozoa is too great for such selection methods to be applicable to every patient.…”

Section: Sperm Function Testing and Icsimentioning

confidence: 99%

Diagnostic tools in male infertility—the question of sperm dysfunction

Barratt¹,

Mansell²,

Beaton³

et al. 2010

Asian J Androl

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Sperm dysfunction is the single most common cause of infertility, yet what is remarkable is that, there is no drug a man can take or add to his spermatozoa in vitro to improve fertility. One reason for the lack of progress in this area is that our understanding of the cellular and molecular workings of the mature spermatazoon is limited. However, over the last few years there has been considerable progress in our knowledge base and in addressing new methods to diagnose sperm dysfunction. We review the current state of the field and provide insights for further development. We conclude that: (i) there is little to be gained from more studies identifying/categorizing various populations of men using a basic semen assessment, where an effort is required in making sure the analysis is performed in an appropriate high quality way; (ii) technological development is likely to bring the reality of sperm function testing closer to implementation into the clinical pathways. In doing this, these assays must be robust, cheap (or more appropriately termed cost effective), easy to use and clinically useful; and (iii) clinical necessity, e.g., the need to identify the highest quality spermatozoon for injection is driving basic research forward. This is an exciting time to be an andrologist and, likely, a fruitful one. Keywords: gamete biomarker; male fertility; sperm biomarker; sperm dysfunction INTRODUCTION Infertility is a significant global problem affecting approximately 80 million (1:7) couples worldwide. 1 In a landmark study by Mike Hull and colleagues, in which a representative British population was studied, sperm dysfunction (lacking 'normal' function) was identified as the single most common cause of infertility. 2 Subsequent studies have confirmed these observations 3 and highlighted dysfunctional cells in men with 'normal' semen parameters and conversely normal sperm function in oligozoospermic men. 4 What is remarkable is that, for this group, there is no drug a man can take or add to his spermatozoa in vitro to improve fertility. The only option is assisted reproductive technology (ART) which usually consists of a graduation of treatment depending on severity, i.e., intrauterine insemination for mild, in vitro fertilisation (IVF) for moderate and intracytoplasmic sperm injection (ICSI) for men with severe sperm dysfunction. One reason for the lack of progress in this area is that our understanding of the cellular and molecular workings of the mature spermatazoon is limited. However, over the last few years there has been considerable progress in our knowledge base and in addressing new methods to diagnose sperm dysfunction. The purpose of this paper is to review the current state of the field and provide insights for further development. The initial focus is on the value of semen analysis as a clinical tool with the discussion progressing to examining sperm dysfunction in detail.

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Apoptosis and DNA damage in human spermatozoa

Cited by 292 publications

References 78 publications

High Pregnancy and Implantation Rates Can Be Obtained Using Magnetic-Activated Cell Sorting (MACS) to Selection Spermatozoa in Patients with High Levels of Spermatic DNA Fragmentation

High Pregnancy and Implantation Rates Can Be Obtained Using Magnetic-Activated Cell Sorting (MACS) to Selection Spermatozoa in Patients with High Levels of Spermatic DNA Fragmentation

Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa

Diagnostic tools in male infertility—the question of sperm dysfunction

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