{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:59:41Z","timestamp":1762869581768,"version":"build-2065373602"},"reference-count":87,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UIDB\/04423\/2020","UIDP\/04423\/2020"],"award-info":[{"award-number":["UIDB\/04423\/2020","UIDP\/04423\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Animals"],"abstract":"<jats:p>Global warming raises surface water temperatures, impacting fish alongside pollutants, such as ubiquitous xenoestrogens. Combined stressor effects are poorly studied but likely to worsen impacts and hinder biota adaptation, warranting further research. Unadapted fish face heightened risks. The liver is a vital metabolic organ, sensitive to temperature and xenoestrogens, eventually adjusting hepatocyte size and number to ensure survival, growth, and reproduction. This study assessed, for the first time, the impact of exposure (45 days) to thermal stress (29 \u00b0C versus 26 \u00b0C) and ethinylestradiol (EE2, 5 ng\/L) on male guppies, primarily on body and quantitative liver morphology. Higher temperature reduced body mass (14%) and standard length (3.6%) gain. EE2 exposure reduced body mass increase (14%), hepatosomatic index (20%), and the volumes of the liver (32%), hepatocytes (16%), and their nuclei (17%). The nucleus-to-cytoplasm ratio and total hepatocyte number remained stable. No histopathological lesions existed. Guppies appear to have adapted to stressors by reducing hepatocyte size and utilizing lipid reserves, yet they exhibited deficits in body growth and hepatosomatic index. Gonadal maturation was unaffected. Only under EE2 at 29 \u00b0C did hepatocytes show minimal lipid droplet content (less vacuolation). This indicated exhausted reserves, reinforcing how heat and toxicants interact to exacerbate impacts.<\/jats:p>","DOI":"10.3390\/ani15142152","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T13:59:11Z","timestamp":1753106351000},"page":"2152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["High Temperature and Ethinylestradiol May Reduce Body Growth, Liver and Hepatocyte Volumes and Lipid Droplets in Adult Male Guppies"],"prefix":"10.3390","volume":"15","author":[{"given":"Margarida","family":"Vila\u00e7a","sequence":"first","affiliation":[{"name":"Laboratory of Histology and Embryology, Department of Microscopy, School of Medicine and Biomedical Sciences (ICBAS), University of Porto (U. Porto), 4050-313 Porto, Portugal"},{"name":"Group of Animal Morphology and Toxicology, Interdisciplinary Centre for Marine and Environmental Research (CIIMAR\/CIMAR), University of Porto (U. Porto), 4450-208 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5538-6690","authenticated-orcid":false,"given":"Sukanlaya","family":"Tantiwisawaruji","sequence":"additional","affiliation":[{"name":"Group of Animal Morphology and Toxicology, Interdisciplinary Centre for Marine and Environmental Research (CIIMAR\/CIMAR), University of Porto (U. Porto), 4450-208 Porto, Portugal"},{"name":"Learning Institute, King Mongkut\u2019s University of Technology Thonburi, Bangkok 10140, Thailand"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8688-8033","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Rocha","sequence":"additional","affiliation":[{"name":"Laboratory of Histology and Embryology, Department of Microscopy, School of Medicine and Biomedical Sciences (ICBAS), University of Porto (U. Porto), 4050-313 Porto, Portugal"},{"name":"Group of Animal Morphology and Toxicology, Interdisciplinary Centre for Marine and Environmental Research (CIIMAR\/CIMAR), University of Porto (U. Porto), 4450-208 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9813-4389","authenticated-orcid":false,"given":"Eduardo","family":"Rocha","sequence":"additional","affiliation":[{"name":"Laboratory of Histology and Embryology, Department of Microscopy, School of Medicine and Biomedical Sciences (ICBAS), University of Porto (U. Porto), 4050-313 Porto, Portugal"},{"name":"Group of Animal Morphology and Toxicology, Interdisciplinary Centre for Marine and Environmental Research (CIIMAR\/CIMAR), University of Porto (U. Porto), 4450-208 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gabric, A.J. (2023). The Climate Change Crisis: A review of its causes and possible responses. Atmosphere, 14.","DOI":"10.3390\/atmos14071081"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s11160-007-9059-5","article-title":"Potential impacts of global climate change on freshwater fisheries","volume":"17","author":"Ficke","year":"2007","journal-title":"Rev. Fish Biol. Fish."