{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T04:41:04Z","timestamp":1777524064219,"version":"3.51.4"},"reference-count":108,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T00:00:00Z","timestamp":1675641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The University of Southampton Faculty of Engineering and the Environment Graduate School"},{"DOI":"10.13039\/100007637","name":"Departamento Administrativo de Ciencia, Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["Call 646 (2014)"],"award-info":[{"award-number":["Call 646 (2014)"]}],"id":[{"id":"10.13039\/100007637","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Tri-Butyl Tin (TBT) remains as a legacy pollutant in the benthic environments. Although the toxic impacts and endocrine disruption caused by TBT to gastropod molluscs have been established, the changes in energy reserves allocated to maintenance, growth, reproduction and survival of European oysters\n                    <jats:italic>Ostrea edulis<\/jats:italic>\n                    , a target species of concerted benthic habitat restoration projects, have not been explored. This study was designed to evaluate the effect of TBT chloride (TBTCl) on potential ions and relevant metabolomic pathways and its association with changes in physiological, biochemical and reproductive parameters in\n                    <jats:italic>O<\/jats:italic>\n                    .\n                    <jats:italic>edulis<\/jats:italic>\n                    exposed to environmental relevant concentrations of TBTCl. Oysters were exposed to TBTCl 20 ng\/L (n = 30), 200 ng\/L (n = 30) and 2000 ng\/L (n = 30) for nine weeks. At the end of the exposure, gametogenic stage, sex, energy reserve content and metabolomic profiling analysis were conducted to elucidate the metabolic alterations that occur in individuals exposed to those compounds. Metabolite analysis showed significant changes in the digestive gland biochemistry in oysters exposed to TBTCl, decreasing tissue ATP concentrations through a combination of the disruption of the TCA cycle and other important molecular pathways involved in homeostasis, mitochondrial metabolism and antioxidant response. TBTCl exposure increased mortality and caused changes in the gametogenesis with cycle arrest in stages G0 and G1. Sex determination was affected by TBTCl exposure, increasing the proportion of oysters identified as males in\n                    <jats:italic>O<\/jats:italic>\n                    .\n                    <jats:italic>edulis<\/jats:italic>\n                    treated at 20ng\/l TBTCl, and with an increased proportion of inactive stages in oysters treated with 2000 ng\/l TBTCl. The presence and persistence of environmental pollutants, such as TBT, could represent an additional threat to the declining\n                    <jats:italic>O<\/jats:italic>\n                    .\n                    <jats:italic>edulis<\/jats:italic>\n                    populations and related taxa around the world, by increasing mortality, changing reproductive maturation, and disrupting metabolism. Our findings identify the need to consider additional factors (e.g. legacy pollution) when identifying coastal locations for shellfish restoration.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0280777","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T13:24:37Z","timestamp":1675689877000},"page":"e0280777","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Toxicity of tributyltin to the European flat oyster Ostrea edulis: Metabolomic responses indicate impacts to energy metabolism, biochemical composition and reproductive maturation"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2549-6711","authenticated-orcid":true,"given":"Lina M.","family":"Zapata-Restrepo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Hauton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm D.","family":"Hudson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian D.