Abstract

Sperm DNA fragmentation (sDF) negatively affects reproduction and is traditionally detected in total sperm population including viable and non-viable spermatozoa. Here, we aimed at exploring the ability of DNA fragmentation to discriminate fertile and subfertile men when detected in viable (viable sDF), non-viable (non-viable sDF), and total spermatozoa (total sDF). We revealed sDF in 91 male partners of infertile couples and 71 fertile men (max 1 year from natural conception) with LiveTUNEL coupled to flow cytometry, able to reveal simultaneously DNA fragmentation and cell viability. We found that the three sDF parameters discriminated fertile and subfertile men with similar accuracy and independently from age and basal semen parameters: AUCs (area under the curves) (95% CI) were: 0.696 (0.615–0.776), p < 0.001 for total sDF; 0.718 (0.640–0.797), p < 0.001 for viable sDF; 0.760 (0.685–0.835), p < 0.001 for non-viable sDF. We also found that total and non-viable but not viable sDF significantly correlated to age and semen quality. In conclusion, the three sDF parameters similarly discriminated fertile and subfertile men. Viable spermatozoa with DNA fragmentation are likely cells able to fertilize the oocyte but failing to properly support subsequent embryo development. Non-viable sDF could be a sign of a subtler damage extended beyond the non-viable cells.

Highlights

  • Male infertility affects 7% of men and in up to 40% of cases, the causes of such a condition is not fully understood

  • We demonstrated that sperm DNA fragmentation (sDF) in a sperm subpopulation containing viable DNA fragmented spermatozoa was more predictive of the male fertility status than sDF detected in the whole sperm population [10]

  • Since we were interested in comparing the new sDF parameters to sDF as determined by traditional TUNEL, total sDF was calculated by gating total spermatozoa without discriminating viable and non-viable spermatozoa (Figure 1C)

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Summary

Introduction

Male infertility affects 7% of men and in up to 40% of cases, the causes of such a condition is not fully understood. In Western societies a progressive deterioration of spermatogenesis occurred in the last four decades [1] along with an increased incidence of other pathologies of the male reproductive system [2]. It is believed that changes in lifestyle and the increasing exposure to environmental pollution have a great role in the deterioration of semen quality and in the increase of male infertility occurred in the last forty years [3,4,5]. Among the alterations provoked by noxious lifestyle factors and by pollution on male fertility, sperm DNA fragmentation (sDF) plays an important role [6]. The literature on these topics is controversial and we are far from understanding how best to introduce the assessment of sDF into the male infertility work-up [14]

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