@article{corniuk_lynch_arendt_braun-mcneill_owens_valverde_kucklick_mcclellan-green_2023, title={Using Plasma Vitellogenin in Loggerhead Sea Turtles to Assess Reproductive Maturation and Estrogen-Like Contaminant Exposure}, ISSN={["1552-8618"]}, DOI={10.1002/etc.5612}, abstractNote={AbstractVitellogenin (VTG), an egg yolk precursor, is abnormally produced by male and juvenile oviparous species after exposure to estrogens. Plasma VTG in loggerhead sea turtles (Caretta caretta) helped us understand their reproductive maturation and investigate it as a biomarker of contaminant exposure. The presence of VTG was screened in plasma from 404 loggerheads from the northwestern Atlantic Ocean using a freshwater turtle antibody in western blots. The concentrations of VTG were semiquantified using band intensities calibrated to results from a loggerhead antibody enzyme‐linked immunoassay. The detection and concentrations of VTG were in (from highest to lowest): nesting females, in‐water adult females, subadult females, smaller females, unknown sex, and males. Loggerheads from this region begin vitellogenesis at ≅77 cm straight carapace length. We classified VTG expression as abnormal in nine male or juvenile turtles. Organochlorine contaminant (OC) concentrations were measured in blood and/or fat biopsies of some turtles. One abnormal VTG female had the second highest fat polychlorinated biphenyl (PCB) and 4,4′‐dichlorodiphenyldichloroethylene concentrations compared among 43 VTG‐negative juveniles. The nine VTG‐abnormal turtles had average blood PCB concentrations 8.5% higher, but not significantly different, than 46 VTG‐negative juveniles (p = 0.453). In turtles less than 77 cm, blood PCB concentrations were significantly, but weakly, correlated with semiquantified VTG concentrations (tau = 0.1, p = 0.004). Greater blood OC concentrations were found in adult females than in males, which motivated the creation of a conceptual model of OC, VTG, and hormone concentrations across a reproductive cycle. A decision tree is also provided incorporating VTG as a sexing tool. Abnormal VTG expression cannot conclusively be linked to endocrine disruption caused by these OC concentrations. Studies should further investigate causes of abnormal VTG expression in wild sea turtles. Environ Toxicol Chem 2023;42:1309–1325. © 2023 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.}, journal={ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY}, author={Corniuk, Raquel N. and Lynch, Jennifer M. and Arendt, Michael D. and Braun-McNeill, Joanne and Owens, David W. and Valverde, Roldan A. and Kucklick, John R. and McClellan-Green, Patricia D.}, year={2023}, month={May} }
 @article{harms_mcclellan-green_godfrey_christiansen_broadhurst_godard-codding_2019, title={Crude Oil and Dispersant Cause Acute Clinicopathological Abnormalities in Hatchling Loggerhead Sea Turtles (Caretta caretta)}, volume={6}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2019.00344}, abstractNote={Following the explosion of the Deepwater Horizon MC252 oil rig in 2010, 319 live sea turtles exposed to crude oil and oil-dispersant (Corexit) combinations were admitted to rehabilitation centers for decontamination and treatment. Treatment of oiled sea turtles was guided by expected physiological and pathological effects of crude oil exposure extrapolated from studies in other species and from a single loggerhead sea turtle (Caretta caretta) study. While invaluable starting points, inherent limitations to extrapolation, and small sample size of the experimental exposure study, reduce their utility for clinical guidance and for assessing oil spill impacts. Effects of dispersants were not included in the previous experimental exposure study, and cannot be effectively isolated in the analysis of field data from actual spills. A terminal study of pivotal temperature of sex determination using eggs salvaged from doomed loggerhead nests provided an opportunity for an ancillary exposure study to investigate the acute effects of crude oil, dispersant, and a crude oil/dispersant combination in sea turtle hatchlings. Eggs were incubated at 27.2–30.8°C, and hatchlings were randomly assigned to control, oil, dispersant, and combined oil/dispersant exposures for 1 or 4 days. Contaminant exposures were started after a 3 day post-hatching period simulating nest emergence. Turtles were placed in individual glass bowls containing aged seawater and exposed to oil (Gulf Coast—Mixed Crude Oil Sweet, CAS #8002-05-9, 0.833 mL/L) and/or dispersant (Corexit 9500A, 0.083 mL/L), replicating concentrations encountered during oil spills and subsequent