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Hauton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,2,6]]},"reference":[{"key":"pone.0280777.ref001","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0048-9697(00)00512-X","article-title":"Microbial interactions with tributyltin compounds: detoxification, accumulation, and environmental fate","volume":"258","author":"GM Gadd","year":"2000","journal-title":"Sci Total Environ"},{"key":"pone.0280777.ref002","volume-title":"Development of an integrated approach for the removal of tributyltin (TBT) from waterways and harbors: Prevention, treatment and reuse of TBT contaminated sediments","author":"K Pynaert","year":"2000"},{"issue":"3","key":"pone.0280777.ref003","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/etc.2108","article-title":"Detection, monitoring, and control of tributyltin-an almost complete success story","volume":"32","author":"P Matthiessen","year":"2013","journal-title":"Environ Toxicol Chem"},{"issue":"6","key":"pone.0280777.ref004","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1021\/es00171a001","article-title":"The fate of tributyltin in the aquatic environment","volume":"22","author":"EA Clark","year":"1988","journal-title":"Environ Sci Technol"},{"issue":"5","key":"pone.0280777.ref005","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1006\/ecss.1996.0036","article-title":"Persistence and Degradation Pathways of Tributyltin in Freshwater and Estuarine Sediments","volume":"42","author":"PH Dowson","year":"1996","journal-title":"Estuar Coast Shelf Sci"},{"issue":"3","key":"pone.0280777.ref006","doi-asserted-by":"crossref","first-page":"470","DOI":"10.7598\/cst2012.177","article-title":"Fate and Remediation of Organotin Compounds in Seawaters and Soils","volume":"1","author":"OS Ayanda","year":"2012","journal-title":"Chem Sci Trans"},{"issue":"12","key":"pone.0280777.ref007","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1021\/es00154a006","article-title":"Degradation of tributyltin in San Diego Bay, California, waters","volume":"20","author":"PF Seligman","year":"1986","journal-title":"Environ Sci Technol"},{"key":"pone.0280777.ref008","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0048-9697(00)00510-6","article-title":"Environmental impact of TBT: The French experience","volume":"258","author":"C. Alzieu","year":"2000","journal-title":"Sci Total Environ"},{"key":"pone.0280777.ref009","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/0141-1136(91)90043-8","article-title":"Organotin in the marine surface microlayer and subsurface waters of south-west England: Relation to toxicity thresholds and the UK environmental quality standard","volume":"32","author":"JJ Cleary","year":"1991","journal-title":"Mar Environ Res"},{"key":"pone.0280777.ref010","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0141-1136(91)90036-8","article-title":"Reductions in TBT concentrations in UK estuaries following legislation in 1986 and 1987","volume":"32","author":"ME Waite","year":"1991","journal-title":"Mar Environ Res"},{"issue":"2","key":"pone.0280777.ref011","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.marpolbul.2014.12.011","article-title":"Recovery from TBT pollution in English Channel environments: A problem solved?","volume":"95","author":"WJ Langston","year":"2015","journal-title":"Mar Pollut Bull"},{"key":"pone.0280777.ref012","doi-asserted-by":"crossref","first-page":"105303","DOI":"10.1016\/j.ocecoaman.2020.105303","article-title":"Should TBT continue to be considered an issue in dredging port areas? A brief review of the global evidence","volume":"197","author":"DD de Oliveira","year":"2020","journal-title":"Ocean Coast Manag"},{"issue":"11","key":"pone.0280777.ref013","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1016\/j.marpolbul.2008.07.011","article-title":"A survey of antifoulants in sediments from Ports and Marinas along the French Mediterranean coast","volume":"56","author":"R Cassi","year":"2008","journal-title":"Mar Pollut Bull"},{"issue":"2016","key":"pone.0280777.ref014","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.jclepro.2014.08.072","article-title":"Ecotoxicological risk assessment of antifouling emissions in a cruise ship port","volume":"121","author":"H Cari\u0107","year":"2016","journal-title":"J Clean Prod"},{"key":"pone.0280777.ref015","unstructured":"Solent European Marine Sites (SEMS). Annual Management Report. 2019. Available at: http:\/\/www.solentems.org.uk\/sems\/AMR\/SEMS_2019%20SSG_Comments.pdf (Last accessed 30 June 2022)."},{"key":"pone.0280777.ref016","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0048-9697(03)00329-2","article-title":"Accumulation of organotin compounds in Pacific oysters, Crassostrea gigas, collected from aquaculture sites in Taiwan","volume":"313","author":"MP Hsia","year":"2003","journal-title":"Sci Total Environ"},{"key":"pone.0280777.ref017","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.scitotenv.2005.01.016","article-title":"Toxicity and bioaccumulation of tributyltin and triphenyltin on oysters and rock shells collected from Taiwan maricuture area","volume":"349","author":"PJ Meng","year":"2005","journal-title":"Sci Total Environ"},{"issue":"1","key":"pone.0280777.ref018","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.chemosphere.2005.07.074","article-title":"Butyltin