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e2201345119","DOI":"10.1073\/pnas.2201345119","article-title":"Impact of warming on aquatic body sizes explained by metabolic scaling from microbes to macrofauna","volume":"119","author":"Deutsch","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/nclimate1084","article-title":"Tolerance limit for fish growth exceeded by warming waters","volume":"1","author":"Neuheimer","year":"2011","journal-title":"Nat. Clim. Change"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/jfb.14402","article-title":"What do warming waters mean for fish physiology and fisheries?","volume":"97","author":"Little","year":"2020","journal-title":"J. Fish Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1126\/science.1137359","article-title":"The heartbreak of adapting to global warming","volume":"315","author":"Wang","year":"2007","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1152\/physiol.00027.2022","article-title":"Physiological mechanisms of acute upper thermal tolerance in fish","volume":"38","author":"Ern","year":"2023","journal-title":"Physiology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1098\/rstb.2010.0055","article-title":"Climate change and freshwater ecosystems: Impacts across multiple levels of organization","volume":"365","author":"Woodward","year":"2010","journal-title":"Philos. Trans. R. Soc. B"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Basova, M., Krasheninnikova, S., and Parrino, V. (2022). Intra-decadal (2012\u20132021) dynamics of spatial ichthyoplankton distribution in sevastopol bay (Black Sea) affected by hydrometeorological factors. Animals, 12.","DOI":"10.3390\/ani12233317"},{"key":"ref_10","unstructured":"Letcher, T.M. (2021). Chapter 8: Effects of Climate Change on Food Production (Fishing). The Impacts of Climate Change: A Comprehensive Study of Physical, Biophysical, Social and Political Issues, Elsevier."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"106719","DOI":"10.1016\/j.ocecoaman.2023.106719","article-title":"A systematic literature review of climate change research on Europe\u2019s threatened commercial fish species","volume":"242","author":"Predragovic","year":"2023","journal-title":"Ocean Coast. Manag."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.fsi.2016.03.018","article-title":"The effect of hyperthermia on liver histology, oxidative stress and disease resistance of the Wuchang bream, Megalobrama amblycephala","volume":"52","author":"Liu","year":"2016","journal-title":"Fish Shellfish. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Nuez-Ort\u00edn, W.G., Carter, C.G., Nichols, P.D., Cooke, I.R., and Wilson, R. (2018). Liver proteome response of pre-harvest Atlantic salmon following exposure to elevated temperature. BMC Genom., 19.","DOI":"10.1186\/s12864-018-4517-0"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1080\/24750263.2018.1460694","article-title":"Comparative study of haematology of two teleost fish (Mugil cephalus and Carassius auratus) from different environments and feeding habits","volume":"85","author":"Parrino","year":"2018","journal-title":"Eur. Zool. J."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Pironti, C., Ricciardi, M., Proto, A., Bianco, P.M., Montano, L., and Motta, O. (2021). Endocrine-disrupting compounds: An overview on their occurrence in the aquatic environment and human exposure. Water, 13.","DOI":"10.3390\/w13101347"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Rocha, M.J., and Rocha, E. (2015). Estrogenic Compounds in Estuarine and Coastal Water Environments of the Iberian Western Atlantic Coast and Selected Locations Worldwide\u2014Relevancy, Trends and Challenges in View of the EU Water Framework Directive. Toxicology Studies\u2014Cells, Drugs and Environment, In Tech.","DOI":"10.5772\/59885"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1210\/er.2009-0002","article-title":"Endocrine-disrupting chemicals: An Endocrine Society scientific statement","volume":"30","author":"Bourguignon","year":"2009","journal-title":"Endocr. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"112658","DOI":"10.1016\/j.envres.2021.112658","article-title":"An introduction to the sources, fate, occurrence and effects of endocrine disrupting chemicals released into the environment","volume":"207","author":"Metcalfe","year":"2022","journal-title":"Environ. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lauretta, R., Sansone, A., Sansone, M., Romanelli, F., and Appetecchia, M. (2019). Endocrine disrupting chemicals: Effects on endocrine glands. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00178"},{"key":"ref_20","unstructured":"National Center for Biotechnology Information (2025, April 04). PubChem Compound Summary for CID 5991, Ethinyl Estradiol, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Ethinyl-estradiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"112804","DOI":"10.1016\/j.jenvman.2021.112804","article-title":"A review of 17\u03b1-ethynylestradiol (EE2) in surface water across 32 countries: Sources, concentrations, and potential estrogenic","volume":"292","author":"Tang","year":"2021","journal-title":"J. Environ. Manag."