Sperm DNA Integrity Assessment: A New Tool in Diagnosis and Treatment of Fertility

Infertility affects 15% of all couples. Although male infertility factors with reduced semen quality are contributing to about half of all involuntary childlessness, the value of standard semen parameters in prediction of fertilityin vivoand choice of proper method for assisted reproduction is limited. In the search for better markers of male fertility, during the last 10 years, assessment of sperm DNA integrity has emerged as a strong new biomarker of semen quality that may have the potential to discriminate between infertile and fertile men. Sperm DNA Fragmentation Index (DFI) as assessed by the flow cytometric Sperm Chromatin Structure Assay (SCSA) can be used for evaluation of sperm chromatin integrity. The biological background for abnormal DFI is not completely known, but clinical data show that DFI above 30% is associated with very low chance for achieving pregnancy in natural way or by insemination, but notin vitro. Already when the DFI is above 20%, the chance of natural pregnancy may be reduced, despite other sperm parameters being normal. Thus this method may explain a significant proportion of cases of unexplained infertility and can be beneficial in counselling involuntary childless couples need ofin vitrofertilisation.

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Are semen quality parameters sufficient for biomonitoring spermatozoa DNA integrity and oxidatively damaged DNA

Biomonitoring ◽

10.1515/bimo-2015-0004 ◽

2015 ◽

Vol 2 (1) ◽

Author(s):

Hueiwang Anna Jeng ◽

Ruei-Nian Li ◽

Wen-Yi Lin

Keyword(s):

Dna Damage ◽

Dna Fragmentation ◽

Semen Quality ◽

Quality Parameters ◽

Semen Parameters ◽

Sperm Chromatin ◽

Dna Integrity ◽

Phase System ◽

Sperm Dna Fragmentation ◽

Sperm Dna

Abstract:The present study aimed to investigate the relationship between semen quality parameters and DNA integrity, and determine whether semen quality parameters could serve as a reliable biomarker for monitoring sperm DNA damage. Conventional semen parameters from a total of 202 male human subjects were analyzed. DNA fragmentation and 8-oxo-7,8-dihydro-2′- deoxyguanosine (8-oxoGuo) were used to assess sperm DNA integrity. DNA fragmentation was analyzed by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and sperm chromatin structure assay (SCSA), while 8-oxodGuo was quantified by the liquid chromatography/tandem mass spectrometry (LC-MS/MS) coupled with an on-line solid phase system. The levels of 8-oxodGuo levels in sperm were related to the percentages of DNA fragmentation measured by both the TUNEL and SCSA (r = 0.22, p = 0.048; r = 0.12, p = 0.039). Sperm vitality, motility and morphology from all of the participants exhibited a weak correlation with the levels of 8-oxodGuo and the percentages of DNA fragmentation. Semen quality parameters may be independent of the formation of DNA fragmentation and oxidative adducts in sperm. Semen quality parameters may be insufficient to monitor sperm DNA fragmentation and oxidative damage. DNA damage in sperm is recommended to be included in routine measurements.

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Influence of bovine sperm DNA fragmentation and oxidative stress on early embryo in vitro development outcome

Reproduction ◽

10.1530/rep-13-0123 ◽

2013 ◽

Vol 146 (5) ◽

pp. 433-441 ◽

Cited By ~ 48

Author(s):

Renata Simões ◽

Weber Beringui Feitosa ◽

Adriano Felipe Perez Siqueira ◽

Marcilio Nichi ◽

Fabíola Freitas Paula-Lopes ◽

...

