Gonçalves Bianca M, Graceli Jones B, da Rocha Paula B, Tilli Helena P, Vieira Ester M, de Sibio Maria T, Peghinelli Vinícius V, Deprá Igor C, Mathias Lucas S, Olímpio Regiane M C, Belik Virgínia C, Nogueira Célia R
Department of Clinical Medicine, Medical School, São Paulo State University (UNESP), Botucatu, SP, Brazil.
Department of Morphology, Health Sciences Center, Federal University of Espirito Santo (UFES), Vitória, ES, Brazil.
Reprod Toxicol. 2022 Sep;112:7-13. doi: 10.1016/j.reprotox.2022.06.005. Epub 2022 Jun 14.
The placenta is a temporary organ that plays critical roles at the maternal-fetal interface. Normal development and function of the placenta is dependent on hormonal signaling pathways that make the placenta a target of endocrine disrupting chemical (EDC) action. Studies showing association between prenatal exposure, hormone disruption, and reproductive damage indicate that EDCs are developmentally toxic and can impact future generations. In this context, new placental models (trophoblast-derived cell lines, organotypic or 3D cell models, and physiologically based kinetic models) have been developed in order to create new approach methodology (NAM) to assess and even prevent such disastrous toxic harm in future generations. With the widespread discouragement of conducting animal studies, it has become irrefutable to develop in vitro models that can serve as a substitute for in vivo models. The goal of this review is to discuss the newest in vitro models to understand the maternal-fetal interface and predict placental development, physiology, and dysfunction generated by failures in molecular hormone control mechanisms, which, consequently, may change epigenetic programming to increase susceptibility to metabolic and other disorders in the offspring. We summarize the latest placental models for developmental toxicology studies, focusing mainly on three-dimensional (3D) culture models.
胎盘是一个临时器官，在母胎界面发挥着关键作用。胎盘的正常发育和功能依赖于激素信号通路，这使得胎盘成为内分泌干扰化学物质（EDC）作用的靶点。显示产前暴露、激素干扰和生殖损伤之间关联的研究表明，EDC具有发育毒性，会影响后代。在此背景下，已开发出新的胎盘模型（滋养层来源的细胞系、器官型或3D细胞模型以及基于生理学的动力学模型），以创建新的方法学（NAM）来评估甚至预防后代遭受此类灾难性的毒性伤害。随着广泛不鼓励进行动物研究，开发能够替代体内模型的体外模型已变得无可辩驳。本综述的目的是讨论最新的体外模型，以了解母胎界面并预测胎盘发育、生理学以及分子激素控制机制失败所产生的功能障碍，而这可能会改变表观遗传编程，增加后代对代谢和其他疾病的易感性。我们总结了用于发育毒理学研究的最新胎盘模型，主要侧重于三维（3D）培养模型。
