Effects of Atrazine on Rhesus Monkey & Human Pluripotent Stem Cells and Differentiating Male Germ Cells in Vitro Open Access

Abstract

Each year, there are approximately five million people exposed to herbicide atrazine (ATZ) via contaminated drinking water. Unfortunately, current research mostly focused on high-dose and relatively short-term exposure of ATZ to examine acute effects on animals and cells. Therefore, these studies might not fully recapitulate the effects of chronic ATZ exposure on human health. Additionally, there was only a limited number of studies examining the impact of ATZ on early development and the association between individuals with pre-existing genetic conditions and their susceptibility to the environmental toxicants. We proposed to examine the developmental toxicity of ATZ by exposing rhesus monkey embryonic stem cells (rESCs) and human induced pluripotent stem cells (hiPSCs) with Huntington’s disease (HD) or without HD (wild-type; WT) to various ATZ concentrations (0.3 and/or 30 μΜ) and exposure times (15 and/or 30 days). In addition to assessing the impact of ATZ on cell properties including pluripotency, apoptosis, and cell cycle, rESCs were also differentiated into spermatogonial stem cells (rSSCs) to examine the effects of ATZ on male germ cell development in vitro. Our findings suggested that 30 μΜ ATZ impacted cell cycle progression of WT-hiPSCs evidenced by the downregulation of cell cycle promoter genes CCNB1 and CDK1, despite no significant impact on pluripotency or apoptosis in rESCs and hiPSCs. Additionally, we found dysregulation of apoptotic markers before and after differentiation under ATZ exposure with no major effect on spermatogenesis in vitro. Lastly, we noticed that WT-hiPSCs were susceptible to 30 days treatment of higher dose of ATZ (30 μΜ), whereas HD-hiPSCs with larger trinucleotide expansion were susceptible to lower dose of ATZ (0.3 μΜ) in 15 days. Our study shed new light on the importance of toxicant concentrations, exposure times, the effector cell types, and individuals who had pre-existing health conditions in response to environmental toxicants. We laid the groundwork of developing a stem cell model to investigate the impact of environmental toxicant exposure on human health for the future studies on ATZ.

Table of Contents

Abstract ..........................1

Background......................3

Objectives........................6

Research Questions...........8

Materials and Methods......9

Highlights.......................13

Results............................13

Discussion.......................19

Figures............................25

References.......................45

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience Health Sciences, Public Health Biology, Cell
Keyword	Huntington's disease Stem cells Herbicide Germ cells Atrazine
Committee Chair / Thesis Advisor	Chan, Anthony W.S., Emory University
Committee Members	Barr, Dana B., Emory University Shepherd, Iain T., Emory University

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