accumulation in the marine clam Mya arenaria: An evaluation of its suitability for monitoring butyltin pollution","volume":"63","author":"R Yang","year":"2006","journal-title":"Chemosphere"},{"key":"pone.0280777.ref019","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1016\/j.scitotenv.2018.09.310","article-title":"Organotin contamination in commercial and wild oysters from China: Increasing occurrence of triphenyltin","volume":"650","author":"C Chen","year":"2019","journal-title":"Sci Total Environ"},{"issue":"6","key":"pone.0280777.ref020","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1080\/09593330.2010.506201","article-title":"Shell thickening and chambering in the oyster Crassostrea gigas: Natural and anthropogenic influence of tributyltin contamination","volume":"32","author":"R Higuera-Ruiz","year":"2011","journal-title":"Environ Technol"},{"key":"pone.0280777.ref021","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3354\/meps113105","article-title":"Chronic toxicity of water tributyltin (TBT) and copper to spat of the bivalve Scrobicularia plana: Ecological implications","volume":"113","author":"JM Ruiz","year":"1994","journal-title":"Mar Ecol Prog Ser"},{"key":"pone.0280777.ref022","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/0048-9697(95)04670-5","article-title":"Laboratory and field investigations on the effects of organotin (tributyltin) on the oyster, Ostrea edulis","volume":"171","author":"V Axiak","year":"1995","journal-title":"Sci Total Environ"},{"key":"pone.0280777.ref023","first-page":"1081","article-title":"Effect of organotin compounds (TBT) used in antifouling paints on cultured marine molluscs\u2014a literature study","author":"M H\u00e9ral","year":"1989","journal-title":"Aquac Biotechnol Prog"},{"key":"pone.0280777.ref024","first-page":"1306","article-title":"Toxicity of TBT To Bivalves: Effects on Reproduction, Growth and Survival","author":"JE Thain","year":"1986","journal-title":"Ocean Conf Rec"},{"issue":"1","key":"pone.0280777.ref025","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.biochi.2013.10.002","article-title":"The mitochondrial F1FO-ATPase desensitization to oligomycin by tributyltin is due to thiol oxidation","volume":"97","author":"S Nesci","year":"2014","journal-title":"Biochimie"},{"key":"pone.0280777.ref026","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.envpol.2016.08.011","article-title":"Histopathological effect and stress response of mantle proteome following TBT exposure in the Hooded oyster Saccostrea cucullata","volume":"218","author":"P Khondee","year":"2016","journal-title":"Environ Pollut"},{"key":"pone.0280777.ref027","unstructured":"Perry F, Jackson A. Native oyster (Ostrea edulis). In Tyler-Walters H. and Hiscock K. (eds). MarLIN\u2014Mar Life Inf Netw Biol Sensit Key Inf Rev [on-line]. 2017."},{"key":"pone.0280777.ref028","unstructured":"Laing I, Walker P, Areal F. A Feasibility Study of Native Oyster (Ostrea Edulis) Stock Regeneration in the United Kingdom. CARD Project FC1016 Oyster Stock Regeneration -A Review of Biological, Technical and Economic Feasibility. 2005. Available at: https:\/\/www.seafish.org\/document\/?id=2976D1CB-0216-444E-A719-3F7EF69F51FB (Last accessed 30 June 2022)."},{"key":"pone.0280777.ref029","unstructured":"Harding S, Nelson L, Glover T. Solent Oyster Restoration Project. 2016. Available at: https:\/\/www.bluemarinefoundation.com\/wp-content\/uploads\/2015\/11\/20160525_Solent-Oyster-Restoration-Project_Management-Plan_Final-version.pdf (Last accessed 30 June 2022)."},{"issue":"5","key":"pone.0280777.ref030","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.marpolbul.2006.03.005","article-title":"Legal aspects of conserving native oysters in Scotland","volume":"52","author":"IP Smith","year":"2006","journal-title":"Mar Pollut Bull"},{"key":"pone.0280777.ref031","unstructured":"FAO. Global aquaculture production: Fisheries and Aquaculture Departament. 2019. Available at: http:\/\/www.fao.org\/fishery\/statistics\/global-aquaculture-production\/query\/es (Last accessed 30 June 2022)."},{"key":"pone.0280777.ref032","first-page":"184","article-title":"The ecology, conservation and history of the Solent","author":"CR Tubbs","year":"1999","journal-title":"Packard"},{"key":"pone.0280777.ref033","unstructured":"Key D, Davidson PE. A review of the development of the Solent oyster fishery 1972\u201380. Technical report. 1981. Available at: https:\/\/www.cefas.co.uk\/publications\/lableaflets\/lableaflet52.pdf (Last accessed 30 June 2022)."},{"key":"pone.0280777.ref034","unstructured":"Gravestock V, James F, Goulden M. Solent Native Oyster (Ostrea edulis) Restoration: Literature Review & Feasibility Study. 