response. Statistically significant differences between treatments and non-exposed controls were detected for PCV, AST, uric acid, glucose, calcium, phosphorus, total protein, albumin, globulin, potassium, and sodium. The principal dyscrasias reflected acute osmolar, electrolyte and hydration challenges that were more numerous and greater in combined oil/dispersant exposures at 4 days. Clinicopathological findings were supported by a failure to gain weight (associated with normal hatchling hydration in seawater) in dispersant and combination exposed hatchlings. These findings can help guide clinical response for sea turtles exposed to crude oil and crude oil/dispersant combinations, and indicate potential impacts on wildlife to consider when deploying dispersants in an oil spill response.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Harms, Craig A. and McClellan-Green, Patricia and Godfrey, Matthew H. and Christiansen, Emily F. and Broadhurst, Heather J. and Godard-Codding, Celine A. J.}, year={2019}, month={Oct} }
 @article{bembenek-bailey_niemuth_mcclellan-green_godfrey_harms_gracz_stoskopf_2019, title={NMR Metabolomic Analysis of Skeletal Muscle, Heart, and Liver of Hatchling Loggerhead Sea Turtles (Caretta caretta) Experimentally Exposed to Crude Oil and/or Corexit}, volume={9}, ISSN={2218-1989}, url={http://dx.doi.org/10.3390/metabo9020021}, DOI={10.3390/metabo9020021}, abstractNote={We used nuclear magnetic spectroscopy (NMR) to evaluate the metabolic impacts of crude oil, Corexit 5900A, a dispersant, and a crude oil Corexit 5900A mixture exposure on skeletal muscle, heart, and liver physiology of hatchling loggerhead sea turtles (Caretta caretta). Tissue samples were obtained from 22 seven-day-old hatchlings after a four day cutaneous exposure to environmentally relevant concentrations of crude oil, Corexit 5900A, a combination of crude oil and Corexit 9500A, or a seawater control. We identified 38 metabolites in the aqueous extracts of the liver, and 30 metabolites in both the skeletal and heart muscle aqueous extracts, including organic acids/osmolytes, energy compounds, amino acids, ketone bodies, nucleosides, and nucleotides. Skeletal muscle lactate, creatines, and taurine concentrations were significantly lower in hatchlings exposed to crude oil than in control hatchlings. Lactate, taurine, and cholines appeared to be the basis of some variation in hatchling heart samples, and liver inosine, uracil, and uridine appeared to be influenced by Corexit and crude oil exposure. Observed decreases in concentrations of lactate and creatines may reflect energy depletion in skeletal muscle of oil-exposed animals, while decreased taurine concentrations in these animals may reflect higher oxidative stress.}, number={2}, journal={Metabolites}, publisher={MDPI AG}, author={Bembenek-Bailey, Stasia and Niemuth, Jennifer and McClellan-Green, Patricia and Godfrey, Matthew and Harms, Craig and Gracz, Hanna and Stoskopf, Michael}, year={2019}, month={Jan}, pages={21} }
 @article{bjornsdottir-butler_green_bolton_mcclellan-green_2015, title={Control of Histamine-Producing Bacteria and Histamine Formation in Fish Muscle by Trisodium Phosphate}, volume={80}, ISSN={["1750-3841"]}, DOI={10.1111/1750-3841.12875}, abstractNote={AbstractScombrotoxin fish poisoning remains the primary cause of seafood poisoning outbreaks despite preventive guidelines. The purpose of this study was to investigate the use of pH for the control of growth and histamine formation by histamine‐producing bacteria in fish muscle. We examined pH effects on growth and histamine formation in tuna fish infusion broth and in inoculated tuna and mahi‐mahi fish muscle. Histamine production was significantly less for all bacterial strains at pH 8.5 compared to pH 5.5 in tuna fish infusion broth with no significant difference in growth. Elevated pH due to phosphate treatment of fish muscle tissues significantly reduced histamine formation with no effect on the growth of histamine‐producing bacteria. This study revealed that phosphate treatment of mahi‐mahi and tuna fish muscle resulted in significantly lower histamine production over 4 d of storage at 10 °C. Phosphate treatment of fish muscle may serve as a secondary barrier in addition to FDA recommended time and temperature controls for reducing public health concerns of scombrotoxin fish poisoning.}, number={6}, journal={JOURNAL OF FOOD SCIENCE}, author={Bjornsdottir-Butler, Kristin and Green, David P. and Bolton, Greg E. and McClellan-Green, Patricia D.}, year={2015}, month={Jun}, pages={M1253–M1258} }
