De novo cytogenetic alterations in spermatozoa of subfertile males might be due to genome instability associated with idiopathic male infertility: Experimental evidences and Review of the literature
Running title: Sperm cytogenetic alterations and male infertility (original) (raw)
Related papers
Impact of DNA damage on the frequency of sperm chromosomal aneuploidy in normal and subfertile men
Iranian biomedical journal, 2011
Various frequencies of sperm aneuploidy are reported in sperms of subfertile patients compared to normal individuals. Moreover, sperm DNA damage is shown to be associated with male infertility. In this study, the rate of DNA damage and frequencies of aneuploidy in sperms of subfertile patients was investigated. Semen samples were obtained from healthy normal and subfertile (oligozoospermia, asthenozoospermia, and oligoasthenozoospermia) men. The frequency of aneuploidy was assessed using primed in situ labeling (PRINS) analysis with specific primers for chromosomes 18, 21, X, and Y. Sperm DNA damage was assessed using alkaline comet assay. The mean frequencies of disomy for the patients were significantly higher than normal for all chromosomes (P < 0.01). The extent of DNA damage in sperms of subfertiles was significantly higher than in normal individuals (P < 0.001). The obtained results indicated that higher rate of DNA damages led to higher frequency of chromosomal disomy e...
The etiologies of sperm DNA abnormalities in male infertility: An assessment and review
International Journal of Reproductive BioMedicine
The sperm DNA damage may occur in testis, genital ducts, and also after ejaculation. Mechanisms altering chromatin remodeling are abortive apoptosis and oxidative stress resulting from reactive oxygen species. Three classifications of intratesticular, post-testicular, and external factors have been correlated with increased levels of sperm DNA damage which can affect the potential of fertility. Alcohol consumption may not increase the rate of sperm residual histones and protamine deficiency; however, it causes an increase in the percentage of spermatozoa with DNA fragmentation and apoptosis. In a medical problem as spinal cord injury, poor semen parameters and sperm DNA damage were reported. Infection induces reactive oxygen species production, decreases the total antioxidant capacity and sperm DNA fragmentation or antigen production that lead to sperm dysfunctions and DNA fragmentation. While reactive oxygen species generation increases with age, oxidative stress may be responsible for the age-dependent sperm DNA damage. The exposing of reproductive organs in older men to oxidative stress for a long time may produce more DNA-damaged spermatozoa than youngers. Examining the sperm chromatin quality in testicular cancer and Hodgkin's lymphoma patients prior to chemotherapy demonstrated the high incidence of DNA damage and low compaction in spermatozoa at the time of diagnosis. In chemotherapy cycles with genotoxic agents in cancer patients, an increase in sperm DNA damage was shown after treatment. In overall, those factors occurring during the prenatal or the adult life alter the distribution of proteins associated with sperm chromatin induce changes in germ cells which can be detected in infertile patients.
The etiologies of DNA abnormalities in male infertility: An assessment and review
International journal of reproductive biomedicine (Yazd, Iran), 2017
The sperm DNA damage may occur in testis, genital ducts, and also after ejaculation. Mechanisms altering chromatin remodeling are abortive apoptosis and oxidative stress resulting from reactive oxygen species. Three classifications of intratesticular, post-testicular, and external factors have been correlated with increased levels of human sperm DNA damage which can affect the potential of fertility. Lifestyle, environment, medical, and iatrogenic factors might be considered to cause dysmetabolism to make distracting interactions and endocrine disrupting compounds. As a result, these may induce chromatin/DNA alteration in germ cells, which may be transmitted across generations with phenotypic consequencesAlcohol consumption may not increase the rate of sperm residual histones and protamine deficiency; however, it causes an increase in the percentage of spermatozoa with DNA fragmentation and apoptosisIn a medical problem as spinal cord injury, poor semen parameters and sperm DNA dama...