2014."},{"key":"pone.0280777.ref035","unstructured":"Southern Inshore Fisheries and Conservation Authority (IFCA). Solent Oyster Fishery 2018 Stock Survey Report. 2018. Available at: https:\/\/www.southern-ifca.gov.uk\/solent-dredge-permit (Last accessed 30 June 2022)."},{"key":"pone.0280777.ref036","unstructured":"Eagling LE. Reproductive success of the re-laid native oyster Ostrea edulis in Chichester harbour. MSci Dissertation, University of Southampton, England. 2012."},{"issue":"4","key":"pone.0280777.ref037","doi-asserted-by":"crossref","first-page":"487","DOI":"10.3989\/scimar.04202.16A","article-title":"Seasonal variation in reproductive activity and biochemical composition of flat oyster (Ostrea edulis) in the Homa Lagoon, Izmir Bay, Turkey","volume":"79","author":"S Acarli","year":"2015","journal-title":"Sci Mar"},{"key":"pone.0280777.ref038","first-page":"38","article-title":"Gametogenesis, sex ratio and energy metabolism in Ostrea angasi: implications for the reproductive strategy of spermcasting marine bivalves","volume":"84","author":"M Hassan","year":"2018","journal-title":"Malacol Soc London J Molluscan Stud J Molluscan Stud"},{"key":"pone.0280777.ref039","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.aquaculture.2008.10.055","article-title":"Differences in gametogenic cycle among strains of the European flat oyster Ostrea edulis and relationship between gametogenesis and bonamiosis","volume":"287","author":"PM da Silva","year":"2009","journal-title":"Aquaculture"},{"issue":"2","key":"pone.0280777.ref040","doi-asserted-by":"crossref","first-page":"217","DOI":"10.2983\/035.030.0204","article-title":"Unusually High Proportion of Males in a Collapsing Population of Commercially Fished Oysters (Ostrea edulis) in the Solent, United Kingdom","volume":"30","author":"LM Kamphausen","year":"2011","journal-title":"J Shellfish Res"},{"issue":"12","key":"pone.0280777.ref041","doi-asserted-by":"crossref","first-page":"2643","DOI":"10.1007\/s00227-010-1525-2","article-title":"Population dynamics, sex ratio and size at sex change in a protandric simultaneous hermaphrodite, the spiny shrimp Exhippolysmata oplophoroides","volume":"157","author":"JA Baeza","year":"2010","journal-title":"Mar Biol"},{"key":"pone.0280777.ref042","first-page":"384","volume-title":"Stressors in the marine environment: physiological and ecological responses; societal implications","author":"C Lewis","year":"2016"},{"key":"pone.0280777.ref043","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1093\/oxfordjournals.mollus.a065097","article-title":"The occurrence of a penis-like outgrowth behind the right tentacle in spent females of Nucella lapillus (L.)","volume":"39","author":"SJM Blaber","year":"1970","journal-title":"J Molluscan Stud"},{"issue":"3","key":"pone.0280777.ref044","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1017\/S0025315400033208","article-title":"A Male genital defect in the dog-whelk, Nucella lapillus (Neogastropoda), favouring survival in a TBT-polluted area","volume":"73","author":"PE Gibbs","year":"1993","journal-title":"J Mar Biol Assoc United Kingdom"},{"issue":"3","key":"pone.0280777.ref045","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.cbpc.2007.11.007","article-title":"Endocrine-related reproductive effects in molluscs","volume":"147","author":"I Ketata","year":"2008","journal-title":"Comp. Biochem. Physiol. C Toxicol. Pharmacol"},{"issue":"1","key":"pone.0280777.ref046","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1002\/etc.5620170106","article-title":"Critical appraisal of the evidence for tributyltin-mediated endocrine disruption in mollusks","volume":"17","author":"P Matthiessen","year":"1998","journal-title":"Environ Toxicol Chem"},{"key":"pone.0280777.ref047","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/S0141-1136(02)00185-X","article-title":"Tributyltin and triphenyltin induce spermatogenesis in ovary of female abalone, Haliotis gigantea","volume":"54","author":"T Horiguchi","year":"2002","journal-title":"Mar Environ Res"},{"key":"pone.0280777.ref048","doi-asserted-by":"crossref","first-page":"193","DOI":"10.2166\/wst.1986.0195","article-title":"The Impact of Tributyl Tin (TBT) Antifouling Paints on Molluscan Fisheries","volume":"18","author":"JE Thain","year":"1986","journal-title":"Water Sci Technol"},{"key":"pone.0280777.ref049","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1109\/OCEANS.1987.1160659","volume-title":"OCEANS \u201887","author":"M Roberts","year":"1987"},{"key":"pone.0280777.ref050","doi-asserted-by":"crossref","first-page":"2694","DOI":"10.1093\/icesjms\/fsaa134","article-title":"Ostrea