Spade Daniel J, McDonnell Elizabeth V, Heger Nicholas E, Sanders Jennifer A, Saffarini Camelia M, Gruppuso Philip A, De Paepe Monique E, Boekelheide Kim
Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island.
Birth Defects Res B Dev Reprod Toxicol. 2014 Dec;101(6):410-22. doi: 10.1002/bdrb.21131. Epub 2014 Dec 4.
Many diseases that manifest throughout the lifetime are influenced by factors affecting fetal development. Fetal exposure to xenobiotics, in particular, may influence the development of adult diseases. Established animal models provide systems for characterizing both developmental biology and developmental toxicology. However, animal model systems do not allow researchers to assess the mechanistic effects of toxicants on developing human tissue. Human fetal tissue xenotransplantation models have recently been implemented to provide human-relevant mechanistic data on the many tissue-level functions that may be affected by fetal exposure to toxicants. This review describes the development of human fetal tissue xenotransplant models for testis, prostate, lung, liver, and adipose tissue, aimed at studying the effects of xenobiotics on tissue development, including implications for testicular dysgenesis, prostate disease, lung disease, and metabolic syndrome. The mechanistic data obtained from these models can complement data from epidemiology, traditional animal models, and in vitro studies to quantify the risks of toxicant exposures during human development.
许多在整个生命周期中表现出来的疾病都受到影响胎儿发育的因素的影响。特别是，胎儿接触外源性物质可能会影响成人疾病的发展。已建立的动物模型为表征发育生物学和发育毒理学提供了系统。然而，动物模型系统不允许研究人员评估毒物对发育中的人体组织的机制性影响。最近已实施人类胎儿组织异种移植模型，以提供与人类相关的机制数据，说明胎儿接触毒物可能影响的许多组织水平功能。本综述描述了用于睾丸、前列腺、肺、肝和脂肪组织的人类胎儿组织异种移植模型的发展，旨在研究外源性物质对组织发育的影响，包括对睾丸发育不全、前列腺疾病、肺部疾病和代谢综合征的影响。从这些模型中获得的机制数据可以补充来自流行病学、传统动物模型和体外研究的数据，以量化人类发育过程中接触毒物的风险。
