Single and Double Strand Sperm DNA Damage: Different Reproductive Effects on Male Fertility

Abstract

Reproductive diseases have become a growing worldwide problem and male factor plays an important role in the reproductive diagnosis, prognosis and design of assisted reproductive treatments. Sperm cell holds the mission of carrying the paternal genetic complement to the oocyte in order to contribute to an euploid zygote with proper DNA integrity. Sperm DNA fragmentation had been used for decades as a male fertility test, however, its usefulness have arisen multiple debates, especially around Intracytoplasmic Sperm Injection (ICSI) treatments. In the recent years, it has been described that different types of sperm DNA breaks (single and double strand DNA breaks) cause different clinical reproductive effects. On one hand, single-strand DNA breaks are present extensively as a multiple break points in all regions of the genome, are related to oxidative stress and cause a lack of clinical pregnancy or an increase of the conception time. On the other hand, double-strand DNA breaks are mainly localized and attached to the sperm nuclear matrix as a very few break points, are possibly related to a lack of DNA repair in meiosis and cause a higher risk of miscarriage, low embryo quality and higher risk of implantation failure in ICSI cycles. The present work also reviews different studies that may contribute in the understanding of sperm chromatin as well as treatments to prevent sperm DNA damage.

DNA fragmentation of human spermatozoa: Simple assessment of single‐ and double‐strand DNA breaks and their respective dynamic behavioral response

“…It has been reported that massive SSBs can potentially decrease the probability of pregnancy or increase the time to achieve conception, whereas a relatively small number of DSBs presumably located at attachment sites to the sperm nuclear matrix can adversely influence embryo kinetics and implantation rate and increase the risk of recurrent miscarriage during the first trimester 54 . Nevertheless, this distinction between massive SSBs and DSBs in predicting reproductive outcome needs to be regarded with caution.…”

Sperm DNA Fragmentation: A New Guideline for Clinicians

“…In contrast, SSBs do not significantly impact embryo development or implantation rates [117]. Nonetheless, higher levels of SSBs are inversely related to the natural pregnancy outcome [118]. Thus, evaluation of SSB and DSB may provide important information during fertility evaluation of men [119].…”

Oxidative Stress in Male Infertility: Causes, Effects in Assisted Reproductive Techniques, and Protective Support of Antioxidants

“…Although it is difficult to establish which percentages of infertile patients have an underlying mechanism of oxidative stress, it is known that it could be present as a factor in asthenozoospermic, teratozospermic, and oligozoospermic patients who present reproductive issues [77,78]. All these parameters have been associated in different studies with a reduction in natural pregnancy, both in animal [79,80] and human studies [76,81,82], supporting the evidence that oxidative stress leads to a reduction in natural fertility rates [77,83].…”

“…In this context, however, it is worth mentioning that detecting these DNA breaks and its type heavily relies upon the sensitivity of the technique used to evaluate sperm DNA fragmentation (i.e., SCSA, SCDt, TUNEL, neutral Comet, alkaline Comet, etc. ), which leads to different correlations to clinical outcomes [76].…”