edulis beds in the central North Sea: delineation, ecology, and restoration","volume":"77","author":"FP Bennema","year":"2020","journal-title":"ICES J Mar Sci"},{"issue":"2","key":"pone.0280777.ref051","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.marpolbul.2014.03.029","article-title":"Magnetic characteristics of sediment grains concurrently contaminated with TBT and metals near a shipyard in Busan, Korea","volume":"85","author":"JY Choi","year":"2014","journal-title":"Mar Pollut Bull"},{"key":"pone.0280777.ref052","doi-asserted-by":"crossref","first-page":"135510","DOI":"10.1016\/j.scitotenv.2019.135510","article-title":"Integrated assessment of management strategies for metal-contaminated dredged sediments\u2013What are the best approaches for ports, marinas and waterways?","volume":"716","author":"A Nor\u00e9n","year":"2020","journal-title":"Sci Total Environ"},{"key":"pone.0280777.ref053","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.chemosphere.2014.07.008","article-title":"Significance of environmental dredging on metal mobility from contaminated sediments in the Oskarshamn Harbor, Sweden","volume":"119","author":"H Fathollahzadeh","year":"2015","journal-title":"Chemosphere"},{"issue":"1","key":"pone.0280777.ref054","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s42003-020-0957-6","article-title":"Anion-exchange chromatography mass spectrometry provides extensive coverage of primary metabolic pathways revealing altered metabolism in IDH1 mutant cells","volume":"3","author":"J Walsby-Tickle","year":"2020","journal-title":"Commun Biol"},{"key":"pone.0280777.ref055","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.scitotenv.2018.04.264","article-title":"Mussel digestive gland as a model tissue for assessing xenobiotics: An overview","volume":"636","author":"C Faggio","year":"2018","journal-title":"Sci Total Environ"},{"issue":"3","key":"pone.0280777.ref056","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1093\/icb\/icy017","article-title":"Mitochondrial adaptations to variable environments and their role in animals\u2019 stress tolerance","volume":"58","author":"I. Sokolova","year":"2018","journal-title":"Integr Comp Biol"},{"issue":"1","key":"pone.0280777.ref057","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.tiv.2010.10.001","article-title":"Tributyltin (TBT) and dibutyltin (DBT) differently inhibit the mitochondrial Mg-ATPase activity in mussel digestive gland","volume":"25","author":"S Nesci","year":"2011","journal-title":"Toxicol Vitr"},{"issue":"4","key":"pone.0280777.ref058","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.tiv.2007.12.015","article-title":"Tributyltin (TBT) inhibition of oligomycin-sensitive Mg-ATPase activity in mussel mitochondria","volume":"22","author":"A Pagliarani","year":"2008","journal-title":"Toxicol Vitr"},{"issue":"1","key":"pone.0280777.ref059","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.cbpc.2010.08.007","article-title":"Tributyltin inhibits the oligomycin-sensitive Mg-ATPase activity in Mytilus galloprovincialis digestive gland mitochondria","volume":"153","author":"V Ventrella","year":"2011","journal-title":"Comp Biochem Physiol\u2014C Toxicol Pharmacol"},{"issue":"3","key":"pone.0280777.ref060","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.biochi.2011.11.002","article-title":"Tributyltin-driven enhancement of the DCCD insensitive Mg-ATPase activity in mussel digestive gland mitochondria","volume":"94","author":"S Nesci","year":"2012","journal-title":"Biochimie"},{"issue":"1","key":"pone.0280777.ref061","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0014-5793(78)80510-9","article-title":"Fine control of the conversion of pyruvate (phosphoenolpyruvate) to oxaloacetate in various species","volume":"89","author":"MC Scrutton","year":"1978","journal-title":"FEBS Lett"},{"issue":"4","key":"pone.0280777.ref062","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.tiv.2011.03.004","article-title":"Tributyltin (TBT) and mitochondrial respiration in mussel digestive gland","volume":"25","author":"S Nesci","year":"2011","journal-title":"Toxicol Vitr"},{"key":"pone.0280777.ref063","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S0020-1693(02)01467-6","article-title":"Tributyltin and mitochondria: New evidence in support of an uncoupling mechanism and a further characterisation of the transport mechanism","volume":"348","author":"M Bragadin","year":"2003","journal-title":"Inorganica Chim Acta"},{"issue":"1","key":"pone.0280777.ref064","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1144\/gsjgs.140.1.0027","article-title":"Invertebrate