Keyword(s):

Oxidative Stress ◽

Dna Fragmentation ◽

Sperm Chromatin ◽

Dna Integrity ◽

Sperm Dna Fragmentation ◽

Cleavage Rate ◽

Sperm Dna Integrity ◽

Sperm Dna ◽

Significant Difference

Sperm chromatin fragmentation may be caused by a number of factors, the most significant of which is reactive oxygen species. However, little is known about the effect of sperm oxidative stress (OS) on DNA integrity, fertilization, and embryonic development in cattle. Therefore, the goal of this study was to evaluate the influence of sperm OS susceptibility on the DNA fragmentation rate and in vitro embryo production (IVP) in a population of bulls. Groups of cryopreserved sperm samples were divided into four groups, based on their susceptibility to OS (G1, low OS; G2, average OS; G3, high OS; and G4, highest OS). Our results demonstrated that the sperm DNA integrity was compromised in response to increased OS susceptibility. Furthermore, semen samples with lower susceptibility to OS were also less susceptible to DNA damage (G1, 4.06%; G2, 6.09%; G3, 6.19%; and G4, 6.20%). In addition, embryo IVP provided evidence that the embryo cleavage rate decreased as the OS increased (G1, 70.18%; G2, 62.24%; G3, 55.85%; and G4, 50.93%), but no significant difference in the blastocyst rate or the number of blastomeres was observed among the groups. The groups with greater sensitivity to OS were also associated with a greater percentage of apoptotic cells (G1, 2.6%; G2, 2.76%; G3, 5.59%; and G4, 4.49%). In conclusion, we demonstrated that an increased susceptibility to OS compromises sperm DNA integrity and consequently reduces embryo quality.

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Sperm DNA fragmentation: causes and identification

Zygote ◽

10.1017/s0967199419000595 ◽

2019 ◽

Vol 28 (1) ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Thais Rose dos Santos Hamilton ◽

Mayra Elena Ortiz D’Ávila Assumpção

Keyword(s):

Dna Fragmentation ◽

Semen Analysis ◽

Sperm Chromatin ◽

Dna Integrity ◽

Sperm Dna Fragmentation ◽

Functional Capability ◽

Sperm Dna Integrity ◽

Sperm Dna ◽

Fertility Disorders ◽

Chromatin Integrity

SummarySperm DNA fragmentation is referred to as one of the main causes of male infertility. Failures in the protamination process, apoptosis and action of reactive oxygen species (ROS) are considered the most important causes of DNA fragmentation. Action of ROS or changes in sperm protamination would increase the susceptibility of sperm DNA to fragmentation. Routine semen analysis is unable to estimate sperm chromatin damage. Sperm DNA integrity influences sperm functional capability, therefore tests that measure sperm DNA fragmentation are important to assess fertility disorders. Actually, there is a considerable number of methods for assessing sperm DNA fragmentation and chromatin integrity, sperm chromatin stability assay (SCSA modified), sperm chromatin dispersion (SCD), comet assay, transferase dUTP nick end labelling (TUNEL); and protamine evaluation in sperm chromatin assay, such as toluidine blue, CMA3, protamine expression and evaluation of cysteine radicals. This review aims to describe the main causes of sperm DNA fragmentation and the tests commonly used to evaluate sperm DNA fragmentation.

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Effect of Alcohol Consumption on the Sperm DNA Integrity: A Systematic Review

Journal of Agricultural Science ◽

10.5539/jas.v9n13p136 ◽

2017 ◽

Vol 9 (13) ◽

pp. 136

Author(s):

Farah Hanan Fathihah Jaafar ◽

Khairul Osman ◽

Jaya Kumar ◽

Siti Fatimah Ibrahim

Keyword(s):

