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Effect of tobacco toxins on human germ cell development

Institution: University of California, San Francisco
Investigator(s): Kehkooi Kee, Ph.D.
Award Cycle: 2006 (Cycle 15) Grant #: 15FT-0178 Award: $33,290
Subject Area: General Biomedical Science
Award Type: Postdoctoral Fellowship Awards
Abstracts

Initial Award Abstract
Little is known about the effect of chemicals found in agents such as cigarette smoke on human germ cell (egg and sperm) development and the success of reproduction. A few studies have shown that cigarette smoking decreases the age at menopause in women. Yet, whether this is a direct or indirect effect on the germ cells themselves is not known. In this research plan, I will explore the use of human embryonic stem cells (hESCs) to study human germ cell development in the presence and absence of chemicals found in cigarette smoke. This system promises to provide an excellent opportunity to study environmental and genetic factors in human germ cell development, especially the early developmental stage from embryonic stem cells to primordial germ cells. In particular, over the last year, since I joined the Reijo Pera laboratory, I have been focused on the earliest events in germ cell development, whereas others have been focused on development of more mature oocytes. In particular, I have shown that germ cell development from human embryonic stem cells is responsive to growth factors that are known to be involved during normal fetal development in mice. My overall hypothesis that I wish to examine during my postdoctoral work is that human embryonic stem cells provide an excellent system to study the initial formation of germ cells and its susceptibility to genetic and environmental perturbation, including perturbation by toxins in smoke.

My specific aims are:

Aim 1: Enhance and characterize differentiation of hESCs to primordial germ cells in vitro.

Aim 2: Examine the effect of PAHs during in vitro differentiation of hESCs to primordial germ cells.

Aim 3: Silence AHR and BAX genes to probe the molecular pathway of PAHs effect on human germ cell development to primordial germ cells.

I expect that with the completion of my aims, I will have enhanced the use of hESC differentiation to primordial germ cells to study the effect of tobacco smoke in normal and mutant human embryonic stem cell lines. I also expect that other researchers will follow up on these results and increasingly turn to the human embryonic stem cell system to probe effects of environmental toxins including others in tobacco smoke.
Publications

Bone morphogenetic proteins induce grem cell differentiation from human embryonic stem cells
Periodical: Stem Cells Index Medicus:
Authors: Kehkooi, Kee ART
Yr: 2006 Vol: 15 Nbr: Abs: Pg: 831-7