and vertebrate pathways of anaerobic metabolism: evolutionary considerations","volume":"140","author":"DR Livingstone","year":"1983","journal-title":"J Geol Soc London"},{"key":"pone.0280777.ref065","doi-asserted-by":"crossref","first-page":"149","DOI":"10.2174\/978160805265311201010149","volume-title":"Biochemical and Biological Effects of Organotins","author":"Z. Jaksic","year":"2012"},{"issue":"5","key":"pone.0280777.ref066","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1023\/A:1009616228304","article-title":"Role of reactive oxygen species (ROS) in apoptosis induction","volume":"5","author":"H-U Simon","year":"2000","journal-title":"Apoptosis"},{"issue":"4","key":"pone.0280777.ref067","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: a review of programmed cell death","volume":"35","author":"S. Elmore","year":"2007","journal-title":"Toxicol Pathol"},{"key":"pone.0280777.ref068","doi-asserted-by":"crossref","unstructured":"Hongmei Z. Extrinsic and Intrinsic Apoptosis Signal Pathway Review. In: Apoptosis and Medicine. InTech; 2012. Available at: https:\/\/www.intechopen.com\/chapters\/38236 (Last accessed 30 June 2022).","DOI":"10.5772\/50129"},{"key":"pone.0280777.ref069","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/0141-1136(94)00031-J","article-title":"Glutathione peroxidase and other antioxidant enzyme function in marine invertebrates (Mytilus edulis, Pecten maximus, Carcinus maenas and Asterias rubens)","volume":"39","author":"SC Gamble","year":"1995","journal-title":"Mar Environ Res"},{"key":"pone.0280777.ref070","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3354\/meps046033","article-title":"Glutathione S-transferase in marine invertebrates from Langesundfjord","volume":"46","author":"RF Lee","year":"1988","journal-title":"Mar Ecol\u2014Prog Ser"},{"issue":"1","key":"pone.0280777.ref071","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1134\/S1063074011010056","article-title":"Glutathione S-transferase activity in marine invertebrates from Peter the Great Bay in the Sea of Japan","volume":"37","author":"NN Belcheva","year":"2011","journal-title":"Russ J Mar Biol"},{"issue":"8","key":"pone.0280777.ref072","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.neuint.2012.03.004","article-title":"Tributyltin induces oxidative stress and neuronal injury by inhibiting glutathione S-transferase in rat organotypic hippocampal slice cultures","volume":"60","author":"Y Ishihara","year":"2012","journal-title":"Neurochem Int"},{"issue":"3","key":"pone.0280777.ref073","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1007\/s10646-014-1416-2","article-title":"Responses of the hepatic glutathione antioxidant defense system and related gene expression in juvenile common carp after chronic treatment with tributyltin","volume":"24","author":"Z-H Li","year":"2015","journal-title":"Ecotoxicology"},{"issue":"3","key":"pone.0280777.ref074","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.ecoenv.2005.08.003","article-title":"Effects of tributyltin, benzo[a]pyrene, and their mixture on antioxidant defense systems in Sebastiscus marmoratus","volume":"65","author":"C Wang","year":"2006","journal-title":"Ecotoxicol Environ Saf"},{"issue":"12","key":"pone.0280777.ref075","first-page":"1","article-title":"Effects of antifouling biocides on molecular and biochemical defense system in the gill of the pacific oyster Crassostrea gigas","volume":"11","author":"MS Park","year":"2016","journal-title":"PLoS One"},{"issue":"4","key":"pone.0280777.ref076","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1095\/biolreprod.113.109728","article-title":"Sex-specific regulation of AMP-activated protein kinase (AMPK) in the pacific oyster Crassostrea gigas","volume":"89","author":"E Gu\u00e9v\u00e9lou","year":"2013","journal-title":"Biol Reprod"},{"issue":"5","key":"pone.0280777.ref077","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0155435","article-title":"The kinome of Pacific oyster Crassostrea gigas, its expression during development and in response to environmental factors","volume":"11","author":"Y Epelboin","year":"2016","journal-title":"PLoS One"},{"key":"pone.0280777.ref078","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.scitotenv.2015.01.065","article-title":"AMP-activated protein kinase is a biomarker of energetic status in freshwater mussels exposed to municipal effluents","author":"CG Goodchild","year":"2015","journal-title":"Sci Total Environ"},{"issue":"3","key":"pone.0280777.ref079","doi-asserted-by":"crossref","first-page":"459","DOI":"10.4067\/S0718-19572013000300005","article-title":"Relationship between energy