Impacts from Exposure to Common Chemical Pollutants on Neuroendocrine-Regulated Behavior and Related Gene Expression

EPA Grant Number: FP917143
Title: Impacts from Exposure to Common Chemical Pollutants on Neuroendocrine-Regulated Behavior and Related Gene Expression
Investigators: Miranda, Robert Alan
Institution: Northern Arizona University
EPA Project Officer: Michaud, Jayne
Project Period: August 30, 2010 through August 29, 2013
Project Amount: $111,000
RFA: STAR Graduate Fellowships (2010) RFA Text |  Recipients Lists
Research Category: Academic Fellowships , Fellowship - Pesticides and Toxic Substances


Sex steroids play a critical role in developmental and adult expression of behavior through actions on the brain that impact the arginine vasotocin (AVT)/vasopressin (AVP) systems. Although several studies have investigated how estrogenic endocrine disrupting compounds impact gonadal development, almost nothing is known about how exposure to environmental estrogens impacts the AVT/AVP signaling system. Using Xenopus tropicalis as a model species, the objectives of this project are 1) to determine whether adult exposure to a human exposure concentration of individual common endocrine disrupting compounds or a mix of these compounds impacts AVT-mediated vocal behavior and genes involved in estrogen and AVT signaling in the brain, and 2) to determine the impact of developmental exposure to endocrine disrupting compounds on AVT and neuro-estrogen signaling systems and on adult behavior.


Environmental pollutants can disrupt normal functioning of the endocrine system. These endocrine disruptors can impact an organism’s development, physiology, or behavior by mimicking or inhibiting natural hormone and chemical signaling. This project aims to understand how exposure to common environmental pollutants and the timing of exposure during an organism’s lifetime affects neuroendocrine regulated vertebrate social behavior and related gene expression using Xenopus tropicalis as a model.


This project will examine the impact of exposure to a single known contaminant or a complex mix of contaminants on AVT/AVP sensitive social behaviors. Working from behavior to gene expression, the exposure effects on AVT-signaling systems and on the estrogenic components that may be involved in regulating social behavior will be evaluated. Using male Western clawed frogs as an animal model, one study will examine the impact of adult exposure on AVT-regulated sexual behavior, including vocalizations, and brain expression of related genes. In another study, behavior and gene expression will be evaluated after males are exposed to contaminants during their development.

Expected Results:

Changes in vocal behavior and brain expression of related genes are expected after chemical exposure. Differential effects are also expected based on the time of exposure during the animal’s life. Results from this study may lead to a better understanding of 1) how estrogen regulates development of the AVT/AVP behavioral system, 2) the molecular mechanisms involved in how environmental estrogens can modulate behavior, 3) how the timing of exposure to these compounds during an animal’s life may be important in understanding their impacts, and 4) how mixes that are relevant to those found in human plasma impact behavior and neuroendocrine signaling processes.

Potential to Further Environmental/Human Health Protection:

By evaluating multiple neuroendocrine endpoints in the same individuals throughout their life history and linking these results to behavior, the outcome of this research may help to understand the impacts of exposure to different compounds found in the environment, as well as the importance of the timing of exposure to these compounds. Because the AVT/AVP signaling system is so tightly conserved across vertebrates, results from this study may be applicable to our understanding of the impacts of chemical exposure on wildlife species and on human health.

Supplemental Keywords:

endocrine disruptors, arginine vasotocin, arginine vasopressin, social behavior, vocalizations, Xenopus tropicalis, Western clawed frog,

Progress and Final Reports:

  • 2011
  • 2012
  • Final