 @article{blickley_matson_vreeland_rittschof_di giulio_mcclellan-green_2014, title={Dietary CdSe/ZnS quantum dot exposure in estuarine fish: Bioavailability, oxidative stress responses, reproduction, and maternal transfer}, volume={148}, journal={Aquatic Toxicology (Amsterdam, Netherlands)}, author={Blickley, T. M. and Matson, C. W. and Vreeland, W. N. and Rittschof, D. and Di Giulio, R. T. and McClellan-Green, P. D.}, year={2014}, pages={27–39} }
 @article{romano_rittschof_mcclellan-green_holm_2010, title={Variation in toxicity of copper pyrithione among populations and families of the barnacle, Balanus amphitrite}, volume={26}, number={3}, journal={Biofouling}, author={Romano, J. A. and Rittschof, D. and McClellan-Green, P. D. and Holm, E. R.}, year={2010}, pages={341–347} }
 @article{blickley_mcclellan-green_2008, title={Toxicity of aqueous fullerene in adult and larval Fundulus heteroclitus}, volume={27}, ISSN={["1552-8618"]}, DOI={10.1897/07-632.1}, abstractNote={AbstractAqueous suspensions of fullerene aggregates (aqua‐nC60) were used to investigate the movement of carbon‐based nanomaterials in a marine water column and to determine their effects on different life stages of a marine teleost. Fullerene aggregates formed precipitates as a result of mixing in natural seawater, and levels of aqua‐nC60 were significantly increased in bottom waters after 24 h. Exposure of Fundulus heteroclitus embryos, larvae, and adults to increasing concentrations of aqua‐nC60 resulted in very little mortality, and no median lethal concentrations could be calculated at ≤ 10 mg/L. Aggregates of aqua‐nC60 did adhere to the chorion but did not affect development of the embryos or their hatching success. Movements of aqua‐nC60 through the chorion and into the embryo tended to increase with higher exposure levels; however, the concentrations were extremely low and did not differ significantly. Larvae exposed to increasing concentrations of aqua‐nC60 exhibited a significant dose‐dependent increase in total glutathione (GSH). This was accompanied by a decreasing trend in lipid peroxidation (LPO), but LPO was not statistically different between treatments. Adult F. heteroclitus exposed to increasing concentrations of aqua‐nC60 exhibited an increase in total GSH in liver tissue but not in the gill. No significant effects on LPO were observed in either tissue. Thus, we conclude that aqua‐nC60 affects the oxidative stress response of F. heteroclitus and that increased antioxidant defenses provide some physiological tolerance for these materials. Environmental factors influencing uptake, metabolism, and physiological response following exposure, however, need further investigation.}, number={9}, journal={ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY}, author={Blickley, Twyla Michelle and McClellan-Green, Patricia}, year={2008}, month={Sep}, pages={1964–1971} }
 @article{oberdorster_zhu_blickley_mcclellan-green_haasch_2006, title={Ecotoxicology of carbon-based engineered nanoparticles: Effects of fullerene (C-60) on aquatic organisms}, volume={44}, ISSN={["1873-3891"]}, DOI={10.1016/j.carbon.2005.11.008}, abstractNote={To more fully assess the toxicity of water-soluble fullerene (nC60), acute toxicity assays were performed on several environmentally relevant species. Included were the freshwater crustaceans Daphnia magna and Hyalella azteca, and a marine harpacticoid copepod, and two fish species, fathead minnow Pimephales promelas and Japanese medaka Oryzias latipes. The latter two species were used to assess sublethal effects of fullerene exposure by also assessing mRNA and protein expression in liver. Because prior studies found that both sonication and using tetrahydrofuran to solubilize fullerene increased the toxicity of nC60, the nC60 used in this study was prepared by stirring. For the invertebrate studies, nC60 could not be prepared at high enough concentration levels to cause 50% mortality (LC50) at 48 or 96 h. The maximum concentrations tested were 35 ppm for freshwater and 22.5 ppm for full-strength (35 ppt) seawater, since at higher concentrations the nC60 precipitated out of solution. Daphnia 21-day exposures resulted in a significant delay in molting and significantly reduced offspring production at 2.5 and 5 ppm nC60, which could possibly produce impacts at the population-level. For the fish, we found that neither the mRNA nor protein-expression levels of cytochrome P450 isozymes CYP1A, CYP2K1 and CYP2M1 were changed. The peroxisomal lipid transport protein PMP70 was significantly reduced in fathead minnow, but not medaka, indicating potential changes in acyl-CoA pathways.}, number={6}, journal={CARBON}, author={Oberdorster, E and Zhu, SQ and Blickley, TM and McClellan-Green, P and Haasch, ML}, year={2006}, month={May}, pages={1112–1120} }