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1476-5926-2-4","article-title":"Eggshell and egg yolk proteins in fish: Hepatic proteins for the next generation: Oogenetic, population, and evolutionary implications of endocrine disruption","volume":"2","author":"Arukwe","year":"2003","journal-title":"Comp. Hepatol."},{"key":"ref_23","first-page":"45","article-title":"Effects of octylphenol and 17\u03b2-estradiol on the gonads of guppies (Poecilia reticulata) exposed as adults via the water or as embryos via the mother","volume":"134","author":"Kinnberg","year":"2003","journal-title":"Comp. Biochem. Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.aquatox.2005.10.015","article-title":"17Beta-estradiol induced compositional, structural and functional changes in rainbow trout liver, revealed by FT-IR spectroscopy: A comparative study with nonylphenol","volume":"77","author":"Cakmak","year":"2006","journal-title":"Aquat. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"101327","DOI":"10.1016\/j.tice.2019.101327","article-title":"Histology and design-based estimation of hepatocellularity and volumes of hepatocytes in control and ethynylestradiol exposed males of platyfish (Xiphophorus maculatus)","volume":"63","author":"Real","year":"2020","journal-title":"Tissue Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1053\/j.gastro.2019.01.010","article-title":"Estrogen activation of G-protein\u2013coupled estrogen receptor 1 regulates phosphoinositide 3-kinase and mTOR signaling to promote liver growth in zebrafish and proliferation of human hepatocytes","volume":"156","author":"Chaturantabut","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1093\/carcin\/13.12.2381","article-title":"Ethinyl estradiol-induced cell proliferation in rat liver. Involvement of specific populations of hepatocytes","volume":"13","author":"Mayol","year":"1992","journal-title":"Carcinogenesis"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"DeCourten, B.M., and Brander, S.M. (2017). Combined effects of increased temperature and endocrine disrupting pollutants on sex determination, survival, and development across generations. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-09631-1"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.envpol.2017.05.090","article-title":"Warming modulates the effects of the endocrine disruptor progestin levonorgestrel on the zebrafish fitness, ovary maturation kinetics and reproduction success","volume":"229","author":"Cardoso","year":"2017","journal-title":"Environ. Pollut."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.ecoenv.2019.01.085","article-title":"High temperature aggravates the effects of pesticides in goldfish","volume":"172","author":"Jacquin","year":"2019","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1016\/j.scitotenv.2017.10.069","article-title":"Temperature modulates estrone degradation and biological effects of exposure in fathead minnows","volume":"621","author":"Cox","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"121558","DOI":"10.1007\/s11356-023-30794-0","article-title":"The impacts of synthetic and cellulose-based fibres and their associated dyes on fish hosts and parasite health","volume":"58","author":"MacAulay","year":"2023","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/jps.2600560242","article-title":"Absorption of ethanol by the Common guppy (Lebistes reticulatus)","volume":"56","author":"Hall","year":"1967","journal-title":"J. Pharm. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"418","DOI":"10.4254\/wjh.v9.i8.418","article-title":"Chronic exposure to ethanol causes steatosis and inflammation in zebrafish liver","volume":"9","author":"Schneider","year":"2017","journal-title":"World J. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Park, K., and Kim, S. (2019). Low dose of chronic ethanol exposure in adult zebrafish induces hepatic steatosis and injury. Biomed. Pharmacother., 117.","DOI":"10.1016\/j.biopha.2019.109179"},{"key":"ref_36","first-page":"1","article-title":"Computation and interpretation of biological statistics of fish populations","volume":"191","author":"Ricker","year":"1975","journal-title":"Bull. Fish. Res. Board Can."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/jat.1468","article-title":"Long-term exposure to bis(2-ethylhexyl)phthalate (DEHP) inhibits growth of guppy fish (Poecilia reticulata)","volume":"30","author":"Zanotelli","year":"2010","journal-title":"J. Appl. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s10228-012-0302-2","article-title":"Variations in the volumes of parenchyma and stroma of the liver and in the cytology of hepatocytes are associated with gonadal stages in female Ohrid trout (Salmo letnica)","volume":"60","author":"Jordanova","year":"2013","journal-title":"Ichthyol. