{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:50:27Z","timestamp":1791849027861,"version":"4.3.4"},"reference-count":53,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2024,11,1]],"date-time":"2024-11-01T00:00:00Z","timestamp":1730419200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.fr","clinicalkey.jp","clinicalkey.es","clinicalkey.com.au","clinicalkey.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology"],"published-print":{"date-parts":[[2024,11]]},"DOI":"10.1016\/j.tox.2024.153907","type":"journal-article","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T01:55:42Z","timestamp":1723082142000},"page":"153907","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"special_numbering":"C","title":["Exosomes-mediated retinoic acid disruption: A link between gut microbiota depletion and impaired spermatogenesis"],"prefix":"10.1016","volume":"508","author":[{"given":"Tong","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boqi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guitian","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caomeihui","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinxin","family":"Zong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunjin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.tox.2024.153907_bib1","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.4049\/jimmunol.179.3.1969","article-title":"Exosomes with immune modulatory features are present in human breast milk","volume":"179","author":"Admyre","year":"2007","journal-title":"J. Immunol."},{"key":"10.1016\/j.tox.2024.153907_bib2","doi-asserted-by":"crossref","first-page":"14976","DOI":"10.1073\/pnas.0807297105","article-title":"Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice","volume":"105","author":"Anderson","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.tox.2024.153907_bib3","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s12974-019-1494-4","article-title":"Antibiotics, gut microbiota, and Alzheimer's disease","volume":"16","author":"Angelucci","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"10.1016\/j.tox.2024.153907_bib4","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1093\/humrep\/deac015","article-title":"Sperm acquire epididymis-derived proteins through epididymosomes","volume":"37","author":"Barrachina","year":"2022","journal-title":"Hum. Reprod."},{"key":"10.1016\/j.tox.2024.153907_bib5","first-page":"143","article-title":"Oviductal extracellular vesicles (oviductosomes, OVS) are conserved in humans: murine OVS play a pivotal role in sperm capacitation and fertility","volume":"24","author":"Bathala","year":"2018","journal-title":"Mol. Hum. Reprod."},{"key":"10.1016\/j.tox.2024.153907_bib6","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1016\/j.chom.2022.06.011","article-title":"Gut commensals expand vitamin A metabolic capacity of the mammalian host","volume":"30","author":"Bonakdar","year":"2022","journal-title":"Cell Host Microbe"},{"key":"10.1016\/j.tox.2024.153907_bib7","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1016\/j.celrep.2018.06.111","article-title":"Retinoic acid antagonizes testis development in mice","volume":"24","author":"Bowles","year":"2018","journal-title":"Cell Rep."},{"key":"10.1016\/j.tox.2024.153907_bib8","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1126\/science.1125691","article-title":"Retinoid signaling determines germ cell fate in mice","volume":"312","author":"Bowles","year":"2006","journal-title":"Science"},{"key":"10.1016\/j.tox.2024.153907_bib9","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.chom.2022.07.010","article-title":"How the gut microbiota helps keep us vitaminized","volume":"30","author":"Brauer-Nikonow","year":"2022","journal-title":"Cell Host Microbe"},{"key":"10.1016\/j.tox.2024.153907_bib10","doi-asserted-by":"crossref","DOI":"10.3390\/biom10111510","article-title":"The biological function of extracellular vesicles during fertilization, early embryo-maternal crosstalk and their involvement in reproduction: review and overview","volume":"10","author":"Capra","year":"2020","journal-title":"Biomolecules"},{"key":"10.1016\/j.tox.2024.153907_bib11","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.apsb.2021.08.016","article-title":"Natural exosome-like nanovesicles from edible tea flowers suppress metastatic breast cancer via ROS generation and microbiota modulation","volume":"12","author":"Chen","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"10.1016\/j.tox.2024.153907_bib12","doi-asserted-by":"crossref","first-page":"33862","DOI":"10.1038\/srep33862","article-title":"Porcine milk-derived exosomes promote proliferation of intestinal epithelial cells","volume":"6","author":"Chen","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.tox.2024.153907_bib13","article-title":"Gut-derived exosomes mediate the microbiota dysbiosis-induced spermatogenesis impairment by targeting meioc in mice","volume":"11","author":"Chen","year":"2024","journal-title":"Adv. Sci. (Weinh.)"