Do environmental toxicants target signaling in spermatogonial stem cells?

Spermatogenesis;Spermatogonial Stem cells;mono-ethylhexyl-phthalate (MEHP);Nanoparticles;Toxicity;glial cell-line derived neutrotrophic factor (GDNF);Differentiation;Self-Renewal

Lucas, Benjamin

关键词: Spermatogenesis;    Spermatogonial Stem cells;    mono-ethylhexyl-phthalate (MEHP);    Nanoparticles;    Toxicity;    glial cell-line derived neutrotrophic factor (GDNF);    Differentiation;    Self-Renewal;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/42309/Benjamin_Lucas.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

male, and therefore to sustain spermatogenesis.There is a general lack of mechanistic insights on how particulate matter (or ultra fineparticles) alter male fertility. A few studies showed that ultra fine particles (UFP) and somenanoparticles (manufactured particles in the same range of size as UFPs) are able to crossbiological barriers such as the gut or the lung epithelium. After reaching the blood stream, theseparticles are distributed though the organism and eventually reach the testis and even cross theblood testis barrier. However, little is known about the possible targets. In the first part of thisdissertation, I demonstrated that silver nanoparticles (which are present in an increasing numberof commercial products), are toxic for spermatogonial stem cells by targeting glial cell-linederived neutrotrophic factor (GDNF) signaling leading to a decrease of proliferation.The decline of reproductive health has been clearly linked to a number of chemicals. Inparticular, plasticizers such as di-ethylhexyl-phthalate (DEHP) have been directly linked to adecrease of sperm count and other reproductive defects. There are a number of studiesshowing that DEHP and its metabolite mono-ethylhexyl-phthalate (MEHP) target somatic cells ofthe 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 effectsof DEHP or its metabolite MEHP on germ cells (spermatocyte), but none on spermatogonialstem cells (SSCs). I investigated whether MEHP could a have direct effect on spermatogonialstem cells, and found that MEHP was able to affect GDNF signaling pathway, leading to thedecrease of proliferation of these cells.Both types of toxicants were able to have a direct effect on the spermatogonial stemcells. In particular, exposure of SSCs to silver nanoparticles or MEHP lowered their ability toproliferate. This decreased SSC proliferation could lead to a reduction of spermatogenesis.