Format

Send to

Choose Destination
Toxicol Sci. 2010 Sep;117(1):218-24. doi: 10.1093/toxsci/kfq179. Epub 2010 Jun 18.

Human primordial germ cell formation is diminished by exposure to environmental toxicants acting through the AHR signaling pathway.

Author information

1
Department of Obstetrics and Gynecology, Center for Human Embryonic Stem Cell Research and Education, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford University, Palo Alto, California, USA. kkee@mail.tsinghua.edu.cn

Abstract

Historically, effects of environmental toxicants on human development have been deduced via epidemiological studies because direct experimental analysis has not been possible. However, in recent years, the derivation of human pluripotent stem cells has provided a potential experimental system to directly probe human development. Here, we used human embryonic stem cells (hESCs) to study the effect of environmental toxicants on human germ cell development, with a focus on differentiation of the founding population of primordial germ cells (PGCs), which will go on to form the oocytes of the adult. We demonstrate that human PGC numbers are specifically reduced by exposure to polycyclic aromatic hydrocarbons (PAHs), a group of toxicants common in air pollutants released from gasoline combustion or tobacco smoke. Further, we demonstrate that the adverse effects of PAH exposure are mediated through the aromatic hydrocarbon receptor (AHR) and BAX pathway. This study demonstrates the utility of hESCs as a model system for direct examination of the molecular and genetic pathways of environmental toxicants on human germ cell development.

PMID:
20562217
PMCID:
PMC2923286
DOI:
10.1093/toxsci/kfq179
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center