 @article{keller_mcclellan-green_kucklick_keil_peden-adams_2006, title={Effects of organochlorine contaminants on loggerhead sea turtle immunity: Comparison of a correlative field study and in vitro exposure experiments}, volume={114}, ISSN={["0091-6765"]}, DOI={10.1289/ehp.8143}, abstractNote={Several laboratory and field studies indicate that organochlorine contaminants (OCs), such as poly-chlorinated biphenyls (PCBs) and pesticides, modulate immune responses in rodents, wildlife, and humans. In the present study we examined the effects of OCs on immunity in free-ranging loggerhead sea turtles (Caretta caretta). Mitogen-induced lymphocyte proliferation responses, lysozyme activity, and OC concentrations were measured from blood samples. Mitogens chosen in the lymphocyte proliferation assay were phytohemagglutinin (PHA) and concanavalin A (ConA) for T-lymphocyte stimulation, and lipopolysaccharide (LPS) and phorbol 12,13-dibutyrate (PDB) for B-lymphocyte stimulation. Lysozyme activity was significantly and negatively correlated with whole-blood concentrations of 4,4′-dichlorodiphenyldichloroethylene (4,4′-DDE) and the sum of chlordanes. Lymphocyte proliferation responses stimulated by PHA, LPS, and PDB were significantly and positively correlated with concentrations of the sum of PCBs measured in whole blood. LPS- and PDB-induced proliferation were also significantly and positively correlated with 4,4′-DDE blood concentrations. These correlative observations in free-ranging turtles suggest that current, chronic exposure to OCs may suppress innate immunity and enhance certain lymphocyte functions of loggerhead sea turtles. To further test this hypothesis, lymphocyte proliferation was measured after in vitro exposure of peripheral blood leukocytes from 16 turtles to Aroclor 1254 (0–13.5 μg/mL) or 4,4′-DDE (0–13.4 μg/mL). Both contaminants increased PHA- and PDB-induced proliferation at concentrations below those that affected cell viability. Moreover, the concentrations that enhanced PDB-induced proliferation in vitro were similar to concentrations measured in turtles with the highest proliferative responses. The similarities between the in vitro experiments and the correlative field study suggest that OC exposure modulates immunity in loggerhead turtles.}, number={1}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Keller, JM and McClellan-Green, PD and Kucklick, JR and Keil, DE and Peden-Adams, MM}, year={2006}, month={Jan}, pages={70–76} }
 @article{rittschof_mcclellan-green_2005, title={Molluscs as multidisciplinary models in environment toxicology}, volume={50}, ISSN={["1879-3363"]}, DOI={10.1016/j.marpolbul.2005.02.008}, abstractNote={The primary goal of this paper is to stimulate discussion and promote the use of mollusc models and multidisciplinary research approaches in the field of environmental toxicology. Molluscs are effective models because they are ubiquitous, have highly conserved control and regulatory pathways that are often homologous to vertebrate systems, and are extremely sensitive to anthropogenic inputs. We have attempted to provide initial references as an avenue into the literature and as a means for researchers to expand their thoughts to regions outside of their own area of expertise. The authors are particularly interested in developing multidisciplinary international collaborative efforts.}, number={4}, journal={MARINE POLLUTION BULLETIN}, author={Rittschof, D and McClellan-Green, P}, year={2005}, month={Apr}, pages={369–373} }
 @article{oberdorster_romano_mcclellan-green_2005, title={The neuropeptide APGWamide as a penis morphogenic factor (PMF) in gastropod mollusks}, volume={45}, ISSN={["1557-7023"]}, DOI={10.1093/icb/45.1.28}, abstractNote={Abstract The goal of this study was to further investigate the role of endogenous APGWamide levels in imposex induction in snails. APGWamide is a common neurotransmittor/neuromodulator peptide found in many species of molluscs, and is often related to sex organ growth or reproductive behavior. Mud snails (Ilyanassa obsoleta) were collected from the Rachel Carson Estuarine Reserve near Beaufort, NC, and were dosed with the environmental contaminant tributyltin (TBT), testosterone (T), or solvent vehicle (EtOH/ saline) controls. Both TBT and T have been shown previously to induce female snails to grow penises (a condition termed imposex), and to increase male penis size. Male normalized penis length was correlated to endogenous APGWamide levels (as measured by Western blotting of whole animal