Department of Veterinary Physiology & Pharmacology, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, Texas, USA.
Birth Defects Res. 2023 Nov 15;115(19):1825-1834. doi: 10.1002/bdr2.2215. Epub 2023 Jul 9.
Until recently, clinicians and researchers did not realize paternal exposures could impact child developmental outcomes. Indeed, although there is growing recognition that sperm carry a large amount of non-genomic information and that paternal stressors influence the health of the next generation, toxicologists are only now beginning to explore the role paternal exposures have in dysgenesis and the incidence of congenital malformations. In this commentary, I will briefly summarize the few studies describing congenital malformations resulting from preconception paternal stressors, argue for the theoretical expansion of teratogenic perspectives into the male preconception period, and discuss some of the challenges in this newly emerging branch of toxicology. I argue that we must consider gametes the same as any other malleable precursor cell type and recognize that environmentally-induced epigenetic changes acquired during the formation of the sperm and oocyte hold equal teratogenic potential as exposures during early development. Here, I propose the term epiteratogen to reference agents acting outside of pregnancy that, through epigenetic mechanisms, induce congenital malformations. Understanding the interactions between the environment, the essential epigenetic processes intrinsic to spermatogenesis, and their cumulative influences on embryo patterning is essential to addressing a significant blind spot in the field of developmental toxicology.
直到最近，临床医生和研究人员才意识到父亲的暴露可能会影响儿童的发育结果。事实上，尽管越来越多的人认识到精子携带大量非基因组信息，而且父亲的压力源会影响下一代的健康，但毒理学家现在才开始探索父亲的暴露在发育异常和先天性畸形的发生率中的作用。在这篇评论中，我将简要总结一些描述由于受孕前父亲的压力源导致先天性畸形的研究，主张将致畸的观点从理论上扩展到男性受孕前阶段，并讨论毒理学这一新分支中存在的一些挑战。我认为，我们必须将配子视为与任何其他可塑前体细胞类型相同的物质，并认识到在精子和卵子形成过程中获得的环境诱导的表观遗传变化与早期发育过程中的暴露具有同等的致畸潜力。在这里，我提出了“epiteratogen”一词来指代在妊娠之外起作用的、通过表观遗传机制诱导先天性畸形的物质。了解环境、精子发生过程中内在的必需表观遗传过程之间的相互作用，以及它们对胚胎模式形成的累积影响，对于解决发育毒理学领域的一个重大盲点至关重要。