Dna Damage ◽

Alcohol Consumption ◽

Alcohol Withdrawal ◽

Semen Parameters ◽

Sperm Chromatin ◽

Dna Integrity ◽

Sperm Dna Damage ◽

Sperm Dna Integrity ◽

Sperm Dna ◽

Keywords Alcohol

There is no solid conclusion on the conventional sperm parameters in association with alcohol consumption, evaluation of sperm DNA integrity thus become a more reliable parameter. Hereby, this literature search was performed to summarize alcohol consumption on the sperm DNA integrity. A computerized database search was done through MEDLINE via Ovid (since 1946 until August 2017) and Cochrane was used. The following set of keywords: ‘alcohol consumption OR alcohol intake OR alcohol diet OR drinking alcohol OR ethanol diet’ AND ‘sperm DNA OR sperm chromatin OR sperm genome OR sperm histone OR sperm protamine’ were utilised. 24 articles were retrieved where only five studies conform to the inclusion criteria All studies demonstrated a negative effect of alcohol consumption on sperm DNA integrity, regardless of various range of alcohol doses and duration of alcohol consumption. Out of five studies reviewed, four studies were using a different approach to measure the sperm DNA damage. Hereby, this review identified a need to use a single approach of DNA damage test by having various method of alcohol administration and/or vice versa so that the extension of sperm DNA damage to alcohol consumption will have a better conclusion. On the same note, a few studies have reported the reversibility on conventional semen parameters, none has been done on the sperm DNA damage upon alcohol withdrawal. Therefore, the role of alcohol withdrawal on the reversibility of sperm DNA damage needs to be as well investigated further.

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Effect of in vitro exposure to lead chloride on semen quality and sperm DNA fragmentation

Zygote ◽

10.1017/s0967199413000671 ◽

2014 ◽

Vol 23 (3) ◽

pp. 384-393 ◽

Cited By ~ 9

Author(s):

M. Gomes ◽

A. Gonçalves ◽

E. Rocha ◽

R. Sá ◽

A. Alves ◽

...

Keyword(s):

Dna Fragmentation ◽

Room Temperature ◽

Semen Quality ◽

Lead Chloride ◽

Dna Integrity ◽

Sperm Dna Fragmentation ◽

Progressive Motility ◽

Sperm Dna ◽

In Vitro Exposure

SummaryExposure to lead may cause changes in the male reproductive system. We evaluated the effect of lead chloride (PbCl2) in vitro on semen quality from 31 individuals. Samples were incubated at room temperature for two exposure times (4 h and 8 h) and with two concentrations of PbCl2 (15 μg/ml or 30 μg/ml). Results showed that PbCl2 significantly inhibited rapid progressive motility and caused an increase in the percentage of tail anomalies in both times and concentrations assessed, as well as a decrease in vitality in the group exposed to 30 μg/ml PbCl2. A significant increase in immotile sperm was also observed between the group control and the groups submitted to lead. Total motility and DNA fragmentation also showed a significant decrease and increase, respectively, after 4 h of incubation in the group exposed to 30 μg/ml and in both groups after 8 h of incubation. In conclusion, PbCl2 affected sperm parameters and DNA integrity, which are essential for male fertility.

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A cost for high levels of sperm competition in rodents: increased sperm DNA fragmentation

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2015.2708 ◽

2016 ◽

Vol 283 (1826) ◽

pp. 20152708 ◽

Cited By ~ 5

Author(s):

Javier delBarco-Trillo ◽

Olga García-Álvarez ◽

Ana Josefa Soler ◽

Maximiliano Tourmente ◽

José Julián Garde ◽

...

Keyword(s):

Dna Damage ◽

Sperm Competition ◽

Dna Fragmentation ◽

Sperm Chromatin ◽

Dna Integrity ◽

Sperm Dna Fragmentation ◽

Sperm Dna Damage ◽

Sperm Dna Integrity ◽

Sperm Dna ◽

Physical And Chemical

Sperm competition, a prevalent evolutionary process in which the spermatozoa of two or more males compete for the fertilization of the same ovum, leads to morphological and physiological adaptations, including increases in energetic metabolism that may serve to propel sperm faster but that may have negative effects on DNA integrity. Sperm DNA damage is associated with reduced rates of fertilization, embryo and fetal loss, offspring mortality, and mutations leading to genetic disease. We tested whether high levels of sperm competition affect sperm DNA integrity. We evaluated sperm DNA integrity in 18 species of rodents that differ in their levels of sperm competition using the sperm chromatin structure assay. DNA integrity was assessed upon sperm collection, in response to incubation under capacitating or non-capacitating conditions, and after exposure to physical and chemical stressors. Sperm DNA was very resistant to physical and chemical stressors, whereas incubation in non-capacitating and capacitating conditions resulted in only a small increase in sperm DNA damage. Importantly, levels of sperm competition were positively associated with sperm DNA fragmentation across rodent species. This is the first evidence showing that high levels of sperm competition lead to an important cost in the form of increased sperm DNA damage.

