{"title":"Establishment of tumor microenvironment following bisphenol A exposure in the testis","authors":"","doi":"10.1016/j.ecoenv.2024.117071","DOIUrl":null,"url":null,"abstract":"<div><div>Although detrimental roles of bisphenol A (BPA) in xenoestrogen target organs, testis and epididymis, and male fertility are well-documented, disruption of the immune privilege system in the male reproductive tract following BPA exposure remains poorly understood. Therefore, this study aimed to explore the precise mechanisms of BPA in interfering immune privilege in the testis on RNA sequencing results. CD-1 male mice were daily treated no-observed-adverse-effect (NOAEL, 5 mg BPA/kg BW) and lowest-observed-adverse-effects (LOAEL, 50 mg BPA/kg BW) of BPA by oral gavage for 6 weeks. Following the LOAEL exposure, the expression of immune response-associated transcripts was upregulated in the testis. Moreover, BPA switch the testicular microenvironment to tumor friendly through the recruitment of tumor associated macrophages (TAMs), which can produce both anti- and pro-inflammatory cytokines, such as TNF-α, TLR2, IL-10, and CXCL9. Number of testicular blood vessels were approximately 2-times increased by upregulation of matrix metallopeptidase 2 in TAMs and upregulation of AR expression in the nucleus of Leydig cells. Moreover, we found that the tumor-supportive environment can also be generated even though NOAEL BPA concentration due to the individual’s variability in cancer susceptibility.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":null,"pages":null},"PeriodicalIF":6.2000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0147651324011473/pdfft?md5=ff1d109885af135076cecfdccf14677a&pid=1-s2.0-S0147651324011473-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ecotoxicology and Environmental Safety","FirstCategoryId":"93","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0147651324011473","RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Although detrimental roles of bisphenol A (BPA) in xenoestrogen target organs, testis and epididymis, and male fertility are well-documented, disruption of the immune privilege system in the male reproductive tract following BPA exposure remains poorly understood. Therefore, this study aimed to explore the precise mechanisms of BPA in interfering immune privilege in the testis on RNA sequencing results. CD-1 male mice were daily treated no-observed-adverse-effect (NOAEL, 5 mg BPA/kg BW) and lowest-observed-adverse-effects (LOAEL, 50 mg BPA/kg BW) of BPA by oral gavage for 6 weeks. Following the LOAEL exposure, the expression of immune response-associated transcripts was upregulated in the testis. Moreover, BPA switch the testicular microenvironment to tumor friendly through the recruitment of tumor associated macrophages (TAMs), which can produce both anti- and pro-inflammatory cytokines, such as TNF-α, TLR2, IL-10, and CXCL9. Number of testicular blood vessels were approximately 2-times increased by upregulation of matrix metallopeptidase 2 in TAMs and upregulation of AR expression in the nucleus of Leydig cells. Moreover, we found that the tumor-supportive environment can also be generated even though NOAEL BPA concentration due to the individual’s variability in cancer susceptibility.
期刊介绍:
Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.