Human primordial germ cell formation is diminished by exposure to environmental toxicants acting through the AHR signaling pathway.
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.
Kee
Kehkooi
K
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
Flores
Martha
M
Cedars
Marcelle I
MI
Reijo Pera
Renee A
RA
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002469:Cell Separation; D004785:Environmental Pollutants / Q000633:toxicity*; D005434:Flow Cytometry; D005854:Germ Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D051379:Mice; D011083:Polycyclic Compounds / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D004785:Environmental Pollutants; D011083:Polycyclic Compounds; D018336:Receptors, Aryl Hydrocarbon