Jenkins Timothy G, Aston Kenneth I, Carrell Douglas T
Andrology and IVF Laboratories, Department of Surgery, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Transl Androl Urol. 2018 Jul;7(Suppl 3):S328-S335. doi: 10.21037/tau.2018.06.10.
Advanced paternal age has very real consequences in fertility, embryogenesis, and even offspring health. Specifically, advanced paternal age has been linked to delayed time to pregnancy and in some studies even appears to be linked to a decreased likelihood of achieving a pregnancy. Epidemiological and animal model evidence also suggests that the offspring of older fathers are at an elevated risk for neuropsychiatric disease. For these reasons it is essential that we have a comprehensive understanding of what actually occurs in the gametes of the aging male. Available data suggest that there are very clear patterns of aging in the sperm epigenome that can be directly detected in DNA methylation patterns. Importantly, these alterations are so consistent that a predictive model has been successfully generated to predict an individual's age based only on sperm DNA methylation signatures. Because this metric is the most direct way to detect aging in sperm, it is logical that these signatures may offer predictive value for the offspring abnormalities that are also correlated with advanced paternal age and as such may offer a unique opportunity to generate diagnostic tools that can identify personalized risks for each couple hoping to achieve a pregnancy. While a great deal of work still needs to be performed to understand the real diagnostic utility of sperm epigenetic marks, the potential is real and warrants further investigation particularly in the context of advanced paternal age.
父亲年龄过大对生育能力、胚胎发育乃至后代健康都有非常实际的影响。具体而言，父亲年龄过大与受孕时间延迟有关，在一些研究中甚至似乎与受孕可能性降低有关。流行病学和动物模型证据还表明，年长父亲的后代患神经精神疾病的风险更高。出于这些原因，我们必须全面了解衰老男性配子中实际发生的情况。现有数据表明，精子表观基因组存在非常明显的衰老模式，可直接在DNA甲基化模式中检测到。重要的是，这些改变非常一致，以至于已经成功生成了一个预测模型，仅根据精子DNA甲基化特征就能预测个体的年龄。由于这个指标是检测精子衰老的最直接方法，因此这些特征可能为同样与父亲年龄过大相关的后代异常提供预测价值，这是合乎逻辑的，因此可能提供一个独特的机会来生成诊断工具，为每对希望怀孕的夫妇识别个性化风险。虽然仍需要进行大量工作来了解精子表观遗传标记的实际诊断效用，但潜力是真实存在的，值得进一步研究，特别是在父亲年龄过大的背景下。
