SPERMATOGENIC CELLS ON DEFINED SUBSTRATES FOR TOXICOLOGY

用于毒理学的特定基质上的生精细胞

• 批准号: 3499895
• 负责人: FREDERICK CAHN
• 金额: $ 5万
• 依托单位: BIOMAT CORPORATION
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-15 至 1992-03-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3499895
• 关键词: Sertoli cells; alternatives to animals in research; animal tissue; biomaterial evaluation; cell age; cell cycle; cell differentiation; cell type; chemical synthesis; chemotherapy; cis platinum compound; collagen; copolymer; crosslink; deficient growth media; dosage; electron microscopy; extracellular matrix; fertility; fluorouracil; gene expression; laboratory rat; male; mixed tissue /cell culture; mucopolysaccharides; northern blottings; reproductive hormone; spermatogenesis; thiotepa; toxicant screening

The goal of our Phase I research program is to establish culture conditions that will maintain differentiated cell functions in rat Sertoli cell- spermatogenic cell co-cultures for extended times, using defined substrates, and serum-free medium, and functional assays. The cultures will be evaluated for suitability for toxicological testing and reproductive hormone assays using as model toxicants chemotherapeutic drugs with known testicular toxicity. The defined substrates will be based on collagen-glycosaminoglycan crosslinked copolymers. Both increased longevity and additional stages of differentiation are important objectives for toxicological assays because they allow for better standardization of cultures, longer contact times for agents to be tested, identification of particularly sensitive spermatogenic cell types and differentiation substages, and greater sensitivity and range in observing toxic endpoints. Our data may also be of clinical significance since short term assays of effects of chemotherapeutic drugs on spermatogenic cell differentiation may be useful in predicting the potential of chemical-induced sterility in cancer patients of reproductive age. The use of drugs with lower toxicity to testicular cells may then be considered in these patients. Knowledge gained from our work may also have value in the understanding and treatment of human infertility.

我们第一阶段研究计划的目标是建立培养条件， 维持大鼠睾丸支持细胞的分化功能 生精细胞共培养延长时间，使用定义的 底物和无血清培养基以及功能测定。 培养物 将评价毒理学试验的适用性， 使用模型毒物化学治疗药物的生殖激素测定 已知睾丸中毒 定义的基质将基于 胶原-糖胺聚糖交联共聚物。 双双增长 寿命和分化的额外阶段是重要的目标 用于毒理学测定，因为它们允许更好地标准化 培养物，待测制剂的较长接触时间， 特别敏感的生精细胞类型和分化 在观察毒性终点时，具有更高的灵敏度和更大的范围。 我们的数据也可能具有临床意义，因为短期测定 化疗药物对生精细胞分化的影响可能 可用于预测化学诱导不育的可能性， 育龄期癌症患者。 使用低毒性药物 睾丸细胞，然后可以考虑在这些患者。 知识 从我们的工作中获得的可能也有价值的理解和治疗 人类不育症。