Sub-fertile sperm cells exemplify telomere dysfunction

The purpose of this study was to evaluate telomere homeostasis in sub-fertile compared to fertile human sperm. This observational, comparative study included 16 sub-fertile men who required intracytoplasmic sperm injection and 10 fertile men. At least 100 sperm cells from each participant were assessed. Main outcome measures were telomere length and telomere aggregates. Telomerase RNA component (TERC) copy number and telomere capture were assessed using fluorescence in situ hybridization technique and human telomerase reverse transcriptase (hTERT) using immunohistochemistry. Clinical backgrounds were similar. The percentage of sperm cells with shorter telomeres was higher among the sub-fertile compared to the fertile participants (3.3 +/- 3.1 vs. 0.6 +/- 1.2%, respectively; P < 0.005). The percentage of cells with telomere aggregates was significantly higher in the sub-fertile group (15.12 +/- 3.73 vs. 4.73 +/- 3.73%; P < 0.005). TERC gene copy number was similar between groups. The percentage of cells that were positive for hTERT was lower in the sub-fertile group (3.81 +/- 1.27 vs. 8.42 +/- 1.80%; P < 0.005). Telomere capture rates were higher among the sub-fertile sperm cells (P < 0.005). Sub-fertile sperm cells have short telomeres that are elongated by the alternative pathway of telomere capture. Dysfunctional telomeres may affect sperm fertilizability.