한빛사논문
Se-Ra Park1,2,6, Myung Geun Kook1,2,6, Soo-Rim Kim1,2,6, Choon-Mi Lee1,2, Jin Woo Lee1,2, Jung-Kyu Park1,2, Chan Hum Park3, Byung-Chul Oh4, YunJae Jung5 and In-Sun Hong1,2
1Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21999, Republic of Korea.
2Department of Molecular Medicine, School of Medicine, Gachon University, Incheon 406-840, Republic of Korea.
3Department of Otolaryngology-Head and Neck Surgery, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, Republic of Korea.
4Department of Physiology, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon 21999, Republic of Korea.
5Department of Microbiology, College of Medicine, Gachon University, Incheon 21999, Korea.
6These authors contributed equally: Se-Ra Park, Myung Geun Kook, Soo-Rim Kim.
Corresponding author
Correspondence to In-Sun Hong.
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.
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