Increased sperm nuclear DNA damage in normozoospermic infertile men: a prospective study
Fertility and Sterility, 2002
Objective: To evaluate levels of sperm nuclear DNA damage in infertile men with normal and abnormal standard semen parameters. Design: Prospective study. Setting: Male infertility clinic. Patient(s): Ninety-two men seeking infertility treatment and 16 fertile volunteers. Intervention(s): Standard semen analysis was performed according to the World Health Organization guidelines. Main Outcome Measure(s): Sperm DNA damage was assessed by sperm chromatin structure assay and the results expressed as %DFI. Result(s): Of the 92 patients, 21 (23%) had normal standard sperm parameters (concentration, motility, and normal sperm forms), while 71 (77%) had an abnormality in one or more of these parameters. The %DFI [median (25th and 75th percentiles)] in infertile men with normal sperm parameters [23 (15, 32)] was significantly higher than fertile donors [15 (11, 20)] (Pϭ.02), but not significantly different from infertile men with abnormal sperm parameters [28 (18, 41)] (Pϭ.27).
The higher risk for sperm DNA damage in infertile men
Ginekologia Polska, 2019
Objectives: Supplementary assays are needed for determination of relationships between sperm biomarkers and fertility potential. Therefore, our research was designed to determine the extent of sperm DNA fragmentation (SDF) and establish a discriminating threshold of SDF for fertility potential. Material and methods: Semen characteristics were evaluated according to World Health Organization recommendations, and SDF was assessed by sperm chromatin dispersion test on ejaculated spermatozoa from infertile and healthy normozoospermic men. Results: A higher proportion of SDF was noted in infertile men (median 23.00%) than normozoospermic (median 14.00%). Significantly less subjects (17.03%) with low SDF level (≤ 15%) and more (35.17%) with high SDF level (> 30%) were found for the infertile group vs the normooospermic (57.90% and 5.26%, respectively). Infertile group had significantly lower odds ratio (OR) for having a low SDF level (OR: 0.1493) and higher OR for having a high SDF level (OR: 9.7627). Receiver operating characteristic analysis [area under curve (AUC) = 0.785] revealed that 20% SDF is predictive value for discriminating between infertile and normozoospermic subjects. SDF was negatively correlated with the sperm number, morphology, progressive motility and vitality but positively with the teratozoospermia index. Conclusions: Our study demonstrates: (1) a significant difference in the extent of SDF and in the risk for having damaged sperm DNA between infertile and normozoospermic men, (2) > 20% SDF has negative predictive value for fertility potential, (3) coexistence of abnormal standard sperm parameters with sperm chromatin damages. Therefore, SDF should be considered as a highly valuable indicator of male fertility potential.
Journal of Assisted Reproduction and Genetics, 2014
Background Sperm DNA damage is common in infertile men and is associated with poor semen parameters but the impact of an isolated sperm abnormality on sperm DNA damage has not been studied. Objective To evaluate sperm DNA damage in a large cohort of infertile men with isolated sperm defects. Design, setting and participants Retrospective study of 1084 consecutive, non-azoospermic infertile men with an isolated sperm defect: isolated oligozoospermia (iOligo), isolated asthenozoospermia (iAstheno) or isolated teratozoospermia (iTerato). Outcome measurements and statistical analysis We examined and compared clinical parameters, conventional semen parameters and %sperm DNA fragmentation (%SDF, assessed by flow cytometry-based Terminal deoxynucleotidyl transferase-mediated dUTP Nick End-Labeling assay) in the three groups of men. Results and limitations The mean (±SD) %SDF was significantly higher in the iAstheno compared to the iOligo and iTerato groups (25.0±14.0 vs. 19.2±11.6 and 20.7±12.1 %, respectively, P<0.0001). Similarly, the proportion of men with high %SDF (>30 %) was significantly higher in the iAstheno compared to the iOligo and iTerato groups (31 % vs. 18 % and 19 %, respectively, P<0.0001). In the group of 713 men with iAstheno, %SDF was positively correlated with paternal age (r=0.20, P<0.0001) and inversely correlated with %progressive motility (r=−0.18, P<0.0001). In the subset of 218 men with iTerato, %SDF was also positively correlated with paternal age (r=0.15, P=0.018) and inversely correlated with %progressive motility (r=−0.26, P=0.0001). Conclusions In this large cohort of infertile men with isolated sperm abnormalities, we have found that the sperm DNA fragmentation level is highest in the men with sperm motility defects and that 31 % of these men have high levels of sperm DNA fragmentation. The data indicate that poor motility is the sperm parameter abnormality most closely related to sperm DNA damage.