},{"key":"10.1016\/j.tox.2024.153907_bib14","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1053\/j.gastro.2022.10.018","article-title":"Gut microbiota modulation of efficacy and toxicity of cancer chemotherapy and immunotherapy","volume":"164","author":"Chrysostomou","year":"2023","journal-title":"Gastroenterology"},{"key":"10.1016\/j.tox.2024.153907_bib15","doi-asserted-by":"crossref","first-page":"12048","DOI":"10.1073\/pnas.1304718110","article-title":"Human placental trophoblasts confer viral resistance to recipient cells","volume":"110","author":"Delorme-Axford","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.tox.2024.153907_bib16","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1136\/gutjnl-2019-319127","article-title":"Impairment of spermatogenesis and sperm motility by the high-fat diet-induced dysbiosis of gut microbes","volume":"69","author":"Ding","year":"2020","journal-title":"Gut"},{"key":"10.1016\/j.tox.2024.153907_bib17","doi-asserted-by":"crossref","first-page":"E10132","DOI":"10.1073\/pnas.1710837114","article-title":"Periodic production of retinoic acid by meiotic and somatic cells coordinates four transitions in mouse spermatogenesis","volume":"114","author":"Endo","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.tox.2024.153907_bib18","doi-asserted-by":"crossref","first-page":"12745","DOI":"10.1002\/jcp.27894","article-title":"Detection of extracellular vesicles in the mouse vaginal fluid: their delivery of sperm proteins that stimulate capacitation and modulate fertility","volume":"234","author":"Fereshteh","year":"2019","journal-title":"J. Cell Physiol."},{"key":"10.1016\/j.tox.2024.153907_bib19","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1080\/10408363.2016.1190682","article-title":"Extracellular vesicles in blood, milk and body fluids of the female and male urogenital tract and with special regard to reproduction","volume":"53","author":"Foster","year":"2016","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"10.1016\/j.tox.2024.153907_bib20","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.it.2021.11.005","article-title":"Metabolites and secretory immunoglobulins: messengers and effectors of the host-microbiota intestinal equilibrium","volume":"43","author":"Goguyer-Deschaumes","year":"2022","journal-title":"Trends Immunol."},{"key":"10.1016\/j.tox.2024.153907_bib21","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/j.immuni.2018.11.018","article-title":"Commensals suppress intestinal epithelial cell retinoic acid synthesis to regulate interleukin-22 activity and prevent microbial dysbiosis","volume":"49","author":"Grizotte-Lake","year":"2018","journal-title":"Immunity"},{"key":"10.1016\/j.tox.2024.153907_bib22","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1172\/JCI41303","article-title":"The key role of vitamin A in spermatogenesis","volume":"120","author":"Hogarth","year":"2010","journal-title":"J. Clin. Invest"},{"key":"10.1016\/j.tox.2024.153907_bib23","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1016\/j.cmet.2021.08.006","article-title":"Exosomes as mediators of intercellular crosstalk in metabolism","volume":"33","author":"Isaac","year":"2021","journal-title":"Cell Metab."},{"key":"10.1016\/j.tox.2024.153907_bib24","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.devcel.2020.01.010","article-title":"MEIOSIN directs the switch from mitosis to meiosis in mammalian germ cells","volume":"52","author":"Ishiguro","year":"2020","journal-title":"Dev. Cell"},{"key":"10.1016\/j.tox.2024.153907_bib25","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21155377","article-title":"The Role of the Epididymis and the Contribution of Epididymosomes to Mammalian Reproduction","volume":"21","author":"James","year":"2020","journal-title":"Int J. Mol. Sci."},{"key":"10.1016\/j.tox.2024.153907_bib26","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1002\/hep.32608","article-title":"Probiotic-derived nanoparticles inhibit ALD through intestinal miR194 suppression and subsequent FXR activation","volume":"77","author":"Jiang","year":"2023","journal-title":"Hepatology"},{"key":"10.1016\/j.tox.2024.153907_bib27","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12958-018-0348-8","article-title":"Regulation by FSH of the dynamic expression of retinol-binding protein 4 in the mouse ovary","volume":"16","author":"Jiang","year":"2018","journal-title":"Reprod. Biol. Endocrinol."