allocation and gametogenesis in Aulacomya atra (Bivalvia: Mytilidae) in a sub-Antarctic environment","volume":"48","author":"AF P\u00e9rez","year":"2013","journal-title":"Rev Biol Mar Oceanogr"},{"key":"pone.0280777.ref080","doi-asserted-by":"crossref","first-page":"6271","DOI":"10.1021\/es049593u","article-title":"Involvement of the Retinoid X Receptor in the Development of Imposex Caused by Organotins in Gastropods","volume":"38","author":"JI Nishikawa","year":"2004","journal-title":"Environ Sci Tchnol"},{"issue":"4","key":"pone.0280777.ref081","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0176024","article-title":"Cloning retinoid and peroxisome proliferator-activated nuclear receptors of the Pacific oyster and in silico binding to environmental chemicals","volume":"12","author":"S Vogeler","year":"2017","journal-title":"PloS one"},{"issue":"1","key":"pone.0280777.ref082","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.aquatox.2007.07.016","article-title":"Imposex induction is mediated through the Retinoid X Receptor signalling pathway in the neogastropod Nucella lapillus","volume":"85","author":"LFC Castro","year":"2007","journal-title":"Aquat Toxicol"},{"issue":"9","key":"pone.0280777.ref083","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1210\/me.2005-0367","article-title":"Endocrine-disrupting organotin compounds are potent inducers of adipogenesis in vertebrates","volume":"20","author":"F Gr\u00fcn","year":"2006","journal-title":"Mol Endocrinol"},{"issue":"3","key":"pone.0280777.ref084","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.cbpc.2007.04.009","article-title":"Exposure to TBT increases accumulation of lipids and alters fatty acid homeostasis in the ramshorn snail Marisa cornuarietis","volume":"146","author":"G Janer","year":"2007","journal-title":"Comp Biochem Physiol C Toxicol Pharmacol"},{"issue":"3","key":"pone.0280777.ref085","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1016\/j.chemosphere.2012.10.078","article-title":"Tributyltin exposure causes lipotoxicity responses in the ovaries of rockfish, Sebastiscus marmoratus","volume":"90","author":"J Zhang","year":"2013","journal-title":"Chemosphere"},{"issue":"9","key":"pone.0280777.ref086","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1038\/sj.ki.5001834","article-title":"Lipotoxicity","volume":"70","author":"JM Weinberg","year":"2006","journal-title":"Kidney Int"},{"issue":"1","key":"pone.0280777.ref087","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cmet.2009.03.011","article-title":"As a Matter of Fat","volume":"10","author":"RT Brookheart","year":"2009","journal-title":"Cell Metab"},{"key":"pone.0280777.ref088","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.ecolind.2012.10.001","article-title":"Bivalve condition index as an indicator of aquaculture intensity: A meta-analysis","volume":"25","author":"R Filgueira","year":"2013","journal-title":"Ecol Indic"},{"key":"pone.0280777.ref089","unstructured":"Kim Y, Ashton-Alcox KA, Powell EN. Histological Techniques for Marine Bivalve Molluscs: Update. Silver Spring, MD. NOAA Technical Memorandum NOS NCCOS 27. Vol. 76. 2006."},{"key":"pone.0280777.ref090","unstructured":"Howard DW, Lewis EJ, Keller BJ, Smith CS. Histological techniques for marine bivalve mollusks and crustaceans, 2nd edition. 2004;218."},{"key":"pone.0280777.ref091","unstructured":"Wang C. Roles of Sex Steroids in reproduction of the Sea Scallop. Dalhousie University, Halifax, Nova Scotia; 2000. Available at: http:\/\/citeseerx.ist.psu.edu\/viewdoc\/download?doi=10.1.1.427.3208&rep=rep1&type=pdf (Last accessed 30 June 2022)."},{"issue":"8","key":"pone.0280777.ref092","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1046\/j.1365-2826.2003.01033.x","article-title":"Reproduction and resistance to stress: When and how","volume":"15","author":"JC Wingfield","year":"2003","journal-title":"J Neuroendocrinol"},{"issue":"3","key":"pone.0280777.ref093","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1890\/07-0605.1","article-title":"Intertidal Mussels Exhibit Energetic Trade-Offs between Reproduction and Stress Resistance","volume":"78","author":"LE Petes","year":"2008","journal-title":"Ecol Monogr"},{"issue":"2","key":"pone.0280777.ref094","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ygcen.2008.04.010","article-title":"Biological indices, energy reserves, steroid hormones and sexual maturity in the infaunal bivalve Scrobicularia plana from three sites differing by their level of contamination","volume":"157","author":"C Mouneyrac","year":"2008","journal-title":"Gen Comp