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Multiple Determinations of Sperm DNA Fragmentation Show That Varicocelectomy Is Not Indicated for Infertile Patients with Subclinical Varicocele

BioMed Research International ◽

10.1155/2014/181396 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 14

Author(s):

Agustín García-Peiró ◽

Jordi Ribas-Maynou ◽

María Oliver-Bonet ◽

Joaquima Navarro ◽

Miguel A. Checa ◽

...

Keyword(s):

Surgical Treatment ◽

Dna Fragmentation ◽

Semen Quality ◽

Sperm Quality ◽

Dna Integrity ◽

Sperm Dna Fragmentation ◽

Sperm Dna Integrity ◽

Sperm Dna ◽

Common Causes ◽

Infertile Patients

Varicocele is one of the most common causes of low semen quality, which is reflected in high percentages of sperm cells with fragmented DNA. While varicocelectomy is usually performed to ameliorate a patient’s fertility, its impact on sperm DNA integrity in the case of subclinical varicocele is poorly documented. In this study, multiple DNA fragmentation analyses (TUNEL, SCD, and SCSA) were performed on semen samples from sixty infertile patients with varicocele (15 clinical varicoceles, 19 clinical varicoceles after surgical treatment, 16 subclinical varicoceles, and 10 subclinical varicoceles after surgical treatment). TUNEL, SCD, and SCSA assays all showed substantial sperm DNA fragmentation levels that were comparable between subclinical and clinical varicocele patients. Importantly, varicocelectomy did improve sperm quality in patients with clinical varicocele; however, this was not the case in patients with subclinical varicocele. In summary, although infertile patients with clinical and subclinical varicocele have similar sperm DNA quality, varicocelectomy should only be advised for patients with clinical varicocele.

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Association Study of Sperm DNA Integrity, Routine Semen Parameters and In Vitro Fertilization Clinical Outcome

10.21203/rs.3.rs-549300/v1 ◽

2021 ◽

Author(s):

Yunzhu Lan ◽

Xinjian Feng ◽

Xingyu Sun ◽

Li Fu

Keyword(s):

In Vitro Fertilization ◽

Clinical Outcome ◽

Semen Parameters ◽

Dna Integrity ◽

Cleavage Rate ◽

Vitro Fertilization ◽

Progressive Motility ◽

Sperm Dna Integrity ◽

Sperm Dna

Abstract This paper explores the relationship among sperm DNA integrity, routine semen parameters and in vitro fertilization (IVF) clinical outcome. It applies sperm chromatin dispersion (SCD) test to conduct sperm DNA fragmentation index (DFI) towards the semen samples of 60 male patients who undergoing assisted reproduction techniques (ART) treatments including intrauterine insemination (IUI), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) treatment in human assisted reproductive medical technology of our hospital. According to the test results, semen samples are divided into group A (DFI≤10%), group B (10%<DFI<30%) and group C (DFI≥30%) to compare semen routine main parameters in each group as well as fertility rate, cleavage rate and high-quality embryonic rate. There is a negative correlation among DFI and sperm activate rate, progressive motility(PR) rate as well as non-progressive motility(NP) rate. The difference of the sperm activate rate, progressive motility rate and non-progressive motility rate in three groups are statistically significant (P<0.05), and there is no statistically significant difference in sperm concentration (P>0.05). The fertility rate, cleavage rate and high-quality embryonic rate in each group have no statistical significance (P>0.05). Sperm DNA integrity have some connection with routine semen parameters, thus, it could play a guiding role for the analysis of semen routine diagnosis. DFI has little influence on the assisted reproductive technology IVF clinical outcome, which requires follow-up tracking clinical outcome and a large number of samples for validation.

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