PDF(Pubmed)
Abstract：
The global fall in male fertility is a complicated process driven by a variety of factors, including environmental exposure, lifestyle, obesity, stress, and aging. The availability of assisted reproductive technology (ART) has allowed older couples to conceive, increasing the average paternal age at first childbirth. Advanced paternal age (APA), most often considered male age ≥40, has been described to impact several aspects of male reproductive physiology. In this prospective cohort study including 200 normozoospermic patients, 105 of whom were ≤35 years (non-APA), and 95 of whom were ≥42 years (APA), we assessed the impact of paternal age on different endpoints representative of sperm quality and cryopreservation tolerance. Non-APA patients had superior fresh semen quality; DNA fragmentation was notably increased in APA as compared to non-APA individuals (21.7% vs. 15.4%). Cryopreservation further increased the DNA fragmentation index in APA (26.7%) but not in non-APA patients. Additionally, APA was associated with increased mtDNAcn in both fresh and frozen/thawed sperm, which is indicative of poorer mitochondrial quality. Cryopreservation negatively impacted acrosome integrity in both age groups, as indicated by reduced incidences of unreacted acrosome in relation to fresh counterparts in non-APA (from 71.5% to 57.7%) and APA patients (from 75% to 63%). Finally, cryopreservation significantly reduced the phosphorylation status of proteins containing tyrosine residues in sperm from young males. Therefore, the present findings shed light on the effects of paternal age and cryopreservation on sperm quality and serve as valuable new parameters to improve our understanding of the mechanisms underlying sperm developmental competence that are under threat in current ART practice.
摘要：
全球男性生育率下降是一个由多种因素驱动的复杂过程，包括环境暴露，生活方式,肥胖，压力，和衰老。辅助生殖技术（ART）的可用性使年长的夫妇能够怀孕，增加第一次分娩时的平均父亲年龄。高级父亲年龄（APA），大多数人认为男性年龄≥40岁，已被描述为影响男性生殖生理的几个方面。在这项包括200名正常精子症患者的前瞻性队列研究中，其中105岁≤35岁(非APA)，其中95人≥42岁(APA)，我们评估了父亲年龄对代表精子质量和冷冻保存耐受性的不同终点的影响.非APA患者的新鲜精液质量较好；与非APA个体相比，APA的DNA片段显着增加（21.7％vs.15.4%）。冷冻保存进一步增加了APA（26.7％）的DNA片段化指数，而非APA患者则没有。此外,APA与新鲜和冷冻/解冻精子中mtDNAcn的增加有关，这表明线粒体质量较差。冷冻保存对两个年龄组的顶体完整性都有负面影响，在非APA患者（从71.5%到57.7%）和APA患者（从75%到63%）中，未反应的顶体发生率与新鲜对应物相比有所降低。最后,冷冻保存显着降低了年轻男性精子中含有酪氨酸残基的蛋白质的磷酸化状态。因此,本研究结果揭示了父代年龄和冷冻保存对精子质量的影响,并作为有价值的新参数,可提高我们对当前ART实践中受到威胁的精子发育能力的潜在机制的理解.
