摘要
Purpose of ReviewPaternal metabolic disease before conception and during spermatogenesis can adversely impact the metabolic health of offspring in later life. Here, we review the current understanding of sperm epigenetic markers as contributors to intergenerational transmission of disease risk in both human and animal studies, and review potential intervention strategies.Recent FindingsEpidemiological studies suggest an increased risk of adverse outcomes in the offspring of fathers with obesity, diabetes, advanced age, smoking, and ancestral exposures. Potential molecular mechanisms contributing to intergenerational disease risk include genetics (DNA sequence) as well as epigenetic factors in the sperm, such as DNA methylation, chromatin and histone modification, and coding and noncoding RNAs. Potential strategies to interrupt intergenerational transmission of disease risk include increased physical activity, weight loss, bariatric surgery, cold exposure, and improved glycemic control prior to conception.SummaryMany studies suggest environmental factors experienced by fathers can program disease risk in the next generation via sperm cell–mediated transmission. Better understanding the mechanisms through which paternal metabolism influences sperm cells will help to design better intervention strategies. Future research will focus on the molecular signals that mediate the impact of paternal factors on sperm epigenetic signals and also how these affect offspring embryonic development and disease risk during adult life.
摘要译文
回顾目的在受孕前和精子发生过程中的父本代谢疾病可能对后代的后代代谢健康产生不利影响。在这里，我们回顾目前对精子表观遗传标记的理解，作为人类和动物研究中疾病风险代际传递的贡献者，并回顾潜在的干预策略。最近的研究结果流行病学研究表明，肥胖父亲后代的不良后果风险增加，糖尿病，高龄，吸烟和祖先暴露。导致代际疾病风险的潜在分子机制包括遗传学（DNA序列）以及精子中的表观遗传因子，例如DNA甲基化，染色质和组蛋白修饰，以及编码和非编码RNA。阻断疾病风险代际传播的潜在策略包括增加体力活动，减轻体重，减肥手术，冷暴露以及受孕前改善血糖控制。大量研究表明，父亲经历的环境因素可以通过精子细胞编制下一代的疾病风险介导的传输。更好地了解父系代谢影响精子细胞的机制将有助于设计更好的干预策略。未来的研究将集中在介导父系因子对精子表观遗传信号的影响的分子信号，以及这些信号如何影响成年后的胚胎发育和疾病风险。
Lei Su[1][2]]Mary Elizabeth Patti[1]]. Paternal Nongenetic Intergenerational Transmission of Metabolic Disease Risk[J]. Current Diabetes Reports, 2019,19(7)