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The unique applicability of the human placenta to the Adverse Outcome Pathway (AOP) concept: the placenta provides fundamental insights into human organ functions at multiple levels of biological organization.
Reproductive Toxicology ( IF 3.3 ) Pub Date : 2020-08-05 , DOI: 10.1016/j.reprotox.2020.07.014
Claudia Gundacker 1 , Isabella Ellinger 2
Affiliation  

Despite the short lifespan of the human placenta, the proper formation and function of the organ is of crucial importance for fetal development. Placental dysfunction increases the risk of complications for mother and child during pregnancy and childbirth and beyond as it predisposes to fetal programming. The placenta is an upstream organ of the fetus. It performs the functions of fetal lungs, liver, intestines, kidneys and glands as long as these organs are not fully functional. Furthermore, it is the only human organ that is non-invasively available either after elective abortion or after birth. This is a crucial point given that the conceptual framework of Adverse Outcome Pathway (AOP) requires data on organ function. In vitro and ex vivo placental studies, combined with epidemiological and clinical data on pregnant women, newborns, and infants can uniquely cover all levels of information needed to develop new AOPs and complement existing AOPs related to reproductive toxicity and beyond. To stimulate further research in this area and to support researchers in future studies dealing with the development of AOPs related to the placenta, this review first gives a brief description of placental structure, placental development and relevant pregnancy diseases. The state of knowledge about the available placental models, their particularities and limitations are briefly discussed. Finally, the use of placental research for the development of AOPs is presented with an illustrative example.



中文翻译:

人类胎盘对不良结果通路 (AOP) 概念的独特适用性:胎盘在生物组织的多个层面提供了对人体器官功能的基本见解。

尽管人类胎盘的寿命很短,但器官的正常形成和功能对于胎儿发育至关重要。胎盘功能障碍增加了母亲和孩子在怀孕和分娩期间及以后发生并发症的风险,因为它容易导致胎儿发育。胎盘是胎儿的上游器官。只要这些器官功能不全,它就会发挥胎儿肺、肝、肠、肾和腺体的功能。此外,它是唯一在选择性流产后或出生后无创可用的人体器官。鉴于不良结果途径 (AOP) 的概念框架需要器官功能数据,这是一个关键点。体外离体胎盘研究,结合孕妇、新生儿和婴儿的流行病学和临床数据,可以独特地涵盖开发新 AOP 所需的所有信息水平,并补充与生殖毒性及其他相关的现有 AOP。为了激发该领域的进一步研究并支持研究人员在未来研究与胎盘相关的 AOPs 的发展,本综述首先简要描述了胎盘结构、胎盘发育和相关的妊娠疾病。简要讨论了有关可用胎盘模型的知识状况、它们的特殊性和局限性。最后,通过一个说明性示例介绍了胎盘研究在 AOP 开发中的应用。

更新日期:2020-08-09
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