},{"key":"10.1016\/j.tox.2024.153907_bib28","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1186\/s40168-023-01659-y","article-title":"The gut metabolite 3-hydroxyphenylacetic acid rejuvenates spermatogenic dysfunction in aged mice through GPX4-mediated ferroptosis","volume":"11","author":"Jin","year":"2023","journal-title":"Microbiome"},{"key":"10.1016\/j.tox.2024.153907_bib29","doi-asserted-by":"crossref","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"Kalluri","year":"2020","journal-title":"Science"},{"key":"10.1016\/j.tox.2024.153907_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2021.103208","article-title":"Circulating exosomes and gut microbiome induced insulin resistance in mice exposed to intermittent hypoxia: effects of physical activity","volume":"64","author":"Khalyfa","year":"2021","journal-title":"EBioMedicine"},{"key":"10.1016\/j.tox.2024.153907_bib31","doi-asserted-by":"crossref","first-page":"1042923","DOI":"10.3389\/fmicb.2022.1042923","article-title":"Chronic alcohol-induced dysbiosis of the gut microbiota and gut metabolites impairs sperm quality in mice","volume":"13","author":"Li","year":"2022","journal-title":"Front. Microbiol."},{"key":"10.1016\/j.tox.2024.153907_bib32","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s40035-022-00323-z","article-title":"Gut microbiome, cognitive function and brain structure: a multi-omics integration analysis","volume":"11","author":"Liang","year":"2022","journal-title":"Transl. Neurodegener."},{"key":"10.1016\/j.tox.2024.153907_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.scitotenv.2021.150368","article-title":"Glyphosate-induced gut microbiota dysbiosis facilitates male reproductive toxicity in rats","volume":"805","author":"Liu","year":"2022","journal-title":"Sci. Total Environ."},{"key":"10.1016\/j.tox.2024.153907_bib34","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s12958-018-0371-9","article-title":"Follicle-stimulating hormone (FSH) promotes retinol uptake and metabolism in the mouse ovary","volume":"16","author":"Liu","year":"2018","journal-title":"Reprod. Biol. Endocrinol."},{"key":"10.1016\/j.tox.2024.153907_bib35","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1093\/humrep\/dead015","article-title":"The emerging role of extracellular vesicles in the testis","volume":"38","author":"Ma","year":"2023","journal-title":"Hum. Reprod."},{"key":"10.1016\/j.tox.2024.153907_bib36","first-page":"182","article-title":"Extracellular vesicles: roles in gamete maturation, fertilization and embryo implantation","volume":"22","author":"Machtinger","year":"2016","journal-title":"Hum. Reprod. Update"},{"key":"10.1016\/j.tox.2024.153907_bib37","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12943-019-0991-5","article-title":"Exosomes: composition, biogenesis, and mechanisms in cancer metastasis and drug resistance","volume":"18","author":"Mashouri","year":"2019","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.tox.2024.153907_bib38","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/j.devcel.2010.09.010","article-title":"The mammalian doublesex homolog DMRT1 is a transcriptional gatekeeper that controls the mitosis versus meiosis decision in male germ cells","volume":"19","author":"Matson","year":"2010","journal-title":"Dev. Cell"},{"key":"10.1016\/j.tox.2024.153907_bib39","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1210\/en.2018-00836","article-title":"Circulating exosomal miRNA profile during term and preterm birth pregnancies: a longitudinal study","volume":"160","author":"Menon","year":"2019","journal-title":"Endocrinology"},{"key":"10.1016\/j.tox.2024.153907_bib40","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1210\/en.2018-00820","article-title":"Quantitative proteomics by SWATH-MS of maternal plasma exosomes determine pathways associated with term and preterm birth","volume":"160","author":"Menon","year":"2019","journal-title":"Endocrinology"},{"key":"10.1016\/j.tox.2024.153907_bib41","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2021.119336","article-title":"Amniotic fluid-derived exosomes improved spermatogenesis in a rat model of azoospermia","volume":"274","author":"Mobarak","year":"2021","journal-title":"Life Sci."