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1080\/01478885.2015.1106072","article-title":"Osmium tetroxide post-fixation and periodic acid-Schiff dual-staining technique to demonstrate intracellular lipid and glycogen in the mouse liver section\u2014A novel method for co-visualization of intracellular contents in paraffin-embedded tissue","volume":"39","author":"Gates","year":"2016","journal-title":"J. Histotechnol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Louren\u00e7o, T., Rocha, E., Gon\u00e7alves, J.F., Rocha, M.J., and Madureira, T.V. (2024). A proof-of-concept for a hypolipidemic brown trout model. Toxics, 12.","DOI":"10.3390\/toxics12030219"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1365-2818.1986.tb02764.x","article-title":"Stereology of arbitrary particles. A review of unbiased number and size estimators and the presentation of some new ones, in memory of William R","volume":"143","author":"Gundersen","year":"1986","journal-title":"Thompson. J. Microsc."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1365-2818.1988.tb04609.x","article-title":"The nucleator","volume":"151","author":"Gundersen","year":"1988","journal-title":"J. Microsc."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1111\/j.1699-0463.1988.tb00954.x","article-title":"The new stereological tools: Disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis","volume":"96","author":"Gundersen","year":"1988","journal-title":"APMIS"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1111\/j.1478-3231.2005.01201.x","article-title":"Design-based stereological estimation of hepatocyte number, by combining the smooth optical fractionator and immunocytochemistry with anti-carcinoembryonic antigen polyclonal antibodies","volume":"26","author":"Marcos","year":"2006","journal-title":"Liver Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/j.1365-2818.1984.tb02501.x","article-title":"The unbiased estimation of number and sizes of arbitrary particles using the disector","volume":"134","author":"Sterio","year":"1983","journal-title":"J. Microsc."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/j.1365-2818.1977.tb00062.x","article-title":"Notes on the estimation of the numerical density of arbitrary profiles: The edge effect","volume":"111","author":"Gundersen","year":"1977","journal-title":"J. Microsc."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1095\/biolreprod65.5.1383","article-title":"Stereologic characterization of bovine (Bos taurus) cumulus-oocyte complexes aspirated from small antral follicles during the diestrous phase 1","volume":"65","author":"Calado","year":"2001","journal-title":"Biol. Reprod."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1002\/jemt.23228","article-title":"Estimating volumes from common carp hepatocytes using design-based stereology and examining correlations with profile areas: Revisiting a nutritional assay and unveiling guidelines to microscopists","volume":"82","author":"Cruzeiro","year":"2019","journal-title":"Microsc. Res. Tech."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/j.1365-2818.1987.tb02837.x","article-title":"The efficiency of systematic sampling in stereology and its prediction","volume":"147","author":"Gundersen","year":"1987","journal-title":"J. Microsc."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1083\/jcb.30.1.23","article-title":"Practical stereological methods for morphometric cytology","volume":"30","author":"Weibel","year":"1966","journal-title":"J. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1007\/s00411-014-0546-5","article-title":"Monte Carlo derived absorbed fractions for a voxelized model of Oncorhynchus mykiss, a rainbow trout","volume":"53","author":"Ruedig","year":"2014","journal-title":"Radiat. Environ. Biophys."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13244-023-01431-8","article-title":"CT volume analysis in living donor liver transplantation: Accuracy of three different approaches","volume":"14","author":"Kalshabay","year":"2023","journal-title":"Insights Imaging"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1080\/03067319.2010.496043","article-title":"Development and Optimisation of a GC-MS Method for the Evaluation of Oestrogens and Persistent Pollutants in River and Seawater Samples","volume":"91","author":"Rocha","year":"2011","journal-title":"Int. J. Environ. Anal. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1080\/02772248.2013.773002","article-title":"Quantification of 17 endocrine disruptor compounds and their spatial and seasonal distribution in the Iberian Ave River and its coastline","volume":"95","author":"Rocha","year":"2013","journal-title":"Toxicol. Environ. Chem."