{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T02:49:47Z","timestamp":1782960587477,"version":"3.54.5"},"reference-count":71,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoX"],"abstract":"<jats:p>With the legalization of marijuana smoking in several states of the United States and many other countries for medicinal and recreational use, the possibility of its release into the environment cannot be overruled. Currently, the environmental levels of marijuana metabolites are not monitored on a regular basis, and their stability in the environment is not well understood. Laboratory studies have linked delta 9-tetrahydrocannabinol (\u03949-THC) exposure with behavioral abnormalities in some fish species; however, their effects on endocrine organs are less understood. To understand the effects of THC on the brain and gonads, we exposed adult medaka (Oryzias latipes, Hd-rR strain, both male and female) to 50 ug\/L THC for 21 days spanning their complete spermatogenic and oogenic cycles. We examined transcriptional responses of the brain and gonads (testis and ovary) to \u03949-THC, particularly molecular pathways associated with behavioral and reproductive functions. The \u03949-THC effects were more profound in males than females. The \u03949-THC-induced differential expression pattern of genes in the brain of the male fish suggested pathways to neurodegenerative diseases and pathways to reproductive impairment in the testis. The present results provide insights into endocrine disruption in aquatic organisms due to environmental cannabinoid compounds.<\/jats:p>","DOI":"10.3390\/jox13020018","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T03:02:23Z","timestamp":1685415743000},"page":"237-251","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Transcriptional Alterations Induced by Delta-9 Tetrahydrocannabinol in the Brain and Gonads of Adult Medaka"],"prefix":"10.3390","volume":"13","author":[{"given":"Marlee","family":"Vassall","sequence":"first","affiliation":[{"name":"Department of Biology, University of North Carolina, Greensboro, NC 27412, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sourav","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Biology, University of North Carolina, Greensboro, NC 27412, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yashi","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Biology, University of North Carolina, Greensboro, NC 27412, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehwish","family":"Faheem","sequence":"additional","affiliation":[{"name":"Department of Biology, University of North Carolina, Greensboro, NC 27412, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4159-5402","authenticated-orcid":false,"given":"Xuegeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biology, University of North Carolina, Greensboro, NC 27412, USA"},{"name":"Institute of Modern Aquaculture Science and Engineering, College of Life Sciences, South China Normal University, Guangzhou 510631, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5608-7254","authenticated-orcid":false,"given":"Ramji Kumar","family":"Bhandari","sequence":"additional","affiliation":[{"name":"Department of Biology, University of North Carolina, Greensboro, NC 27412, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41585-020-00391-8","article-title":"Cannabinoid signaling and effects of cannabis on the male reproductive system","volume":"18","author":"Maccarrone","year":"2021","journal-title":"Nat. Rev. Urol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1111\/j.1476-5381.2010.01176.x","article-title":"Regulation of nausea and vomiting by cannabinoids","volume":"163","author":"Parker","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1310","DOI":"10.1542\/peds.2015-1807","article-title":"Incidence of Dravet Syndrome in a US Population","volume":"136","author":"Wu","year":"2015","journal-title":"Pediatrics"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Yu, B., Chen, X., Chen, X., and Yan, H. (2020). Marijuana legalization and historical trends in marijuana use among US residents aged 12\u201325: Results from the 1979\u20132016 National Survey on drug use and health. BMC Public Health, 20.","DOI":"10.1186\/s12889-020-8253-4"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.cofs.2019.02.010","article-title":"The imperatives and challenges of analyzing Cannabis edibles","volume":"28","author":"Leghissa","year":"2019","journal-title":"Curr. Opin. Food Sci."