},{"key":"10.1016\/j.tox.2024.153907_bib42","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/S2468-1253(22)00241-2","article-title":"The intestinal barrier in disorders of the central nervous system","volume":"8","author":"Pellegrini","year":"2023","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"10.1016\/j.tox.2024.153907_bib43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bcmd.2005.03.005","article-title":"Role of exosomes in sperm maturation during the transit along the male reproductive tract","volume":"35","author":"Sullivan","year":"2005","journal-title":"Blood Cells Mol. Dis."},{"key":"10.1016\/j.tox.2024.153907_bib44","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s12915-022-01326-y","article-title":"Elevated testicular apoptosis is associated with elevated sphingosine driven by gut microbiota in prediabetic sheep","volume":"20","author":"Sun","year":"2022","journal-title":"BMC Biol."},{"key":"10.1016\/j.tox.2024.153907_bib45","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1039\/D1FO03145G","article-title":"Chestnut polysaccharides restore impaired spermatogenesis by adjusting gut microbiota and the intestinal structure","volume":"13","author":"Sun","year":"2022","journal-title":"Food Funct."},{"key":"10.1016\/j.tox.2024.153907_bib46","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41577-019-0198-4","article-title":"The intestinal microbiota fuelling metabolic inflammation","volume":"20","author":"Tilg","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.tox.2024.153907_bib47","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1016\/j.cmet.2022.08.004","article-title":"Extracellular vesicles mediate the communication of adipose tissue with brain and promote cognitive impairment associated with insulin resistance","volume":"34","author":"Wang","year":"2022","journal-title":"Cell Metab."},{"key":"10.1016\/j.tox.2024.153907_bib48","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13287-023-03263-1","article-title":"Perinatal tissue-derived exosomes ameliorate colitis in mice by regulating the Foxp3 + Treg cells and gut microbiota","volume":"14","author":"Yan","year":"2023","journal-title":"Stem Cell Res. Ther."},{"key":"10.1016\/j.tox.2024.153907_bib49","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1146\/annurev-animal-020518-115300","article-title":"Milk-derived exosomes and metabolic regulation","volume":"7","author":"Zempleni","year":"2019","journal-title":"Annu Rev. Anim. Biosci."},{"key":"10.1016\/j.tox.2024.153907_bib50","article-title":"Gut microbiota dysbiosis induced by decreasing endogenous melatonin mediates the pathogenesis of alzheimer's disease and obesity","volume":"13","author":"Zhang","year":"2022","journal-title":"Front Immunol."},{"key":"10.1016\/j.tox.2024.153907_bib51","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1136\/gutjnl-2020-320992","article-title":"Improvement in sperm quality and spermatogenesis following faecal microbiota transplantation from alginate oligosaccharide dosed mice","volume":"70","author":"Zhang","year":"2021","journal-title":"Gut"},{"key":"10.1016\/j.tox.2024.153907_bib52","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1136\/gutjnl-2020-323347","article-title":"Disrupted spermatogenesis in a metabolic syndrome model: the role of vitamin A metabolism in the gut-testis axis","volume":"71","author":"Zhang","year":"2022","journal-title":"Gut"},{"key":"10.1016\/j.tox.2024.153907_bib53","doi-asserted-by":"crossref","first-page":"3308","DOI":"10.7150\/thno.43189","article-title":"Alginate oligosaccharides improve germ cell development and testicular microenvironment to rescue busulfan disrupted spermatogenesis","volume":"10","author":"Zhao","year":"2020","journal-title":"Theranostics"}],"container-title":["Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X24001884?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X24001884?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T07:10:41Z","timestamp":1732605041000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0300483X24001884"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11]]},"references-count":53,"alternative-id":["S0300483X24001884"],"URL":"https:\/\/doi.org\/10.1016\/j.tox.2024.153907","relation":{},"ISSN":["0300-483X"],"issn-type":[{"value":"0300-483X","type":"print"}],"subject":[],"published":{"date-parts":[[2024,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Exosomes-mediated retinoic acid disruption: A link between gut microbiota depletion and impaired spermatogenesis","name":"articletitle","label":"Article Title"},{"value":"Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tox.2024.153907","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"153907"}}