Oxidative DNA damage in human sperm influences time to pregnancy

Loft, Steffen; Jensen, Tina Kold; Hjøllund, Niels Henrik; Giwercman, Aleksander; Gyllemborg, Jesper; Ernst, Erik; Olsen, Jørn; Scheike, Thomas H.; Poulsen, Henrik E.; Bonde, Jens Peter

doi:10.1093/humrep/deg202

Cited by 174 publications

(117 citation statements)

References 38 publications

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“…Studies have shown that sperm DNA damage is associated with a prolonged time to pregnancy and a very low probability of achieving a natural pregnancy [Evenson et al 1999;Giwercman et al 2010;Loft et al 2003;Spano et al 2000]. A systematic review and meta-analysis of published natural pregnancy studies clearly correlates sperm DNA damage and failure to achieve a natural pregnancy (odds ratio (OR) = 7.01, 95% CI 3.68, 13.36, p < 0.001; Table 1).…”

Section: Relationship Between Sperm Dna Damage and Pregnancymentioning

confidence: 97%

Are sperm chromatin and DNA defects relevant in the clinic?

Zini

2011

Systems Biology in Reproductive Medicine

227

196

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There has been an increase in the use of sperm DNA and chromatin integrity tests in the evaluation of the infertile man with the hypothesis that these tests may better diagnose infertility and predict reproductive outcomes. This review discusses the etiology of sperm DNA damage, briefly describing the tests of sperm DNA damage, and evaluates the relationship between sperm DNA damage and reproductive outcomes. A systematic review of the literature allows us to conclude that sperm DNA damage is associated with lower natural, intra-uterine insemination (IUI), and in vitro fertilization (IVF) pregnancy rates. Studies to date have not shown a clear association between sperm DNA and chromatin defects and pregnancy outcomes after intra-cytoplasmic sperm injection (ICSI). However, we cannot exclude the possibility that very high levels of DNA damage will impact on ICSI outcomes. In couples undergoing IVF or ICSI, there is evidence to show that sperm DNA damage is associated with an increased risk of pregnancy loss. A limitation of this systematic review and meta-analysis is that it does not address the heterogeneity of the individual study characteristics. Although the clinical utility of tests of sperm DNA damage remains to be firmly established, the data suggest that there is clinical value in testing couples prior to assisted reproductive technologies (ARTs IUI, IVF, and ICSI) and in those couples with recurrent miscarriages. Additional, well-designed prospective studies are needed before testing becomes a routine part of patient care.

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Section: Relationship Between Sperm Dna Damage and Pregnancymentioning

confidence: 97%

Are sperm chromatin and DNA defects relevant in the clinic?

Zini

2011

Systems Biology in Reproductive Medicine

227

196

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“…Although sperm are highly differentiated cells with a characteristic morphology that render their DNA compact and protected from surrounding toxic substances [4], sperm DNA can be damaged through three major mechanisms: (i) oxidative stress -the main cause of sperm DNA fragmentation in mature sperm [5], (ii) alterations in chromatin packing [6], and (iii) abortive apoptosis [7]. About 10 % of fertile men and 20-25 % of infertile men present high levels of sperm DNA damage [8], which is associated with reduced reproductive potential [9][10][11][12] and embryo quality [13] and elevated miscarriage rates [14]. Moreover, it increases the risk of iatrogenic transmission of genetic defects during assisted reproduction techniques (ART) [15].…”

Section: Introductionmentioning

confidence: 99%

Unraveling the sperm proteome and post-genomic pathways associated with sperm nuclear DNA fragmentation

Intasqui

Camargo

Giudice

et al. 2013

J Assist Reprod Genet

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Purpose Sperm DNA fragmentation has been suggested as a marker for infertility diagnosis and prognosis. Hence, understanding its impact on male physiology and post-genomic pathways would be clinically important. We performed the proteomics and functional enrichment analyses of viable spermatozoa from ejaculates with low and high sperm DNA fragmentation to identify protein expression and pathways altered in association with sperm DNA fragmentation. Methods Sperm DNA fragmentation using the Comet assay and the Komet 6.0.1 software was assessed in raw samples from 89 subjects from a human reproduction service. The Low and High sperm DNA fragmentation groups were formed according to the Olive Tail Moment variable. Spermatozoa proteins from these groups were pooled and analyzed by a shotgun proteomic approach (2D nanoUPLC-ESI-MS E ). Differentially expressed proteins were used for a functional enrichment study. Results Two hundred and fifty-seven proteins were identified or quantified in sperm from the Low and High sperm DNA fragmentation groups. Of these, seventy-one proteins were exclusively or overexpressed in the Low group, whereas twenty-three proteins were exclusively or overexpressed in the High group. One hundred and sixty-three proteins were conserved between these groups. We also functionally related the differentially expressed proteins in viable spermatozoa from the groups. Processes such as triacylglycerol metabolism, energy production, protein folding, response to unfolded proteins, and cellular detoxification were found to be altered in these cells. Conclusions Sperm DNA fragmentation is associated with differential protein expression in viable spermatozoa. These proteins may potentially be used as biomarkers for sperm DNA integrity.

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“…On the other hand, using donor oocytes (18-35 years old), no significant differences between DNA fragmentation and reproductive outcomes were found [34]. In contrast, an inverse relationship between sperm DNA oxidation (levels of 8-oxoDG) and monthly fecundity rate has been found in a naturally conceiving population where the average woman age was 25 [35], similarly to a donor conception cycle, while Esbert and colleagues [36] found that DNA damage in sperm was unrelated to fertilization, embryo morphology, and pregnancy rates in IVF or ICSI with own or donor oocytes.…”

Section: Relationship Between Ros and Reproductive Outcomesmentioning

confidence: 92%

Oxidative stress level in fresh ejaculate is not related to semen parameters or to pregnancy rates in cycles with donor oocytes

Pujol¹,

Obradors²,

Esteo³

et al. 2016

J Assist Reprod Genet

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Purpose The purpose of the present study is to study the relationship between oxidative stress (OS) in semen, semen characteristics, and reproductive outcomes in oocyte donation intracytoplasmic sperm injection (ICSI) cycles. Methods OS was measured in 132 semen samples. Results OS levels were as follows: very high (1.5 %), high (43.2 %), low (30.3 %), and very low (25.0 %). Overall seminal parameters were as follows: volume (ml) = 4.2 (SD 2.1), concentration (millions/ml) = 61.6 (SD 59.8), motility (a+ b%) = 47.4 (SD 18.0), and normal spermatozoa (%) = 8.2 (SD 5.1). Of the 101 cycles that reached embryo transfer, 55.4 % evolved in biochemical, 46.5 % in clinical, and 43.6 % in ongoing pregnancy. OS level does not relate to seminal parameters, fertilization rate, or pregnancy outcomes. Conclusions OS testing by nitro blue tetrazolium (NBT) in fresh ejaculate might not be useful for all patients. Reproductive results with young oocytes and ICSI do not seem to be affected by OS-level semen.

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Oxidative DNA damage in human sperm influences time to pregnancy

Abstract: The data suggest that oxidative damage to sperm DNA influences fecundity and the level of damage is relatively constant within an individual and not influenced by smoking.

Cited by 174 publications

References 38 publications

Are sperm chromatin and DNA defects relevant in the clinic?

Are sperm chromatin and DNA defects relevant in the clinic?

Unraveling the sperm proteome and post-genomic pathways associated with sperm nuclear DNA fragmentation

Oxidative stress level in fresh ejaculate is not related to semen parameters or to pregnancy rates in cycles with donor oocytes

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