Rosenfeld Cheryl S
Biomedical Sciences, University of Missouri, Columbia, MO, United States.
MU Institute for Data Science and Informatics, University of Missouri, Columbia, MO, United States.
Front Cell Dev Biol. 2021 Sep 24;9:723656. doi: 10.3389/fcell.2021.723656. eCollection 2021.
The conceptus is most vulnerable to developmental perturbation during its early stages when the events that create functional organ systems are being launched. As the placenta is in direct contact with maternal tissues, it readily encounters any xenobiotics in her bloodstream. Besides serving as a conduit for solutes and waste, the placenta possesses a tightly regulated endocrine system that is, of itself, vulnerable to pharmaceutical agents, endocrine disrupting chemicals (EDCs), and other environmental toxicants. To determine whether extrinsic factors affect placental function, transcriptomics and other omics approaches have become more widely used. In casting a wide net with such approaches, they have provided mechanistic insights into placental physiological and pathological responses and how placental responses may impact the fetus, especially the developing brain through the placenta-brain axis. This review will discuss how such omics technologies have been utilized to understand effects of EDCs, including the widely prevalent plasticizers bisphenol A (BPA), bisphenol S (BPS), and phthalates, other environmental toxicants, pharmaceutical agents, maternal smoking, and air pollution on placental gene expression, DNA methylation, and metabolomic profiles. It is also increasingly becoming clear that miRNA (miR) are important epigenetic regulators of placental function. Thus, the evidence to date that xenobiotics affect placental miR expression patterns will also be explored. Such omics approaches with mouse and human placenta will assuredly provide key biomarkers that may be used as barometers of exposure and can be targeted by early mitigation approaches to prevent later diseases, in particular neurobehavioral disorders, originating due to placental dysfunction.
在胚胎发育早期，当构建功能器官系统的过程启动时，胚胎最容易受到发育干扰。由于胎盘与母体组织直接接触，它很容易接触到母体血液中的任何外源性物质。除了作为溶质和废物的传输通道外，胎盘还拥有一个严格调控的内分泌系统，其本身就容易受到药物、内分泌干扰化学物质（EDCs）和其他环境毒物的影响。为了确定外在因素是否会影响胎盘功能，转录组学和其他组学方法得到了更广泛的应用。通过这些方法广泛搜罗信息，它们为胎盘的生理和病理反应以及胎盘反应如何通过胎盘 - 脑轴影响胎儿，尤其是发育中的大脑，提供了机制性见解。本综述将讨论这些组学技术是如何被用于理解EDCs的影响，包括广泛存在的增塑剂双酚A（BPA）、双酚S（BPS）和邻苯二甲酸盐、其他环境毒物、药物、母亲吸烟和空气污染对胎盘基因表达、DNA甲基化和代谢组学图谱的影响。越来越明显的是，微小RNA（miR）是胎盘功能的重要表观遗传调节因子。因此，还将探讨迄今为止关于外源性物质影响胎盘miR表达模式的证据。利用小鼠和人类胎盘的这些组学方法肯定会提供关键的生物标志物，这些标志物可作为暴露的晴雨表，并可成为早期缓解措施的目标，以预防因胎盘功能障碍引发的后期疾病，特别是神经行为障碍。
