A microphysiological engineered 3D system to the rescue of ovarian follicles

用于拯救卵泡的微生理工程 3D 系统

• 批准号: 10221014
• 负责人: Ariella Shikanov
• 金额: $ 36.52万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10221014
• 关键词: 3-Dimensional; Algorithms; Autocrine Communication; Automobile Driving; Biological Assay; Biology; Biomimetics; Cells; Complex; Cryopreservation; Data; Development; Diagnosis; Embryo; Endocrine; Engineering; Event; Fertility; Follistatin; Gene Expression; Gene Expression Profile; Genes; Genetic Transcription; Goals; Graafian Follicles; Growth; Growth Factor; Human; Hydrogels; In Vitro; Individual; Knowledge; Malignant Neoplasms; Measures; Methods; Molecular Profiling; Monitor; Mus; Oocytes; Organ Culture Techniques; Organoids; Ovarian; Ovarian Follicle; Ovarian tissue cryopreservation; Ovary; Paracrine Communication; Pathway interactions; Performance; Positioning Attribute; Primordial Follicle; Process; Proteins; Proteomics; Research; Role; Route; Sampling; Series; Signal Transduction; Standardization; Structure; System; Systems Biology; Technology; Testing; Time; Time Series Analysis; Tissues; Translating; Translations; Validation; Vascular Endothelial Growth Factors; Woman; chemotherapy; cohort; cytokine; design; extracellular; folliculogenesis; girls; granulosa cell; growth promoting activity; high reward; high risk; prepuberty; preservation; programs; receptor; success; theca cell; transcription factor; transcriptome sequencing; treatment strategy; young woman

Project Summary Ovarian follicles are the functional multicellular units of the ovary responsible for a woman’s fertility and ovarian endocrine function. Currently, young women and prepubertal girls diagnosed with cancer and facing ovo-toxic treatments have limited options to preserve their fertility, with cryopreservation of ovarian tissue prior to chemotherapy being the most promising route. Only primordial and early-stage primary follicles survive cryopreservation. To grow and mature, follicles have to be isolated and cultured in groups, because they die if cultured individually. Culture of isolated early follicles as groups has limited translational potential, because of different developmental stages and varying quality of follicles in the cohort, thus emphasizing the need to develop approaches to successfully culture early follicles individually. The low success rates of in vitro follicle development are attributed to the complex and poorly understood paracrine and autocrine signaling between the cells in a follicle, neighboring follicles and their microenvironment. Our overall research objectives are: (a) to identify key factors essential for activation and growth of early stage follicles in vitro, (b) to establish networks and functional relationships between secreted factors, downstream receptors and transcription factors, and (c) to create a standardized in vitro culture system that promotes growth and maturation of early follicles individually. The novelty and the significance of the proposed research are in the discovery of key factors that control and direct the earliest stages of ovarian follicle development. Application of a systems biology approach to study dynamic processes in complex multicellular organoid structures, such as follicles, has the potential to translate to human follicles and study the development and interplay in other tissue organoids and embryos.

项目概要 卵巢卵泡是卵巢的功能性多细胞单位，负责女性的生育能力和 目前，年轻女性和青春期前的女孩被诊断患有癌症并面临卵巢内分泌功能。 卵毒性治疗在保护其生育能力方面的选择有限，需要先冷冻卵巢组织 化疗是最有希望的途径，只有原始和早期的初级卵泡才能存活。 为了生长和成熟，卵泡必须被分离并成组培养，因为如果卵泡死亡，它们就会死亡。 单独培养的早期卵泡作为群体进行培养的转化潜力有限，因为 队列中不同的发育阶段和不同的卵泡质量，因此强调需要 开发成功单独培养早期卵泡的方法体外卵泡的成功率较低。 发育归因于复杂且知之甚少的旁分泌和自分泌信号传导 我们的总体研究目标是：（a）毛囊中的细胞、邻近毛囊及其微环境。 确定体外早期卵泡激活和生长所必需的关键因素，(b) 建立 分泌因子、下游受体和转录之间的网络和功能关系 因素，以及（c）创建一个标准化的体外培养系统，促进早期细胞的生长和成熟 所提出的研究的新颖性和意义在于关键的发现。 控制和指导卵巢卵泡发育最早阶段的因素系统的应用。 研究复杂多细胞类器官结构（例如卵泡）动态过程的生物学方法 有潜力转化为人类卵泡并研究其他组织的发育和相互作用 器官和胚胎。