Environmental nitrite and endocrine disruption

North Carolina State University, Raleigh NC

Investigators

Abstract

Nitrate pollution due to human activities (such as extensive use of fertilizers) is a global concern in freshwater and marine environments. Some negative impacts of nitrate pollution are well known--for example, extensive algal blooms or formation of the oxygen-deprived "dead zones" in nutrient-polluted waters. However, some of the dangers posed by excess nitrates may be more subtle and occur at much lower nitrate concentrations. The present study will investigate such novel mechanism of the impacts of low-level nitrate pollution on freshwater ecosystems which may be caused by conversion of nitrate into a potent signaling molecule--nitric oxide--which affects key cellular and physiological functions in a variety of organisms including humans. The PI will use a common freshwater organism--a water flea--to determine how nitric oxide derived from the nitrate found in the environment affects development, growth and reproduction. This study will provide novel insights into the effects of nitrate pollution on freshwater ecosystems and can have implications for understanding of the effects of excessive use of fertilizers on the health of freshwater ecosystems and the organisms that depend on them (including humans). Human activities have significantly modified the Earth's nitrogen cycle. The amount of nitrogen that is biologically available in ecosystems has dramatically increased through commercial nitrogen fixation for the production of fertilizers. The benefits associated with increased food production resulting from the use of synthetic fertilizers have been tempered by nitrogen pollution resulting in regional loss of water quality and biodiversity. Recent studies have revealed that levels of nitrates in the environment, previously considered to be safe, can be converted to the potent signaling molecule, nitric oxide, which may interfere with processes such as development, growth, and reproduction. Using state-of-the-art technologies in molecular biology, the mechanism by which nitric oxide, derived from environmental nitrate, interferes with embryo development will be established. The study will be conducted using a model crustacean species, Daphnia pulex; however, the mechanistic information obtained will be useful for the assessment of hazards associated with low-level nitrate exposure on other species, including humans. The first aim of this research will be to determine the molecular mechanism by which environmentally derived nitric oxide interferes with hormone signaling pathways, and is specifically focused on the interactions of nitric oxide with two nuclear receptors. The second aim will be to extend the molecular studies to whole organism evaluations of the consequences of nitric oxide exposure on specific aspects of embryo development. The final aim will be to quantify the population-level consequences of environmentally derived nitric oxide as shown in the previous aims to interfere with specific aspects of embryo development. Results from this research will provide a mechanistic understanding of how environmentally relevant levels of nitrate could result in declines in some wildlife populations through the dysregulation of molecular signaling processes critical to population sustainability. This study also will support an ambitious research-based outreach activity aimed at identifying variables that impact nitrate levels in the natural environmental. This outreach effort will provide mentoring training to graduate students and hands-on field and laboratory research experience for undergraduate students.