title: Xenotransplantation models to study the effects of toxicants on human fetal tissues.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Spade
authors.forename: Elizabeth V
authors.initials: EV
authors.lastname: McDonnell
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Heger
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Sanders
authors.forename: Camelia M
authors.initials: CM
authors.lastname: Saffarini
authors.forename: Philip A
authors.initials: PA
authors.lastname: Gruppuso
authors.forename: Monique E
authors.initials: ME
authors.lastname: De Paepe
authors.forename: Kim
authors.initials: K
authors.lastname: Boekelheide
mesh_terms: D000818:Animals; D047109:Fetal Development / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D023421:Models, Animal; D051381:Rats; D016378:Tissue Transplantation; D014183:Transplantation, Heterologous; D015262:Xenobiotics / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D015262:Xenobiotics
keywords: development; toxicity; xenobiotics; xenotransplants