},{"key":"ref_6","first-page":"99","article-title":"The role of the endocannabinoid system in the regulation of endocrine function and in the control of energy balance in humans","volume":"61","author":"Komorowski","year":"2007","journal-title":"Postep. Hig. I Med. Dosw."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0009-3084(00)00195-X","article-title":"Cannabinoid receptors and the regulation of immune response","volume":"108","author":"Berdyshev","year":"2000","journal-title":"Chem. Phys. Lipids"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/35102582","article-title":"An anorexic lipid mediator regulated by feeding","volume":"414","author":"Navarro","year":"2001","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2708","DOI":"10.1523\/JNEUROSCI.5404-03.2004","article-title":"Expression of cannabinoid CB1 receptors by vagal afferent neurons is inhibited by cholecystokinin","volume":"24","author":"Burdyga","year":"2004","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1530\/eje.0.1470255","article-title":"Evidence for functional CB1 cannabinoid receptor expressed in the rat thyroid","volume":"147","author":"Porcella","year":"2002","journal-title":"Eur. J. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.ajog.2003.07.013","article-title":"Cannabinoids and the human uterus during pregnancy","volume":"190","author":"Dennedy","year":"2004","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/apha.12474","article-title":"Effects of pro-inflammatory cytokines on cannabinoid CB 1 and CB 2 receptors in immune cells","volume":"214","author":"Braitch","year":"2015","journal-title":"Acta Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1006\/taap.1996.8034","article-title":"Cannabinoid receptors CB1 and CB2: A characterization of expression and adenylate cyclase modulation within the immune system","volume":"142","author":"Schatz","year":"1997","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.bbalip.2018.02.001","article-title":"\u0394(9)-Tetrahydrocannabinol changes the brain lipidome and transcriptome differentially in the adolescent and the adult","volume":"1863","author":"Leishman","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/s41380-018-0243-x","article-title":"Adolescent exposure to \u03949-tetrahydrocannabinol alters the transcriptional trajectory and dendritic architecture of prefrontal pyramidal neurons","volume":"24","author":"Miller","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"361","DOI":"10.3389\/fnins.2014.00361","article-title":"Long-term consequences of adolescent cannabinoid exposure in adult psychopathology","volume":"8","author":"Renard","year":"2014","journal-title":"Front. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"15460","DOI":"10.1074\/jbc.M116.719179","article-title":"RNA-seq analysis of \u03b49-tetrahydrocannabinol-treated T cells reveals altered gene expression profiles that regulate immune response and cell proliferation","volume":"291","author":"Yang","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_18","first-page":"79","article-title":"Cytochrome P-450 isozymes involved in the oxidative metabolism of delta 9-tetrahydrocannabinol by liver microsomes of adult female rats","volume":"20","author":"Narimatsu","year":"1992","journal-title":"Drug Metab. Dispos."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/sj.ijo.0802250","article-title":"Endogenous cannabinoid system as a modulator of food intake","volume":"27","author":"Cota","year":"2003","journal-title":"Int. J. Obes."},{"key":"ref_20","first-page":"1011","article-title":"Involvement of the Cannabinoid System in the Regulation of Food Intake","volume":"14","author":"Rutkowska","year":"2005","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_21","first-page":"862","article-title":"Marihuana smoking suppresses luteinizing hormone in women","volume":"237","author":"Mendelson","year":"1986","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7678","DOI":"10.1073\/pnas.91.16.7678","article-title":"Anandamide (arachidonylethanolamide), a brain cannabinoid receptor agonist, reduces sperm fertilizing capacity in sea urchins by inhibiting the acrosome reaction","volume":"91","author":"Schuel","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.reprotox.2018.06.013","article-title":"Chronic cannabidiol exposure promotes functional impairment in sexual behavior and fertility of male mice","volume":"81","author":"Carvalho","year":"2018","journal-title":"Reprod. Toxicol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1080\/15592294.2018.1554521","article-title":"exposure and altered DNA methylation in rat and