homogenates, r2 = 0.475), and control males had significantly higher APGWamide levels than control females. All TBT-treated animals, (male, female, and imposex) had levels of APGWamide similar to control males and significantly higher than control females. In testosterone treated animals, APGWamide levels were the same as controls and it is likely that testosterone interferes with a downstream signaling event to induce imposex. In addition, immunohistochemistry for APGWamide expression in abdominal areas was done on female, male and imposex snails collected from the wild. The pattern of APGWamide in imposex snails was similar to male snails, showing large patches of immuno-reactive areas in the top portion of the visceral mass. In female snails, no areas of cross-reactivity were found.}, number={1}, journal={INTEGRATIVE AND COMPARATIVE BIOLOGY}, author={Oberdorster, E and Romano, J and McClellan-Green, P}, year={2005}, month={Feb}, pages={28–32} }
 @article{keller_kucklick_stamper_harms_mcclellan-green_2004, title={Associations between organochlorine contaminant concentrations and clinical health parameters in loggerhead sea turtles from North Carolina, USA}, volume={112}, ISSN={["1552-9924"]}, DOI={10.1289/ehp.6923}, abstractNote={Widespread and persistent organochlorine (OC) contaminants, such as polychlorinated biphenyls (PCBs) and pesticides, are known to have broad-ranging toxicities in wildlife. In this study we investigated, for the first time, their possible health effects on loggerhead sea turtles (Caretta caretta). Nonlethal fat biopsies and blood samples were collected from live turtles for OC contaminant analysis, and concentrations were compared with clinical health assessment data, including hematology, plasma chemistry, and body condition. Concentrations of total PCBs (Sigma PCBs), Sigma DDTs, Sigma chlordanes, dieldrin, and mirex were determined in 44 fat biopsies and 48 blood samples. Blood concentrations of Sigma chlordanes were negatively correlated with red blood cell counts, hemoglobin, and hematocrit, indicative of anemia. Positive correlations were observed between most classes of OC contaminants and white blood cell counts and between mirex and Sigma TCDD-like PCB concentrations and the heterophil:lymphocyte ratio, suggesting modulation of the immune system. All classes of OCs in the blood except dieldrin were correlated positively with aspartate aminotransferase (AST) activity, indicating possible hepatocellular damage. Mirex and Sigma TCDD-like PCB blood concentrations were negatively correlated with alkaline phosphatase (ALP) activity. Significant correlations to levels of certain OC contaminant classes also suggested possible alteration of protein (increasing blood urea nitrogen, decreasing albumin:globulin ratio), carbohydrate (decreasing glucose), and ion (increasing sodium, decreasing magnesium) regulation. These correlations suggest that OC contaminants may be affecting the health of loggerhead sea turtles even though sea turtles accumulate lower concentrations of OCs compared with other wildlife.}, number={10}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Keller, JM and Kucklick, JR and Stamper, MA and Harms, CA and McClellan-Green, PD}, year={2004}, month={Jul}, pages={1074–1079} }
 @article{keller_mcclellan-green_2004, title={Effects of organochlorine compounds on cytochrome P450 aromatase activity in an immortal sea turtle cell line}, volume={58}, ISSN={["1879-0291"]}, DOI={10.1016/j.marenvres.2004.03.080}, abstractNote={Many classes of environmental contaminants affect the reproductive function of animals through interactions with the endocrine system. The primary components affected by endocrine active compounds (EACs) are the steroid receptors and the enzymes responsible for steroidogenesis. This study sought to develop an in vitro model for assessing EAC effects in sea turtles by examining their ability to alter cytochrome P450 aromatase (CYP19) activity. Aromatase is the enzyme responsible for the conversion of testosterone to estradiol. This enzyme is critical in the sexual differentiation of reptiles which demonstrate temperature-dependent sex determination. An immortal testis cell line GST-TS from a green sea turtle was grown in culture at 30 °C in RPMI 1640 media. The cells were exposed to three known aromatase inducers; dexamethasone (Dex), 8Br-cyclic AMP, or human chronic gonadotropin (HCG) and one aromatase inhibitor 4-androstenol-dione (4-OHA). In addition, the GST-TS cells were exposed to 0.1–30 μM atrazine and 3–100 μM 4,4′-DDE. The inducing compounds that have been shown to increase aromatase activity in other systems failed to induce aromatase activity in the GST-TS cells, yet exposure to the inhibiting compound, 4-OHA, did result in a significant reduction. Atrazine (0.1, 1.0 and 10 μM) significantly induced aromatase activity following a 24 h exposure, and 4,4′-DDE inhibited the activity but only at cytotoxic concentrations (100 μM). Based on these results, this in vitro model can be useful in examining the endocrine effects of EACs in sea turtles.}, number={2-5}, journal={MARINE ENVIRONMENTAL RESEARCH}, author={Keller, JM and McClellan-Green, P}, year={2004}, pages={347–351} }