Endocrinol"},{"issue":"12","key":"pone.0280777.ref095","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/0025-326X(87)90395-X","article-title":"Tin and organotin in water, sediments, and benthic organisms of Poole Harbour","volume":"18","author":"W. Langston","year":"1987","journal-title":"Mar Pollut Bull"},{"key":"pone.0280777.ref096","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0141-1136(95)00066-6","article-title":"Enhancement of Perkinsus marinus disease progression in TBT-exposed oysters (Crassostrea virginica)","volume":"42","author":"RS Anderson","year":"1996","journal-title":"Mar. Environ. Res"},{"key":"pone.0280777.ref097","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1017\/S0025315400027272","article-title":"The effects of tributyltin (TBT) accumulation on adult dog-whelks, Nucella lapillus: long-term field and laboratory experiments","volume":"67","author":"GW Bryan","year":"1987","journal-title":"J mar biol Ass UK"},{"key":"pone.0280777.ref098","doi-asserted-by":"crossref","first-page":"110523","DOI":"10.1016\/j.cbpa.2019.06.023","article-title":"Effects of the interaction between temperature and steroid hormones on gametogenesis and sex ratio in the European flat oyster (Ostrea edulis)","volume":"236","author":"LM Zapata-Restrepo","year":"2019","journal-title":"Comp Biochem Physiol -Part A Mol Integr Physiol"},{"issue":"4","key":"pone.0280777.ref099","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/0044-8486(76)90119-8","article-title":"Experiments on the culture in the sea of the butterfish Venerupis decussata L","volume":"8","author":"PR Walne","year":"1976","journal-title":"Aquaculture"},{"issue":"1","key":"pone.0280777.ref100","doi-asserted-by":"crossref","first-page":"23","DOI":"10.2307\/1352213","article-title":"The Determination and Use of Condition Index of Oysters","volume":"5","author":"DR Lawrence","year":"1982","journal-title":"Estuaries"},{"issue":"3","key":"pone.0280777.ref101","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1086\/399023","article-title":"Recent Advances in Oyster Biology","volume":"27","author":"P. Korringa","year":"1952","journal-title":"Q Rev Biol"},{"key":"pone.0280777.ref102","first-page":"1","article-title":"Studies of the biology of the oyster (Ostrea edulis) in Limfjord, with special reference to the influence of temperature and the sex-change","volume":"30","author":"R. Sparck","year":"1925","journal-title":"Rep Dan Biol Sta"},{"issue":"1962","key":"pone.0280777.ref103","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1126\/science.76.1962.125.c","article-title":"Histological basis of sex changes in the american oyster (Ostrea virginica)","volume":"76","author":"WR Coe","year":"1932","journal-title":"Science (80-)"},{"issue":"1","key":"pone.0280777.ref104","doi-asserted-by":"crossref","first-page":"86","DOI":"10.2307\/1539324","article-title":"Gametogenesis and spawning of the European oyster, O. edulis, in waters of Maine","volume":"122","author":"VL Loosanoff","year":"1962","journal-title":"Biol Bull"},{"issue":"8","key":"pone.0280777.ref105","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1139\/o59-099","article-title":"A rapid method of total lipid extraction and purification","volume":"37","author":"EG Bligh","year":"1959","journal-title":"Can J Biochem Physiol"},{"issue":"3","key":"pone.0280777.ref106","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/0022-0981(85)90159-5","article-title":"Physiological and biochemical energetics of larvae of Teredo navalis L. and Bankia gouldi (Bartsch) (Bivalvia: Teredinidae)","volume":"85","author":"R Mann","year":"1985","journal-title":"J Exp Mar Bio Ecol"},{"issue":"3","key":"pone.0280777.ref107","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1093\/icesjms\/28.3.354","article-title":"Biochemical Studies on Marine Zooplankton: I. The Biochemical Composition of Neomysis integer","volume":"28","author":"JEG Raymont","year":"1964","journal-title":"ICES J Mar Sci"},{"key":"pone.0280777.ref108","volume-title":"Amino Acid Analysis Methods in Molecular Biology (Methods and Protocols)","author":"C Salazar","year":"2012"}],"updated-by":[{"DOI":"10.1371\/journal.pone.0341792","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000}}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0280777","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T21:42:52Z","timestamp":1768340572000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0280777"}},"subtitle":[],"editor":[{"given":"Michael","family":"Schubert","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,2,6]]},"references-count":108,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0280777","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,6]]}}}