human sperm","volume":"13","author":"Murphy","year":"2018","journal-title":"Epigenetics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/j.watres.2008.11.056","article-title":"Monitoring of opiates, cannabinoids and their metabolites in wastewater, surface water and finished water in Catalonia, Spain","volume":"43","author":"Boleda","year":"2009","journal-title":"Water Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"115642","DOI":"10.1016\/j.envpol.2020.115642","article-title":"A critical review on the detection, occurrence, fate, toxicity, and removal of cannabinoids in the water system and the environment","volume":"268","author":"How","year":"2021","journal-title":"Environ. Pollut."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.envint.2009.10.004","article-title":"Drugs of abuse and their metabolites in the Ebro River basin: Occurrence in sewage and surface water, sewage treatment plants removal efficiency, and collective drug usage estimation","volume":"36","author":"Postigo","year":"2010","journal-title":"Environ. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.toxlet.2022.12.007","article-title":"Effects of prenatal exposure to THC on hippocampal neural development in offspring","volume":"374","author":"Peng","year":"2023","journal-title":"Toxicol. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.dcn.2015.07.004","article-title":"Impact of cannabis use on prefrontal and parietal cortex gyrification and surface area in adolescents and emerging adults","volume":"16","author":"Shollenbarger","year":"2015","journal-title":"Dev. Cogn. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e195","DOI":"10.1097\/ADM.0000000000000638","article-title":"Canadian cannabis consumption and patterns of congenital anomalies: An ecological geospatial analysis","volume":"14","author":"Reece","year":"2020","journal-title":"J. Addict. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/S0140-6736(68)90626-0","article-title":"Teratogenic activity of cannabis resin","volume":"292","author":"Persaud","year":"1968","journal-title":"Lancet"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s00213-010-1805-z","article-title":"Altered parahippocampal functioning in cannabis users is related to the frequency of use","volume":"209","author":"Becker","year":"2010","journal-title":"Psychopharmacology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.brainres.2013.11.002","article-title":"The behavioral effects of acute \u03949-tetrahydrocannabinol and heroin (diacetylmorphine) exposure in adult zebrafish","volume":"1543","author":"Stewart","year":"2014","journal-title":"Brain Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1093\/toxsci\/kfx232","article-title":"Developmental Effects of Cannabidiol and \u03949-Tetrahydrocannabinol in Zebrafish","volume":"162","author":"Carty","year":"2018","journal-title":"Toxicol. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3829","DOI":"10.1007\/s00213-014-3522-5","article-title":"Acute administration of THC impairs spatial but not associative memory function in zebrafish","volume":"231","author":"Ruhl","year":"2014","journal-title":"Psychopharmacology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"15693","DOI":"10.1038\/s41598-021-95016-4","article-title":"THC-induced behavioral stereotypy in zebrafish as a model of psychosis-like behavior","volume":"11","author":"Zarei","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/0041-008X(75)90209-4","article-title":"The toxicologic and teratologic effects of \u03949-tetrahydrocannabinol in the Zebrafish embryo","volume":"32","author":"Thomas","year":"1975","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1080\/15592294.2019.1695341","article-title":"The dynamics of DNA methylation during epigenetic reprogramming of primordial germ cells in medaka (Oryzias latipes)","volume":"15","author":"Wang","year":"2020","journal-title":"Epigenetics"},{"key":"ref_39","unstructured":"Couper, F.J., and Logan, B.K. (2014). Drugs and Human Performance Fact Sheets (DOT HS 809 725). Natl. Highw. Traffic Saf. Adm., 1\u2013100."