 @article{keller_kucklick_mcclellan-green_2004, title={Organochlorine contaminants in loggerhead sea turtle blood: Extraction techniques and distribution among plasma and red blood cells}, volume={46}, number={2}, journal={Archives of Environmental Contamination and Toxicology (Online)}, author={Keller, J. M. and Kucklick, J. R. and McClellan-Green, P. D.}, year={2004}, pages={254–264} }
 @article{keller_kucklick_harms_mcclellan-green_2004, title={Organochlorine contaminants in sea turtles: Correlations between whole blood and fat}, volume={23}, ISSN={["0730-7268"]}, DOI={10.1897/03-254}, abstractNote={AbstractMonitoring toxic organochlorine(OC)compounds is an important aspect in wildlife studies, especially in protected species such as sea turtles. The goal of this study was to determine whether blood OC concentrations can predict those in adipose tissue of sea turtles. Blood offers many benefits for monitoring OCs. It can be collected nondestructively from live turtles and can be sampled repeatedly for continuous monitoring. Organochlorine concentrations in blood may better represent the exposure levels of target tissues, but blood concentrations may fluctuate more than those in fatty tissues following recent dietary exposure or lipid mobilization. Paired fat and blood samples were collected from 44 live, juvenile loggerhead sea turtles and 10 juvenile Kemp's ridley sea turtle carcasses. Organochlorines were analyzed using gas chromatography with electron capture detection and mass spectrometry. Lipid‐normalized OC concentrations measured in the blood significantly correlated to levels found in the fat samples of both species. This result suggests that sea turtle blood is a suitable alternative to fatty tissues for measuring OCs because blood concentrations reasonably represent those observed in the paired fat samples. However, blood OC concentrations calculated on a wet‐mass basis were significantly and inversely correlated to lipid content in the fat samples. Therefore, caution should be used when monitoring spatial or temporal trends, as OC levels may increase in the blood following mobilization of fat stores, such as during long migrations, breeding, or disease events.}, number={3}, journal={ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY}, author={Keller, JM and Kucklick, JR and Harms, CA and McClellan-Green, PD}, year={2004}, month={Mar}, pages={726–738} }
 @article{oberdorster_mcclellan-green_2002, title={Mechanisms of imposex induction in the mud snail, Ilyanassa obsoleta: TBT as a neurotoxin and aromatase inhibitor}, volume={54}, DOI={10.1016/S0141-1136(02)00118-6}, abstractNote={The occurrence of imposex, imposition of male sex characteristics on female snails, has been extensively documented throughout the world. Tributyltin (TBT) and other organotins have been causally linked to imposex induction at levels as low as 2 ng/l. There are several proposed mechanisms of action. First, TBT has been shown to be neurotoxic and to accumulate in snail ganglia. Peptide hormones control sexual differentiation in gastropods, and one hypothesis is that TBT acts as a neurotoxin to abnormally release the peptide hormone Penis Morphogenic Factor (PMF). However, PMF has not been characterized to date. The neuropeptide APGWamide significantly induces imposex in the mud snail, Ilyanassa obsoleta, at 10(-16) moles sub-cutaneous (SQ) injection over 2 weeks, and could be the PMF in this species. A second hypothesis is that TBT inhibits aromatase activity leading to increased testosterone levels and decreased estradiol. In vitro studies with snail digestive gland microsomes showed that TBT-dosed snails not exhibiting imposex had a 52% reduction in aromatase activity. Although the role of vertebrate sex steroids is not known in gastropods, it is possible that the combination of changes in peptide and steroid hormones may lead to imposex induction at extremely low doses of TBT.}, number={3-5}, journal={Marine Environmental Research}, author={Oberdorster, E. and McClellan-Green, P.}, year={2002}, pages={715–718} }