},{"key":"ref_55","unstructured":"Core Writing Team, Lee, H., and Romero, J. (2023). Climate Change 2023: Synthesis Report. Contribution of Working Groups I, II and III to the Sixth Assessment Report of the Intergovernmental Panel on Climate Change, IPCC."},{"key":"ref_56","unstructured":"Baerends, G., Beer, P., and Manning, C. (1975). Factors Affecting the Morphology and Behaviour of Guppies in Trinidad. Function and Evolution in Behaviour: Essays in Honour of Professor Niko Tinbergen, Oxford Univ. Press."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1111\/jfb.14599","article-title":"Temperature increase and its effects on fish stress physiology in the context of global warming","volume":"98","author":"Alfonso","year":"2021","journal-title":"J. Fish Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1007\/s00300-020-02752-w","article-title":"Thermal sensitivity of cell metabolism of different Antarctic fish species mirrors organism temperature tolerance","volume":"43","author":"Lannig","year":"2020","journal-title":"Polar Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.domaniend.2016.01.001","article-title":"Effects of steroid treatment on growth, nutrient partitioning, and expression of genes related to growth and nutrient metabolism in adult triploid rainbow trout (Oncorhynchus mykiss)","volume":"56","author":"Cleveland","year":"2016","journal-title":"Domest. Anim. Endocrinol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1002\/tox.20012","article-title":"Xenoestrogenic effects of ethinylestradiol in zebrafish (Danio rerio)","volume":"19","author":"Versonnen","year":"2004","journal-title":"Environ. Toxicol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Mo, N., Zhang, M., Wang, R., Xia, S., Meng, F., Qian, Y., and Li, M. (2019). Effects of \u03b1-ethinyl estradiol (EE2) and diethylhexyl phthalate (DEHP) on growth performance, antioxidant status and immune response of juvenile yellow catfish Pelteobagrus fulvidraco. Comp. Biochem. Physiol. C Toxicol. Pharmacol., 226.","DOI":"10.1016\/j.cbpc.2019.108615"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1080\/01926230590890187","article-title":"A brief overview of nonneoplastic hepatic toxicity in fish","volume":"33","author":"Wolf","year":"2005","journal-title":"Toxicol. Pathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.aquatox.2018.01.013","article-title":"A critical review of histopathological findings associated with endocrine and non-endocrine hepatic toxicity in fish models","volume":"197","author":"Wolf","year":"2018","journal-title":"Aquat. Toxicol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.tice.2017.12.009","article-title":"Characterization and spatial relationships of the hepatic vascular\u2013biliary tracts, and their associated pancreocytes and macrophages, in the model fish guppy (Poecilia reticulata): A study of serial sections by light microscopy","volume":"50","author":"Sousa","year":"2018","journal-title":"Tissue Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"294278","DOI":"10.1155\/2015\/294278","article-title":"Sex hormones and their receptors regulate liver energy homeostasis","volume":"2015","author":"Shen","year":"2015","journal-title":"Int. J. Endocrinol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Zhao, T., Ma, A., Huang, Z., Liu, Z., Sun, Z., Zhu, C., Yang, J., Li, Y., Wang, Q., and Qiao, X. (2021). Transcriptome analysis reveals that high temperatures alter modes of lipid metabolism in juvenile turbot (Scophthalmus maximus) liver. Comp. Biochem. Physiol. D Genom. Proteom., 40.","DOI":"10.1016\/j.cbd.2021.100887"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1086\/physzool.65.5.30158547","article-title":"Alterations in liver composition of channel catfish (Ictalurus punctatus) during seasonal acclimatization","volume":"65","author":"Kent","year":"1992","journal-title":"Physiol. Zool."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12302-020-00316-7","article-title":"Fish biomarkers from a different perspective: Evidence of adaptive strategy of Abramis brama (L.) to chemical stress","volume":"32","author":"Tenji","year":"2020","journal-title":"Environ. Sci. Eur."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Orso, G., Imperatore, R., Coccia, E., Rinaldi, G., Cicchella, D., and Paolucci, M. (2023). A deep survey of fish health for the recognition of useful biomarkers to monitor water pollution. Environments, 10.","DOI":"10.20944\/preprints202311.0561.v1"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.1897\/05-565R.1","article-title":"Dynamics of 17alpha-ethynylestradiol exposure in rainbow trout (Oncorhynchus mykiss): Absorption, tissue distribution, and hepatic gene expression pattern","volume":"25","author":"Skillman","year":"2006","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"100382","DOI":"10.1016\/j.aqrep.2020.100382","article-title":"Effects of waterborne exposure to 17\u03b2-estradiol on hepatic lipid metabolism genes in tilapia (Oreochromis niloticus)","volume":"17","author":"Zhang","year":"2020","journal-title":"Aquac. