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Updated: Apr 19, 2026
Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
Published on: June 17, 2015
Xenotransplantation models to study the effects of toxicants on human fetal tissues
Daniel J Spade1, Elizabeth V McDonnell, Nicholas E Heger
1Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island.
Abstract:
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.
Insights
Human fetal tissue xenotransplantation models offer new ways to study how environmental toxicants impact development and adult diseases. These models provide human-relevant data to assess risks from toxicant exposure during critical developmental periods.
Area of Science:
- Developmental toxicology
- Xenobiotic exposure
- Human fetal development
Background:
- Lifelong diseases can be influenced by fetal development factors.
- Fetal exposure to xenobiotics (foreign chemical substances) may impact adult disease development.
- Traditional animal models lack human-tissue relevance for toxicant mechanistic studies.
Purpose of the Study:
- To review the development of human fetal tissue xenotransplantation models.
- To explore their application in studying xenobiotic effects on tissue development.
- To understand implications for diseases like testicular dysgenesis, prostate disease, lung disease, and metabolic syndrome.
Main Methods:
- Development of human fetal tissue xenotransplantation models for key organs (testis, prostate, lung, liver, adipose).
- Utilizing these models to investigate mechanistic effects of toxicants on developing human tissues.
- Reviewing existing literature on xenotransplantation model development and application.
Main Results:
- Human fetal tissue xenotransplantation models provide human-relevant mechanistic data.
- These models allow assessment of toxicant effects on specific tissue development (e.g., testis, prostate, lung, liver, adipose).
- Data generated can inform understanding of disease origins, including testicular dysgenesis, prostate disease, lung disease, and metabolic syndrome.
Conclusions:
- Human fetal tissue xenotransplantation models are valuable tools for developmental toxicology.
- They offer a human-centric approach to complement existing research methods.
- Mechanistic data from these models aid in quantifying risks of toxicant exposures during human development.
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