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Title:Do environmental toxicants target signaling in spermatogonial stem cells?
Author(s):Lucas, Benjamin
Director of Research:Hofmann, Marie-Claude
Doctoral Committee Chair(s):Hofmann, Marie-Claude
Doctoral Committee Member(s):Flaws, Jodi A.; Nowak, Romana A.; Miller, David J.; Hess, Rex A.
Department / Program:Comparative Biosciences
Discipline:Veterinary Medical Sciences, Comparative Biosciences
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Spermatogenesis
Spermatogonial Stem cells
mono-ethylhexyl-phthalate (MEHP)
Nanoparticles
Toxicity
glial cell-line derived neutrotrophic factor (GDNF)
Differentiation
Self-Renewal
Abstract:male, and therefore to sustain spermatogenesis. There is a general lack of mechanistic insights on how particulate matter (or ultra fine particles) alter male fertility. A few studies showed that ultra fine particles (UFP) and some nanoparticles (manufactured particles in the same range of size as UFPs) are able to cross biological barriers such as the gut or the lung epithelium. After reaching the blood stream, these particles are distributed though the organism and eventually reach the testis and even cross the blood testis barrier. However, little is known about the possible targets. In the first part of this dissertation, I demonstrated that silver nanoparticles (which are present in an increasing number of commercial products), are toxic for spermatogonial stem cells by targeting glial cell-line derived neutrotrophic factor (GDNF) signaling leading to a decrease of proliferation. The decline of reproductive health has been clearly linked to a number of chemicals. In particular, plasticizers such as di-ethylhexyl-phthalate (DEHP) have been directly linked to a decrease of sperm count and other reproductive defects. There are a number of studies showing that DEHP and its metabolite mono-ethylhexyl-phthalate (MEHP) target somatic cells of the testis, leading to the decrease of reproductive fitness and reproductive tract defects. However, at the time this project was started, there was only one study looking at direct effects of DEHP or its metabolite MEHP on germ cells (spermatocyte), but none on spermatogonial stem cells (SSCs). I investigated whether MEHP could a have direct effect on spermatogonial stem cells, and found that MEHP was able to affect GDNF signaling pathway, leading to the decrease of proliferation of these cells. Both types of toxicants were able to have a direct effect on the spermatogonial stem cells. In particular, exposure of SSCs to silver nanoparticles or MEHP lowered their ability to proliferate. This decreased SSC proliferation could lead to a reduction of spermatogenesis.
Issue Date:2013-02-03
URI:http://hdl.handle.net/2142/42309
Rights Information:Copyright 2012 Benjamin Lucas
Date Available in IDEALS:2013-02-03
Date Deposited:2012-12


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