Research Statement
Krista A. McCoy
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Endocrine disrupting chemicals (EDCs) are ubiquitous environmental pollutants that negatively affect a variety of physiological, behavioral and developmental processes that are regulated by the endocrine system. For example, endocrine signaling regulates reproductive system development and plays an important role in organizing embryonic tissues so that they can respond to hormonal signals later in life, driving the establishment of sexual dimorphisms in gonads, brains, skin and other tissues. Exposure to EDCs that alter normal hormonal signaling during embryonic development can therefore permanently alter reproductive system morphology and function as well as reproductive behavior of adults. Importantly, many components of the endocrine system are highly conserved across taxa and so EDCs potentially have generalized and similar effects across vertebrates (including humans). Indeed, many studies have shown EDC consistent effects on the anatomy, behavior and reproductive system function of a wide array of vertebrate taxa. My research primarily focuses on amphibians because the entire class Amphibia is believed to be declining. In fact, one third of amphibian species are listed in the IUCN Red List categories of vulnerable, critically threatened, or endangered. Several strong lines of evidence demonstrate that pesticides are an important factor driving amphibian population declines and extinctions. The mechanisms, through which these declines are occurring and the role pesticides play in driving amphibian population declines more generally remain unknown. We do know, however, that wild amphibians, including those in pristine montane habitats where mass extinctions have been documented, are exposed to endocrine disrupting pesticides and that such chemicals affect the reproductive system of vertebrates, including amphibians. My dissertation research was the first study to conclusively demonstrate that gonadal abnormalities in amphibians increase with increasing agriculture, in a dose-dependent manner. This finding has influenced the direction of an important debate in the literature from determining whether amphibians have more gonadal abnormalities in agricultural areas to quantifying the implications of those abnormalities. Specifically, I showed that the proportion of intersexes (normally gonochoristic individuals having testes and ovaries), the severity of the intersexed condition, and the maximum number of gonadal abnormalities all increase significantly with increasing agriculture. In fact, 40% of toads with testes from highly agricultural sites also had ovaries (were intersexes), and 90% had at least one gonadal abnormality. I also showed that these gondal abnormalities were associated with altered gonadal function including altered gene expression profiles (DNA array and QPCR), reductions in circulating testosterone concentrations (Radioimmunoassay), sperm production (Histology), and reduced sexual dimorphism (Gross morphology--males looked like females at the agricultural sites) (McCoy et al 2008-http://www.ehponline.org/members/2008/11536/11536.pdf). Currently, I am integrating field and laboratory studies to investigate the ways in which environmentally relevant concentrations of pesticides influence reproductive physiology (e.g. sex hormone concentrations, gamete production), behavior (e.g. male signaling behavior and female preference) and success (e.g. fertilization success and larval performance) of túngara frogs. The túngara frog (Physalaemus pustulosus) is an excellent model organism for investigating how EDCs influence reproductive biology. Successful reproduction for males requires that they attract a receptive female by displaying. In frogs and toads this is achieved acoustically through calling. The females are attracted to calls of a particular quality and choose to mate with males after evaluating his calls. Call characteristics are in part modulated by sexually dimorphic laryngeal morphology, which is androgen (e.g., testosterone) dependent, and thus can be disrupted by pesticides that disrupt the endocrine system. The call of the túngara frog is characterized by a complex whine chuck and it is well established that females prefer males that whine and chuck over those that simply whine. The specific structure within the larynx that modulates this chuck (laryngeal fibrous mass) has recently been characterized, and might also be susceptible to hormone modulation. After attracting a mate, males must successfully fertilize the oocytes, via external fertilization, so paternity can be confidently established and fertilization success can be quantified in this system. Each step in the path to successful reproduction has been extensively studied in túngara frogs. In addition, túngara frogs are easily observable in the wild, can be easily maintained in captivity, and are amenable to experiments. For example, my collaborator Dr. Michael Ryan (University of Texas at Austin) has a well-established protocol for analyzing call characteristics in túngara frogs that has been used for many years to investigate various aspects of anuran communication. In fact, túngara frogs are one of the best-studied models of animal communication and reproductive behavior in the world (with ~ 200 papers written on túngara frog reproductive behavior, communication, and auditory system). This accumulated knowledge on túngara frog reproductive biology, including reproductive behavior and success, is an important baseline to establish “normal” variation in reproductive traits, something that is often lacking in toxicological studies. In addition, the túngara frog is ideal model for studying population level effects of EDCs because they go through their life cycle in one year thus all stages can be studied in a relatively short period of time. In fact, I am also collaborating with Dr. James Vonesh and Dr. Michael McCoy to develop broadly applicable population models parameterized with experimental data that will allow us to investigate which life history stages (tadpole or adult) and reproductive traits (e.g. reduced sperm counts or altered reproductive behavior) are most affected by EDC exposure. Over the next five years I will continue, exploring these questions by maintaining a strong quantitatively rigorous empirical approach, integrating field surveys, experiments and laboratory technologies. I will continue collaborating with scientists with complementary expertise to develop novel insights into the mechanisms and consequences of EDC exposure on reproductive biology and population persistence. Summary