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"W191","DOI":"10.1093\/nar\/gkz369","article-title":"g:Profiler: A web server for functional enrichment analysis and conversions of gene lists (2019 update)","volume":"47","author":"Raudvere","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"bav096","DOI":"10.1093\/database\/bav096","article-title":"Ensembl comparative genomics resources","volume":"2016","author":"Herrero","year":"2016","journal-title":"Database"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.aquatox.2019.04.005","article-title":"Bisphenol A and 17\u03b1-ethinylestradiol-induced transgenerational differences in expression of osmoregulatory genes in the gill of medaka (Oryzias latipes)","volume":"211","author":"Wang","year":"2019","journal-title":"Aquat. Toxicol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9303","DOI":"10.1038\/srep09303","article-title":"Transgenerational effects from early developmental exposures to bisphenol A or 17\u03b1-ethinylestradiol in medaka","volume":"5","author":"Bhandari","year":"2015","journal-title":"Oryzias latipes. Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"045001","DOI":"10.1289\/EHP2322","article-title":"Epigenetic applications in adverse outcome pathways and environmental risk evaluation","volume":"126","author":"Angrish","year":"2018","journal-title":"Environ. Health Perspect."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"103705","DOI":"10.1016\/j.mcn.2022.103705","article-title":"Differential expression of the neuronal CB1 cannabinoid receptor in the hippocampus of male Ts65Dn Down syndrome mouse model","volume":"119","author":"Drutel","year":"2022","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"C370","DOI":"10.1152\/ajpcell.00373.2021","article-title":"Chronic edible dosing of \u03949-tetrahydrocannabinol (THC) in non-human primates reduces systemic platelet activity and function","volume":"322","author":"Reitsma","year":"2022","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1089\/can.2017.0034","article-title":"Chronic adolescent \u03949-tetrahydrocannabinol treatment of male mice leads to long-term cognitive and behavioral dysfunction, which are prevented by concurrent cannabidiol treatment","volume":"2","author":"Murphy","year":"2017","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/sj.npp.1301475","article-title":"Adolescent Rats Find Repeated \u03949-THC Less Aversive Than Adult Rats but Display Greater Residual Cognitive Deficits and Changes in Hippocampal Protein Expression Following Exposure","volume":"33","author":"Quinn","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1006\/exnr.1996.0180","article-title":"Evidence for Physiological Down-regulation of Brain Oxidative Phosphorylation in Alzheimer\u2019s Disease","volume":"142","author":"Chandrasekaran","year":"1996","journal-title":"Exp. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/biof.1035","article-title":"COX-2 in the neurodegenerative process of Parkinson\u2019s disease","volume":"38","author":"Teismann","year":"2012","journal-title":"BioFactors"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1111\/j.1476-5381.2011.01418.x","article-title":"Role of LOX\/COX pathways in 3-nitropropionic acid-induced Huntington\u2019s Disease-like symptoms in rats: Protective effect of licofelone","volume":"164","author":"Kumar","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/0006-8993(95)01517-5","article-title":"Gene expression of ND4, a subunit of complex I of oxidative phosphorylation in mitochondria, is decreased in temporal cortex of brains of Alzheimer\u2019s disease patients","volume":"713","author":"Fukuyama","year":"1996","journal-title":"Brain Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Barbalho, P.G., Lopes-Cendes, I., and Maurer-Morelli, C.V. (2016). Indomethacin treatment prior to pentylenetetrazole-induced seizures downregulates the expression of il1b and cox2 and decreases seizure-like behavior in zebrafish larvae. BMC Neurosci., 17.","DOI":"10.1186\/s12868-016-0246-y"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"562","DOI":"10.2174\/156720508786898488","article-title":"Disease state, age, sex, and post-mortem time-dependent expression of proteins in AD vs. control frontal cortex brain samples","volume":"5","author":"Muller","year":"2008","journal-title":"Curr. Alzheimer Res."},{"key":"ref_55","first-page":"267","article-title":"The influence of delta9-tetrahydrocannabinol, cannabinol and cannabidiol on tissue oxygen consumption","volume":"12","author":"Chiu","year":"1975","journal-title":"Res. Commun. Chem. Pathol. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"L298","DOI":"10.1152\/ajplung.00157.2002","article-title":"Delta 9-tetrahydrocannabinol disrupts mitochondrial function and cell energetics","volume":"284","author":"Sarafian","year":"2003","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"323706","DOI":"10.1155\/2015\/323706","article-title":"Tetrahydrocannabinol induces brain mitochondrial respiratory chain dysfunction and increases oxidative stress: A potential mechanism involved in cannabis-related stroke","volume":"2015","author":"Wolff","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.pbb.2014.02.014","article-title":"Behavior, Chronic exposure to WIN55, 212-2 affects more potently spatial learning and memory in adolescents than in adult rats via a negative action on dorsal hippocampal neurogenesis","volume":"120","author":"Abboussi","year":"2014","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S0896-6273(00)80297-4","article-title":"A PDGF-regulated immediate early gene response initiates neuronal differentiation in ventricular zone progenitor cells","volume":"18","author":"Williams","year":"1997","journal-title":"Neuron"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1038\/nn954","article-title":"Suppressor of cytokine signaling 2 regulates neuronal differentiation by inhibiting growth hormone signaling","volume":"5","author":"Turnley","year":"2002","journal-title":"Nat. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/S0959-4388(00)00175-6","article-title":"Cell cycle and cell fate in the nervous system","volume":"11","author":"Ohnuma","year":"2001","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5698","DOI":"10.1128\/MCB.01833-07","article-title":"Cyclin-dependent kinase-associated proteins Cks1 and Cks2 are essential during early embryogenesis and for cell cycle progression in somatic cells","volume":"28","author":"Liberal","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"100202","DOI":"10.1074\/jbc.RA120.015877","article-title":"Elongin A associates with actively transcribed genes and modulates enhancer RNA levels with limited impact on transcription elongation rate in vivo","volume":"296","author":"Ardehali","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"112627","DOI":"10.1016\/j.bbr.2020.112627","article-title":"CBD modulates DNA methylation in the prefrontal cortex and hippocampus of mice exposed to forced swim","volume":"388","author":"Sales","year":"2020","journal-title":"Behav. Brain Res."},{"key":"ref_65","first-page":"6078","article-title":"Transcriptional repression of the D-type cyclin-dependent kinase inhibitor p16 by the retinoblastoma susceptibility gene product pRb","volume":"54","author":"Li","year":"1994","journal-title":"Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/0091-3057(84)90111-4","article-title":"Behavior, Early cannabinoid exposure influences neuroendocrine and reproductive functions in mice: II. Postnatal effects","volume":"20","author":"Dalterio","year":"1984","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5554","DOI":"10.1128\/MCB.22.15.5554-5562.2002","article-title":"Testis-specific cytochrome c-null mice produce functional sperm but undergo early testicular atrophy","volume":"22","author":"Narisawa","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.chemosphere.2011.12.047","article-title":"Gene expression profiles in the testis associated with testis-ova in adult Japanese medaka (Oryzias latipes) exposed to 17\u03b1-ethinylestradiol","volume":"87","author":"Hirakawa","year":"2012","journal-title":"Chemosphere"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s00204-009-0479-y","article-title":"Cypermethrin exposure during puberty disrupts testosterone synthesis via downregulating StAR in mouse testes","volume":"84","author":"Wang","year":"2010","journal-title":"Arch. Toxicol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4849","DOI":"10.1016\/j.jmb.2018.09.016","article-title":"Regulation of Mitochondrial Electron Transport Chain Assembly","volume":"430","author":"Cogliati","year":"2018","journal-title":"J. Mol. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1093\/molbev\/msh031","article-title":"Evolution of interacting proteins in the mitochondrial electron transport system in a marine copepod","volume":"21","author":"Willett","year":"2004","journal-title":"Mol. Biol. Evol."}],"container-title":["Journal of Xenobiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2039-4713\/13\/2\/18\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:44:54Z","timestamp":1760125494000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2039-4713\/13\/2\/18"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,30]]},"references-count":71,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,6]]}},"alternative-id":["jox13020018"],"URL":"https:\/\/doi.org\/10.3390\/jox13020018","relation":{},"ISSN":["2039-4713"],"issn-type":[{"value":"2039-4713","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,30]]}}}