Innovative three-dimensional testicular Co-culture (Mini-Testis) model for reproductive toxicity testing: a pathway based High throughput (HT) and High Content Analysis (HCA)

用于生殖毒性测试的创新三维睾丸共培养（迷你睾丸）模型：基于途径的高通量（HT）和高内涵分析（HCA）

• 批准号: 9198371
• 负责人: Lei Yin
• 金额: $ 20.21万
• 依托单位: REPROTOX BIOTECH, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9198371
• 关键词: Animal Testing; Animals; Biological Assay; Biological Markers; Cadmium; Cell Culture Techniques; Cell Cycle Regulation; Cell Line; Cell Survival; Cells; Cellular Morphology; Chemicals; Chronic; Coculture Techniques; Complex; Computer Simulation; DNA Damage; Data; Databases; Development; Dose; Esters; Evaluation; Generations; Gold; In Vitro; Life; Modeling; Molecular; National Research Council; Outcome; Oxidative Stress; Pathway interactions; Procedures; Protocols documentation; Public Health; Rattus; Reporting; Research; Risk Assessment; Spermatogenesis; Spermatogonia; Staging; Steroid biosynthesis; System; Testicular Tissue; Testing; Testis; Time; Toxic effect; Toxicity Tests; base; body system; cost efficient; cytotoxicity; design; developmental toxicity; high throughput screening; in vitro Model; in vivo; innovation; leydig interstitial cell; phthalates; predictive modeling; reproductive; reproductive toxicity; response; screening; tool; toxicant

Summary The need to identify chemicals for their potential to cause reproductive and developmental (R/D) toxicity (R/D) is a significant public health challenge for toxicologists. In vivo testing for reproductive and developmental toxicity assessment uses a large number of animals, yet these studies are criticized for their inefficiency. The National Research Council (NRC)’s report “Toxicity Testing in the 21st Century” envisioned that in vivo animal testing will eventually be replaced by a combination of in silico and in vitro approaches. Therefore, the need to identify in vitro systems for reproductive and developmental toxicity testing has grown. ReproTOX has established an animal-free testicular cell co-culture system (Mini-Testis) from testicular cell lines. Both morphology and cellular biomarkers confirmed that this animal-free 3D-co-culture model support in vitro spermatogenesis. Our 32-compound preliminary study revealed a stronger correlation of IC50 from the Mini-Testis model with in vivo reproductive toxicity as compared to any single testicular cell culture model. These initial results suggest that our Mini-Testis model might be a valuable screening tool for reproductive toxicants and prioritizing chemicals for further testing. The specific aims of this proposal, therefore, are to (1) establish a toxicity-based high throughput Mini-Testis model for R/D toxicity evaluation and (2) develop an integrated pathway-based high content (HCA) and high throughput (HT) screening assay in the Mini-Testis model for R/D toxicity evaluation. The project outcome will be a cost-efficient, pathway-based in vitro Mini- Testis model for potential R/D toxicity screening of chemicals.

总结

项目成果

Arsenic-induced apoptosis in the p53-proficient and p53-deficient cells through differential modulation of NFkB pathway.

• DOI: 10.1016/j.fct.2018.06.053
• 发表时间: 2018-08
• 期刊: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
• 作者: Yin L;Yu X
• 通讯作者: Yu X

Diazinon exposure activated transcriptional factors CCAAT-enhancer-binding proteins α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ) and induced adipogenesis in 3T3-L1 preadipocytes.

• DOI: 10.1016/j.pestbp.2018.07.003
• 发表时间: 2018-09
• 期刊: Pesticide biochemistry and physiology
• 影响因子: 4.7
• 作者: Smith A;Yu X;Yin L
• 通讯作者: Yin L