Rey Juan Carlos University, Madrid, Spain; IVI-RMA Madrid, Spain.
IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Valencia, Spain.
Reprod Biomed Online. 2022 Jun;44(6):1090-1100. doi: 10.1016/j.rbmo.2021.10.010. Epub 2021 Oct 25.
How do age and normo- or oligoasthenozoospermia affect telomere length dynamics in spermatozoa and blood?
Sperm and blood samples were collected from a cohort of 37 men aged 25 and under and 40 men aged 40 and over, with either normozoospermia (NZ) or oligoasthenozoospermia (OAZ). Telomere length was evaluated using quantitative fluorescence in-situ hybridization. Telomerase mRNA (TERC and TERT) and shelterin (TRF1) gene expression were analysed using quantitative real-time polymerase chain reaction. TRF1 protein immunoreactivity was also evaluated using immunofluorescence.
Mean sperm telomere length (STL) increased with age in the NZ group; older NZ men accumulated the longest telomeres (P < 0.001). In peripheral blood mononuclear cells (PBMC), mean telomere length decreased with age in NZ groups, although not reaching statistical significance. Interestingly, the younger OAZ group had the shortest mean telomere length (versus young NZ, P = 0.0081; versus old NZ, P = 0.0116; versus old OAZ, P = 0.0009) and accumulated the highest percentage of short telomeres compared with the other groups (overall P = 0.0017). Analysis of TERC and TERT mRNA expression in spermatozoa and PBMC did not show significant differences among groups. Statistically significant positive correlations were found between STL and seminal parameters in younger NZ men (P = 0.009 for sperm count and P = 0.007 for total progressive motility). Protein immunoreactivity of TRF1 in blood was not significantly different in all groups analysed.
The OAZ group did not show the increase of STL with age that is seen in NZ individuals, suggesting that telomere length elongation mechanisms fail in OAZ patients. In PBMC, younger OAZ individuals showed significantly shorter mean telomere length, suggesting that this parameter could be a good biomarker of OAZ in younger OAZ patients. Telomerase gene and TRF1 mRNA expression and TRF1 protein immunoreactivity did not differ significantly between groups, and so these factors cannot be used as OAZ biomarkers.
年龄和正常或轻度少精子症如何影响精子和血液中的端粒长度动态?
从年龄在 25 岁及以下的 37 名男性和年龄在 40 岁及以上的 40 名男性中采集精子和血液样本,这些男性要么是正常精子症(NZ),要么是轻度少精子症(OAZ)。使用定量荧光原位杂交评估端粒长度。使用定量实时聚合酶链反应分析端粒酶 mRNA(TERC 和 TERT)和庇护素(TRF1)基因表达。还使用免疫荧光法评估 TRF1 蛋白免疫反应性。
NZ 组中,精子端粒长度(STL)随年龄增长而增加;年龄较大的 NZ 男性积累的端粒最长(P<0.001)。在 NZ 组的外周血单核细胞(PBMC)中,端粒长度随年龄增长而减少,但无统计学意义。有趣的是,较年轻的 OAZ 组具有最短的平均端粒长度(与年轻的 NZ 相比,P=0.0081;与年长的 NZ 相比,P=0.0116;与年长的 OAZ 相比,P=0.0009),与其他组相比,积累了最高比例的短端粒(总 P=0.0017)。精子和 PBMC 中 TERC 和 TERT mRNA 表达的分析并未显示组间有显著差异。在较年轻的 NZ 男性中,STL 与精液参数呈显著正相关(精子计数 P=0.009,总前向运动精子活力 P=0.007)。分析的所有组中,血液中 TRF1 蛋白免疫反应性无显著差异。
OAZ 组未出现 NZ 个体中所见的端粒长度随年龄增长而增加的情况,表明 OAZ 患者的端粒延长机制失败。在 PBMC 中,较年轻的 OAZ 个体的平均端粒长度明显缩短,这表明该参数可能是年轻 OAZ 患者 OAZ 的良好生物标志物。端粒酶基因和 TRF1 mRNA 表达以及 TRF1 蛋白免疫反应性在组间无显著差异,因此这些因素不能作为 OAZ 的生物标志物。