Molecular Reproduction and Development, 2012
Male infertility is a multi-factorial disorder, and identification of its etiology in an individual is critical for treatment. Systematically elucidating the underlying genetic causes (chromosomal and Yq microdeletion) and factors, such as reactive oxygen species (ROS) levels and total antioxidant capacity (TAC), which contribute to sperm DNA damage, may help to reduce the number of men with idiopathic infertility and provide them with the most suitable therapeutics and counseling. This study was done to comprehensively investigate genetic and oxidative stress factors that might be the etiology of a large percentage of men with idiopathic infertility. One hundred twelve infertile men and 76 fertile controls were screened for chromosomal aberrations and Yq microdeletions. ROS, TAC, and sperm DNA damage were assessed in cytogenetically normal, non-azoospermic men with intact Y chromosome (n ¼ 93). ROS was assessed in neat and washed semen by chemiluminescence; seminal TAC with a commercially available kit; and sperm DNA damage by the comet assay. Two men had cytogenetic abnormalities and seven men harbored Yq microdeletions. ROS levels in neat and washed semen of infertile men were significantly higher (P < 0.01) than controls. Infertile men had significantly lower (P < 0.01) TAC levels (1.79 mM), whereas sperm DNA fragmentation in infertile men was significantly higher (P < 0.01) than controls. Genetic factors and oxidative stress cumulatively account for large number of idiopathic infertile cases. Unlike, genetic causes, which cannot be cured, timely identification and management of oxidative stress may help to reverse/reduce the effects on induced DNA damage, and improve the outcomes for infertile males.
Fertility and Sterility, 2001
To evaluate two different assays of human sperm DNA integrity, DNA denaturation (DD) and DNA fragmentation (DF), and to correlate these with standard semen parameters. Design: Prospective, observational study. Setting: University infertility clinic. Patient(s): Forty consecutive semen samples from 33 nonazoospermic men presenting for infertility evaluation and 7 fertile men presenting for vasectomy. Intervention(s): Assessment of sperm concentration, motility, morphology, DD and DF. Main Outcome Measure(s): Sperm DD and DF in fertile and infertile men.
Etiologies of sperm DNA damage and its impact on male infertility
Andrologia, 2020
Infertility is defined as the inability to conceive after 12 months of regular, unprotected intercourse (Sabanegh & Agarwal, 2010). Although 60%-75% of couples conceive within 6 months, and 90% within 12 months (Spira, 1986), approximately 48.5 million couples worldwide are considered infertile within this definition (Agarwal et al., 2019; Sharlip et al., 2002). Male factor infertility affects up to 50% of couple infertility and is solely responsible for 20% of overall infertility (Thonneau et al., 1991). In recent decades, the incidence of male factor infertility has increased (Turner et al., 2020; Zandieh et al., 2018). Semen analysis is considered as the cornerstone of the male fertility evaluation. This analysis provides information into the possible extent and severity of infertility problems, and aids in diagnosis and clinical management. Based on several population studies, the World Health Organization (WHO) provided updated sampling and laboratory guidelines with clinical thresholds to evaluate male reproductive potential through semen analysis (Mayorga-Torres, Camargo, Cadavid, du Plessis, & Cardona Maya, 2017). However, there remain several limitations associated with the conventional semen analysis in the assessment of male infertility (Majzoub, Agarwal, & Esteves, 2019). These limitations have led to the development of advanced sperm function and seminal fluid quality assessments, such as oxidative stress and sperm DNA fragmentation (SDF), that may better guide diagnostics, management and the prediction of male fertility outcomes (Esteves, Sharma, Gosálvez, & Agarwal, 2014). Spermatozoa are highly differentiated cells, which are made up of a head, mid piece and tail. The head of the spermatozoa contains the haploid genome that is transmitted into the oocyte after successful fertilization. The integrity and composition of the sperm DNA is different from that of somatic cells and critical for its fusion with the maternal genome (Conwell, Vilfan, & Hud, 2003). Adequate sperm DNA integrity is critical for successful fertilization, embryo development, implantation and establishment of pregnancy as it contributes towards 50% of the embryonic genome (Baskaran et al., 2019; Braude, Bolton, & Moore, 1988). Sperm DNA integrity is therefore considered as an important marker of fertility potential of spermatozoa (Cho & Agarwal, 2018).