BeDa Consulting AB, Upplandsgatan 6, SE-111 23 Stockholm, Sweden.
Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Reprod Toxicol. 2023 Dec;122:108488. doi: 10.1016/j.reprotox.2023.108488. Epub 2023 Oct 16.
Teratogenicity and Reactive Oxygen Species after transient embryonic hypoxia: Experimental and clinical evidence with focus on drugs with human abortive potential. Reactive Oxygen Species (ROS) can be harmful to embryonic tissues. The adverse embryonic effects are dependent on the severity and duration of the hypoxic event and when during organongenesis hypoxia occurs. The vascular endothelium of recently formed arteries in the embryo is highly susceptible to ROS damage. Endothelial damage results in vascular disruption, hemorrhage and maldevelopment of organs, which normally should have been supplied by the artery. ROS can also induce irregular heart rhythm in the embryo resulting in alterations in blood flow and pressure from when the tubular heart starts beating. Such alterations in blood flow and pressure during cardiogenesis can result in a variety of cardiovascular defects, for example transpositions and ventricular septal defects. One aim of this article is to review and compare the pattern of malformations produced by transient embryonic hypoxia of various origins in animal studies with malformations associated with transient embryonic hypoxia in human pregnancy due to a failed abortion process. The results show that transient hypoxia and compounds with potential to cause failed abortion in humans, such as misoprostol and hormone pregnancy tests (HPTs) like Primodos, have been associated with a similar spectrum of teratogenicity. The spectrum includes limb reduction-, cardiovascular- and central nervous system defects. The hypoxia-ROS related teratogenicity of misoprostol and HPTs, is likely to be secondary to uterine contractions and compression of uterinoplacental/embryonic vessels during organogenesis.
实验和临床证据的重点是药物具有人类流产的潜力。活性氧(ROS)可能对胚胎组织有害。胚胎的不良影响取决于缺氧事件的严重程度和持续时间，以及缺氧发生的时间。胚胎中最近形成的动脉的血管内皮对 ROS 损伤非常敏感。内皮损伤导致血管破裂、出血和器官发育不良，而这些器官通常应该由动脉供应。ROS 还可以在胚胎中诱导不规则的心律，导致管状心脏开始跳动时血流和压力的改变。这种在心脏发生过程中血流和压力的改变可导致多种心血管缺陷，例如转位和室间隔缺损。本文的目的之一是回顾和比较各种来源的短暂胚胎缺氧在动物研究中产生的畸形模式，以及与人类妊娠中由于流产失败而导致的短暂胚胎缺氧相关的畸形。结果表明，短暂缺氧和具有人类流产潜力的化合物，如米索前列醇和激素妊娠试验(如 Primodos)，与类似的致畸谱有关。该谱包括肢体减少、心血管和中枢神经系统缺陷。米索前列醇和 HPTs 的缺氧-ROS 相关致畸性可能继发于子宫收缩和子宫胎盘/胚胎血管在器官发生期间的压迫。
