Andrology and IVF Laboratories, Department of Surgery, and Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA.
Adv Exp Med Biol. 2019;1166:47-56. doi: 10.1007/978-3-030-21664-1_3.
Compared to other cells, sperm undergo dramatic remodeling of their chromatin during late spermiogenesis in which approximately 95% of histones are removed and replaced with protamines. Despite this large-scale remodeling, key developmental genes, some miRNA genes, and imprinted genes retain their association with histone. The developmental genes have a unique epigenetic signature, termed bivalency, that poises the genes for embryonic activation. Anomalies in that epigenetic poising signature, either in the form of DNA methylation aberrations, improper protamination, or altered histone modifications, are associated with infertility and reduced embryogenesis capability. Additionally, some small noncoding RNAs are retained, while others are actively added to the sperm and appear to affect embryogenesis. Therefore, initial studies have begun to formulate pathways by which the sperm epigenome can be used as a diagnostic tool in the clinic. While in their infancy, these assays likely portend improved diagnostics and added information for patients and clinicians. Recent studies also highlight the possibility that the sperm epigenome can be used to evaluate lifestyle and environmental risks to the patient and potentially to the offspring.
与其他细胞相比，精子在晚期精子发生过程中经历了染色质的剧烈重塑，在此过程中，大约 95%的组蛋白被去除，并被鱼精蛋白取代。尽管发生了这种大规模的重塑，但关键的发育基因、一些 miRNA 基因和印记基因仍然与组蛋白结合。发育基因具有独特的表观遗传特征，称为二价性，使基因为胚胎激活做好准备。这种表观遗传平衡特征的异常，无论是 DNA 甲基化异常、不当的鱼精蛋白化还是组蛋白修饰改变，都与不孕和胚胎发育能力降低有关。此外，一些小的非编码 RNA 被保留下来，而另一些则被主动添加到精子中，并可能影响胚胎发生。因此，最初的研究已经开始制定途径，通过这些途径，精子表观基因组可以作为临床诊断工具。虽然这些检测方法还处于起步阶段，但它们可能预示着诊断的改善，并为患者和临床医生提供更多的信息。最近的研究还强调了精子表观基因组可用于评估患者和潜在后代的生活方式和环境风险的可能性。
