Journal Article

Human Primordial Germ Cell Formation Is Diminished by Exposure to Environmental Toxicants Acting through the AHR Signaling Pathway

Kehkooi Kee, Martha Flores, Marcelle I. Cedars and Renee A. Reijo Pera

in Toxicological Sciences

Volume 117, issue 1, pages 218-224
Published in print September 2010 | ISSN: 1096-6080
Published online June 2010 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfq179

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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.

Keywords: human embryonic stem cells; germ cell differentiation; reproductive toxicology; polycyclic aromatic hydrocarbons; aromatic hydrocarbon receptor (AHR)

Journal Article.  3888 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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