Poor sperm quality and advancing age are associated with increased sperm DNA damage in infertile men

Varshini, J; Srinag, BS; Kalthur, Guruprasad; Krishnamurthy, Hanumanthappa; Kumar, Pratap; Rao, Satish; Adiga, Satish Kumar

doi:10.1111/j.1439-0272.2011.01243.x

Cited by 116 publications

(52 citation statements)

References 65 publications

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“…To date, the published data on the relationship between sperm DNA integrity and normal morphology are conflicting. Although some studies have shown that abnormal sperm morphology and DNA damage are related [20,61] other studies have not identified a significant relationship between these parameters [34,62]. Our data are convincing in view of the fact that the study involves a large cohort of infertile couples with very well defined sperm defects.…”

Section: Discussionsupporting

confidence: 58%

Which isolated sperm abnormality is most related to sperm DNA damage in men presenting for infertility evaluation

Belloc¹,

Benkhalifa²,

Cohen-Bacrie³

et al. 2014

J Assist Reprod Genet

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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.

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Section: Discussionsupporting

confidence: 58%

Which isolated sperm abnormality is most related to sperm DNA damage in men presenting for infertility evaluation

Belloc¹,

Benkhalifa²,

Cohen-Bacrie³

et al. 2014

J Assist Reprod Genet

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“…One paradigm that perfectly illustrates the power of these associations is paternal ageing. Thus, numerous studies demonstrate that paternal age is associated with a high incidence of DNA damage in human spermatozoa (Schmid et al, 2007;Singh et al, 2003;Varshini et al, 2012) as well as an increase in the mutational load subsequently carried by the offspring (Kong et al, 2012). Whether there is a mechanistic link between DNA damage in the germ line on the one hand and increased mutation rates in the embryo on the other is a critical issue that remains unresolved.…”

Section: Implications For Future Generations' Healthmentioning

confidence: 99%

The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment

Lewis

Aitken

Conner

et al. 2013

Reproductive BioMedicine Online

245

182

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Lewis, S.E.M. et al. (2013). The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment. Astract:Sperm DNA damage is a useful biomarker for male infertility diagnosis and prediction of assisted reproduction outcomes. It is associated with reduced fertilization rates, embryo quality and pregnancy rates, and higher rates of spontaneous miscarriage and childhood diseases. This review provides a synopsis of the most recent studies from each of the authors, all of whom have major track records in the field of sperm DNA damage in the clinical setting. It explores current laboratory tests and the accumulating body of knowledge concerning the relationship between sperm DNA damage and clinical outcomes. The paper proceeds to discuss the strengths, weaknesses and clinical applicability of current sperm DNA tests. Next, the biological significance of DNA damage in the male germ line is considered. Finally, as sperm DNA damage is often the result of oxidative stress in the male reproductive tract, the potential contribution of antioxidant therapy in the clinical management of this condition is discussed. DNA damage in human spermatozoa is an important attribute of semen quality. It should be part of the clinical work up and properly controlled trials addressing the effectiveness of antioxidant therapy should be undertaken as a matter of urgency. IntroductionMale factor infertility is implicated in more than 40% of couples presenting for assisted reproduction treatment. Conventional semen analysis continues to be the only routine test to diagnose this condition even though it is known that such descriptive assessments cannot discriminate between the spermatozoa of fertile and infertile men (Guzick et al., 2001). The shifting values for normality (all 'normal' values now lower) in the fifth edition of the WHO manual (World Health Organization, 2010) compared with the previous WHO editions may result in even less men being classified as infertile (Murray et al., 2012).

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“…Furthermore, it has been demonstrated that time to achieve pregnancy is also highly affected by male aging [25]. These evidences raise serious concerns regarding the adverse impacts of APA on the offspring, as it has been confirmed that sperm DNA damage is closely associated with APA [26,27]. Although a decrease in male fertility occurs with age, there is still the need to define an age threshold for which the risk of an adverse outcome due to APA is greater than the gain.…”

Section: Introductionmentioning

confidence: 99%

Aging of the Male Germline: Influence of Advanced Male Age on Reproductive Outcome

Rabaça¹,

Ferreira²

2016

Andrology(Los Angel)

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The rise in life expectancy and the desire to establish a stable career prior to parenthood leads couples to a delayed childbearing. Advanced parental age at the time of pregnancy portrays several risks, with the majority of couples above 35 experiencing reproductive impairments. While the effect of women's age on fertility is well known, the influence of paternal age is less understood. Thus, efforts have been made to comprehend the influence of APA on pregnancy upkeep and disease risk for the offspring. Over the last decades numerous studies aimed to establish the relationship between APA and male fertility potential. It has been found that APA is related to testicular and hormonal alterations, along with a decreased sperm production, quality and DNA integrity. As expected, these alterations compromise the reproductive potential of older men and have been associated with several fecundity problems, including increased time to pregnancy and abortion rates, and decreased fertilization and pregnancy rates. Additionally, alterations in offspring health, like genetic disorders, mental illnesses, congenital anomalies and cancer, have also been linked to APA. As a result, APA influence on the reproductive outcome must be taken into consideration when counseling couples attending family planning consultations or pursuing fertility treatments. Nonetheless, to date, there are still no definite results regarding this problem and an age threshold has yet not been established and additional research to better elucidate the effects of APA on fertility and offspring's health is needed. Likewise, establishing an age threshold for APA would be of great value to males thinking of delaying parenthood, and to physicians for medical advice purposes.

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Poor sperm quality and advancing age are associated with increased sperm DNA damage in infertile men

Cited by 116 publications

References 65 publications

Which isolated sperm abnormality is most related to sperm DNA damage in men presenting for infertility evaluation

Which isolated sperm abnormality is most related to sperm DNA damage in men presenting for infertility evaluation

The impact of sperm DNA damage in assisted conception and beyond: recent advances in diagnosis and treatment

Aging of the Male Germline: Influence of Advanced Male Age on Reproductive Outcome

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