{"title":"Exosomes-mediated retinoic acid disruption: A link between gut microbiota depletion and impaired spermatogenesis","authors":"","doi":"10.1016/j.tox.2024.153907","DOIUrl":null,"url":null,"abstract":"<div><p>Gut microbiota symbiosis faces enormous challenge with increasing exposure to drugs such as environmental poisons and antibiotics. The gut microbiota is an important component of the host microbiota and has been proven to be involved in regulating spermatogenesis, but the molecular mechanism is still unclear. A male mouse model with gut microbiota depletion/dysbiosis was constructed by adding combined antibiotics to free drinking water, and reproductive parameters such as epididymal sperm count, testicular weight and paraffin sections were measured. Testicular transcriptomic and serum metabolomic analyses were performed to reveal the molecular mechanism of reproductive dysfunction induced by gut microbiota dysbiosis in male mice.This study confirms that antibiotic induced depletion of gut microbiota reduces sperm count in the epididymis and reduces germ cells in the seminiferous tubules in male mice. Further study showed that exosomes isolated from microbiota-depleted mice led to abnormally high levels of retinoic acid and decrease in the number of germ cells in the seminiferous tubules and sperm in the epididymis. Finally, abnormally high levels of retinoic acid was confirmed to disrupted meiotic processes, resulting in spermatogenesis disorders. This study proposed the concept of the gut microbiota-exosome-retinoic acid-testicular axis and demonstrated that depletion of the gut microbiota caused changes in the function of exosomes, which led to abnormal retinoic acid metabolism in the testis, thereby impairing meiosis and spermatogenesis processes.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0300483X24001884","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Gut microbiota symbiosis faces enormous challenge with increasing exposure to drugs such as environmental poisons and antibiotics. The gut microbiota is an important component of the host microbiota and has been proven to be involved in regulating spermatogenesis, but the molecular mechanism is still unclear. A male mouse model with gut microbiota depletion/dysbiosis was constructed by adding combined antibiotics to free drinking water, and reproductive parameters such as epididymal sperm count, testicular weight and paraffin sections were measured. Testicular transcriptomic and serum metabolomic analyses were performed to reveal the molecular mechanism of reproductive dysfunction induced by gut microbiota dysbiosis in male mice.This study confirms that antibiotic induced depletion of gut microbiota reduces sperm count in the epididymis and reduces germ cells in the seminiferous tubules in male mice. Further study showed that exosomes isolated from microbiota-depleted mice led to abnormally high levels of retinoic acid and decrease in the number of germ cells in the seminiferous tubules and sperm in the epididymis. Finally, abnormally high levels of retinoic acid was confirmed to disrupted meiotic processes, resulting in spermatogenesis disorders. This study proposed the concept of the gut microbiota-exosome-retinoic acid-testicular axis and demonstrated that depletion of the gut microbiota caused changes in the function of exosomes, which led to abnormal retinoic acid metabolism in the testis, thereby impairing meiosis and spermatogenesis processes.
期刊介绍:
Toxicology is an international, peer-reviewed journal that publishes only the highest quality original scientific research and critical reviews describing hypothesis-based investigations into mechanisms of toxicity associated with exposures to xenobiotic chemicals, particularly as it relates to human health. In this respect "mechanisms" is defined on both the macro (e.g. physiological, biological, kinetic, species, sex, etc.) and molecular (genomic, transcriptomic, metabolic, etc.) scale. Emphasis is placed on findings that identify novel hazards and that can be extrapolated to exposures and mechanisms that are relevant to estimating human risk. Toxicology also publishes brief communications, personal commentaries and opinion articles, as well as concise expert reviews on contemporary topics. All research and review articles published in Toxicology are subject to rigorous peer review. Authors are asked to contact the Editor-in-Chief prior to submitting review articles or commentaries for consideration for publication in Toxicology.