of Current Projects
Field Surveys for Environmental Contamination, Panama: In collaboration with Dr. Roberto Ibanez (Smithsonian Tropical Research Institute and Universidad de Panamá), environmental chemist Dr. Frank Wania (University of Toronto), and Dr. Karen Warkentin (Boston University) I am beginning a study to determine the identities and concentrations of pesticides in forested areas of Panama where catastrophic amphibian declines have occurred and where declines are not known to have occurred, to assess whether amphibian population declines and extinctions in tropical montane regions are correlated with increased pesticide exposure, as they are in the United States. Effects of EDCs on reproductive physiology and behavior of túngara frogs: In collaboration with Dr. Michael Ryan (University of Texas) in the next rainy season (May 2009) I will experimentally contrast the reproductive effects (behavior, physiology, and reproductive success) of early (tadpole stage), late (after metamorphosis), and long term exposures (early+late) to ecologically relevant pesticides in an amphibian model system (Túngara frog). I will assess endpoints at multiple levels of organization (cellular, tissue, organ, individual, and population) to determine the contribution of different traits to decreased reproductive success. For example, pesticide exposure could reduce reproductive success because males can’t attract female mates (altered sexual selection) or because they have reduced sperm production (or both). The innovative approach that I have designed will allow us to reveal the specific life history stages and reproductive traits that are most sensitive to pesticide exposure and will identify the sub lethal mechanisms through which pesticides could be driving amphibian population declines. This will be one of the first and most detailed studies investigating the influence of endocrine disrupting pesticides on mate attraction, female choice, and sexual selection, and by highlighting a newly appreciated mechanism through which pesticides can modulate evolution and population ecology this project will change the paradigm of ecotoxicological studies on wildlife. Population Modeling: In collaboration with Dr. James Vonesh (Virginia Commonwealth University) and Dr. Michael McCoy (Boston University) I will use broadly applicable modeling, parameterized with experimental data, to explore how pesticide exposure on different amphibian life history stages affects specific reproductive traits (e.g. attracting a mate vs. fertilization success) and scales up to influence population health. This work will help identify which traits are most likely leading to population declines and will help conservation practitioners predict how seasonal changes in contaminant usage (e.g., decreased usage during the breeding season) might influence amphibian populations. Indeed, this work will also identify life history stages for focused conservation efforts and will help determine the most efficient ways that amphibian populations across the globe, including those suffering extinctions in the U.S. can be protected from EDC exposure. Gonadal abnormalities in Nile Perch (Lates niloticus) of Lake Victoria, Africa: In collaboration with Dr. Colette St Mary (University of Florida), Dr. Lauren Chapman (McGill University), and Winnie Nkalubo (Makerere University of Uganda and National Fisheries Resources Research Institute of Uganda) I am evaluating the gonadal morphology of Nile Perch, an extremely important African fishery, from Lake Victoria. Preliminary results suggest that Nile perch are suffering gonadal abnormalities that are consistent with endocrine disruption. Although a closely related taxa changes sex naturally our specimens do not exhibit morphology that resembles natural sex change and the size distribution of the intersex animals also does not support the hypothesis that the gonadal morphology we find is normal. Given the potential impact of this finding for the health of the fishery and the importance of the fishery for the local people we are expanding this study to include additional lakes (Lakes Nabugabo and potentially Albert) and are planning to write a proposal for funding to investigate this phenomenon in more detail. Effects of multiple pesticides on gonadal development of frogs: Dr. Jason Rohr (University of South Florida) recently conducted a large experiment where he exposed aquatic communities including several frog species to several different classes of pesticides (e.g. several herbicides and several insecticides). I am conducting gonadal histology on frogs which was not examined as part of the original study. This work is important because there is often low mortality after exposure to pesticides (at ecologically relevant concentrations), but might be high incidences of gonadal abnormalities. This experimental design allows us to contrast different types of pesticides and will help identify chemicals that induce fewer abnormalities. It is our hope and belief that provided with the proper information farmers will choose to use pesticides that cause fewer negative effects. Effects of early exposure to atrazine on gonadal form and function in streamside salamander (Ambystoma barbouri) juveniles: Dr. Brent Palmer (University of Kentucky), Dr. Jason Rohr and colleagues ran an experiment to determine if exposure to the herbicide atrazine, during the larval period of the streamside salamander induced carry over effects leading to reduced survival in older juveniles (Rohr et al, 2006). They found that there were significant carry over effects especially at lower concentrations. I will analyze gonadal morphology and spermatogenesis of these specimens to determine if atrazine also induced gonadal abnormalities. This work is important because there has been much debate in the literature about the effects of atrazine on amphibian gonadal morphology. |
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