Se-Ra Park, Myung Geun Kook, Soo-Rim Kim, Choon-Mi Lee, Jin Woo Lee, Jung-Kyu Park, Chan Hum Park, Byung-Chul Oh, YunJae Jung, In-Sun Hong
{"title":"Development of a novel testis-on-a-chip that demonstrates reciprocal crosstalk between Sertoli and Leydig cells in testicular tissue","authors":"Se-Ra Park, Myung Geun Kook, Soo-Rim Kim, Choon-Mi Lee, Jin Woo Lee, Jung-Kyu Park, Chan Hum Park, Byung-Chul Oh, YunJae Jung, In-Sun Hong","doi":"10.1038/s12276-024-01258-3","DOIUrl":null,"url":null,"abstract":"The reciprocal crosstalk between testicular Sertoli and Leydig cells plays a vital role in supporting germ cell development and maintaining testicular characteristics and spermatogenesis. Conventional 2D and the recent 3D assay systems fail to accurately replicate the dynamic interactions between these essential endocrine cells. Furthermore, most in vitro testicular tissue models lack the ability to capture the complex multicellular nature of the testis. To address these limitations, we developed a 3D multicellular testis-on-a-chip platform that effectively demonstrates the reciprocal crosstalk between Sertoli cells and the adjacent Leydig cells while incorporating various human testicular tissue constituent cells and various natural polymers infused with blood coagulation factors. Additionally, we identified SERPINB2 as a biomarker of male reproductive toxicity that is activated in both Sertoli and Leydig cells upon exposure to various toxicants. Leveraging this finding, we designed a fluorescent reporter-conjugated toxic biomarker detection system that enables both an intuitive and quantitative assessment of material toxicity by measuring the converted fluorescence intensity. By integrating this fluorescent reporter system into the Sertoli and Leydig cells within our 3D multicellular chip platform, we successfully developed a testis-on-chip model that can be utilized to evaluate the male reproductive toxicity of potential drug candidates. This innovative approach holds promise for advancing toxicity screening and reproductive research. Spermatogenesis, or sperm creation, happens in the testis and involves various cells, including Sertoli and Leydig cells. However, traditional single-cell-based 2D assay models (tests that measure the presence of a substance) don’t accurately show the complex interactions between these cells. To solve this, scientists created a ‘human testis-on-a-chip’ platform that imitates the complex cell interactions and hormone communication of seminiferous tubules (small tubes) in the testis. The chip was made using polydimethylsiloxane (a type of silicone) and included multiple testicular tissue cells. The scientists found that the chip could keep the cells alive and active for up to 28 days. Also, the chip was able to produce hormones and respond to hormonal stimulation. This study provides a useful tool for studying male reproductive biology and testing potential drugs. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.","PeriodicalId":50466,"journal":{"name":"Experimental and Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":9.5000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297247/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental and Molecular Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s12276-024-01258-3","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The reciprocal crosstalk between testicular Sertoli and Leydig cells plays a vital role in supporting germ cell development and maintaining testicular characteristics and spermatogenesis. Conventional 2D and the recent 3D assay systems fail to accurately replicate the dynamic interactions between these essential endocrine cells. Furthermore, most in vitro testicular tissue models lack the ability to capture the complex multicellular nature of the testis. To address these limitations, we developed a 3D multicellular testis-on-a-chip platform that effectively demonstrates the reciprocal crosstalk between Sertoli cells and the adjacent Leydig cells while incorporating various human testicular tissue constituent cells and various natural polymers infused with blood coagulation factors. Additionally, we identified SERPINB2 as a biomarker of male reproductive toxicity that is activated in both Sertoli and Leydig cells upon exposure to various toxicants. Leveraging this finding, we designed a fluorescent reporter-conjugated toxic biomarker detection system that enables both an intuitive and quantitative assessment of material toxicity by measuring the converted fluorescence intensity. By integrating this fluorescent reporter system into the Sertoli and Leydig cells within our 3D multicellular chip platform, we successfully developed a testis-on-chip model that can be utilized to evaluate the male reproductive toxicity of potential drug candidates. This innovative approach holds promise for advancing toxicity screening and reproductive research. Spermatogenesis, or sperm creation, happens in the testis and involves various cells, including Sertoli and Leydig cells. However, traditional single-cell-based 2D assay models (tests that measure the presence of a substance) don’t accurately show the complex interactions between these cells. To solve this, scientists created a ‘human testis-on-a-chip’ platform that imitates the complex cell interactions and hormone communication of seminiferous tubules (small tubes) in the testis. The chip was made using polydimethylsiloxane (a type of silicone) and included multiple testicular tissue cells. The scientists found that the chip could keep the cells alive and active for up to 28 days. Also, the chip was able to produce hormones and respond to hormonal stimulation. This study provides a useful tool for studying male reproductive biology and testing potential drugs. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
期刊介绍:
Experimental & Molecular Medicine (EMM) stands as Korea's pioneering biochemistry journal, established in 1964 and rejuvenated in 1996 as an Open Access, fully peer-reviewed international journal. Dedicated to advancing translational research and showcasing recent breakthroughs in the biomedical realm, EMM invites submissions encompassing genetic, molecular, and cellular studies of human physiology and diseases. Emphasizing the correlation between experimental and translational research and enhanced clinical benefits, the journal actively encourages contributions employing specific molecular tools. Welcoming studies that bridge basic discoveries with clinical relevance, alongside articles demonstrating clear in vivo significance and novelty, Experimental & Molecular Medicine proudly serves as an open-access, online-only repository of cutting-edge medical research.