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"R389","DOI":"10.1152\/ajpregu.2000.279.2.R389","article-title":"Effect of 17\u03b2-estradiol on the expression of somatostatin genes in rainbow trout (Oncorhynchus mykiss)","volume":"279","author":"Holloway","year":"2000","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1002\/etc.5620220613","article-title":"Short-term exposure to 17 alpha-ethynylestradiol decreases the fertility of sexually maturing male rainbow trout (Oncorhynchus mykiss)","volume":"22","author":"Schultz","year":"2003","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"R527","DOI":"10.1152\/ajpregu.2001.280.2.R527","article-title":"Effects of 17 beta-estradiol on levels and distribution of metallothionein and zinc in squirrelfish","volume":"280","author":"Thompson","year":"2001","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1080\/01926230252824699","article-title":"Alteration of liver cell function and proliferation: Differentiation between adaptation and toxicity","volume":"30","author":"Williams","year":"2002","journal-title":"Toxicol. Pathol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/jmor.10396","article-title":"Temperature and gender influences on the hepatic stroma (and associated pancreatic acini) of Nile tilapia, Oreochromis niloticus (Teleostei, Cichlidae): A stereological analysis by light microscopy","volume":"267","author":"Monteiro","year":"2006","journal-title":"J. Morphol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1152\/physrev.00061.2009","article-title":"Hepatocyte death: A clear and present danger","volume":"90","author":"Malhi","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1002\/lsm.22231","article-title":"Heat stress induced cell death mechanisms in hepatocytes and hepatocellular carcinoma: In vitro and in vivo study","volume":"46","author":"Thompson","year":"2014","journal-title":"Lasers Surg. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/978-1-4899-8032-8_25","article-title":"Mechanisms of nuclear size regulation in model systems and cancer","volume":"773","author":"Levy","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_80","unstructured":"Lanza, R., and Atala, A. (2013). Cell\u2013ECM Interactions in Repair and Regeneration. Handbook of Stem Cells, Academic Press. [2nd ed.]."},{"key":"ref_81","first-page":"310","article-title":"Fasting reduces hepatocyte size in the rat liver","volume":"145","author":"Nieminen","year":"2006","journal-title":"Comp. Biochem. Physiol. A Mol. Integr. Physiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1053\/jhep.2001.24750","article-title":"Liver cell volume regulation: Size matters","volume":"33","author":"Dunkelberg","year":"2001","journal-title":"Hepatology"},{"key":"ref_83","first-page":"1213","article-title":"Nucleocytoplasmic ratios in different populations of rat liver parenchymal cells during azo dye carcinogenesis","volume":"25","author":"Molnar","year":"1965","journal-title":"Cancer Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1146\/annurev-genet-080320-030537","article-title":"The nuclear-to-cytoplasmic ratio: Coupling DNA content to cell size, cell cycle, and biosynthetic capacity","volume":"56","author":"Balachandra","year":"2022","journal-title":"Annu. Rev. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1002\/ags3.12658","article-title":"Long-term risk of a fatty liver in liver donors","volume":"7","author":"Goto","year":"2023","journal-title":"Ann. Gastroenterol. Surg."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/S0147-6513(02)00010-6","article-title":"Effects of estrogenic and antiandrogenic compounds on the testis structure of the adult guppy (Poecilia reticulata)","volume":"54","author":"Kinnberg","year":"2003","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.aquatox.2006.08.004","article-title":"Quantitative studies on the effects of environmental estrogens on the testis of the guppy, Poecilia reticulata","volume":"80","author":"Nielsen","year":"2006","journal-title":"Aquat. Toxicol."}],"container-title":["Animals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2615\/15\/14\/2152\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:13:19Z","timestamp":1760033599000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2615\/15\/14\/2152"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,21]]},"references-count":87,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["ani15142152"],"URL":"https:\/\/doi.org\/10.3390\/ani15142152","relation":{},"ISSN":["2076-2615"],"issn-type":[{"type":"electronic","value":"2076-2615"}],"subject":[],"published":{"date-parts":[[2025,7,21]]}}}