BIOENGINEERING PRIMATE FOLLICLES: FROM IMMATURE EGGS TO LIVE BIRTHS

灵长类卵泡生物工程：从未成熟卵子到活产

• 批准号: 8173220
• 负责人: RICHARD L STOUFFER
• 金额: $ 9.51万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173220
• 关键词: Abdomen; Alginates; Angiogenic Factor; Antral; Architecture; Autologous Transplantation; Biological Preservation; Biomedical Engineering; Biopsy; Cancer Survivor; Computer Retrieval of Information on Scientific Projects Database; Cortex of ovary; Development; Embryo; Embryo Transfer; Exposure to; Female; Fertility; Fertilization; Fertilization in Vitro; Forearm; Funding; Germ Cells; Goals; Graafian Follicles; Grant; Growth; Growth Factor; Health; Hormones; In Vitro; Institution; Live Birth; Macaca; Monitor; Monkeys; Mothers; Oocytes; Ovarian; Ovarian Tissue; Ovary; Pregnancy; Primates; Research; Research Personnel; Resources; Role; Site; Source; Staging; Transplantation; United States National Institutes of Health; Woman; egg; in vivo; nonhuman primate; offspring; oocyte maturation; prevent; reproductive; research study; scaffold

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project is part of a Roadmap Consortium (U54 RR02437, T. Woodruff, PI) entitled "The Oncofertility Consortium: Fertility Preservation for Women". This project's goal is to validate options in nonhuman primates for restoring fertility in female cancer survivors by preventing ovarian exposure to the gametotoxic effects of therapy (by removing and preserving biopsies) and returning ovarian tissue, gametes or embryos for fertility. Studies will be performed in monkeys to: (Aim 1) Bioengineer a scaffold that supports the three-dimensional architecture of the follicle and permits coordinated development of the follicle wall and oocyte in vitro; (Aim 2) Evaluate the role of hormones and growth factors in promoting follicle growth and oocyte quality during culture; (Aim 3) Optimize conditions for autotransplantation of ovarian cortex for coordinated follicle growth and oocyte maturation in vivo; and (Aim 4) Assess fertilization and embryonic potential of oocytes derived from in vitro matured follicles and transplanted ovarian cortical follicles in vivo. Immature follicles will be isolated from macaque ovaries and cultured in an alginate matrix. Ovarian cortex will be autotransplanted to accessible sites (abdomen and forearm), and the ability of pro-angiogenic factors to restore ovarian function will be monitored. Mature oocytes produced by follicles in vitro and cortical transplants in vivo will be evaluated for reproductive potential by in vitro fertilization, embryo transfer into surrogate macaque mothers, pregnancy and health of offspring. Initial experiments were successful in growing small follicles for over 30 days in vitro to the antral stage and promoting steroidogenic function.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 该项目是题为“肿瘤生育联盟：女性生育力保存”的路线图联盟（U54 RR02437，T. Woodruff，PI）的一部分。该项目的目标是通过防止卵巢暴露于治疗的配子毒性作用（通过切除和保存活组织检查）以及恢复卵巢组织、配子或胚胎以实现生育能力，在非人类灵长类动物中验证恢复女性癌症幸存者生育能力的选择。 将在猴子中进行研究，以：（目标 1）通过生物工程设计支架，支持卵泡的三维结构，并允许卵泡壁和卵母细胞在体外协调发育； （目标2）评估培养过程中激素和生长因子在促进卵泡生长和卵母细胞质量方面的作用； （目标3）优化卵巢皮质自体移植条件，以协调体内卵泡生长和卵母细胞成熟； （目标 4）评估来自体外成熟卵泡和体内移植卵巢皮质卵泡的卵母细胞的受精和胚胎潜力。 将从猕猴卵巢中分离出未成熟的卵泡并在藻酸盐基质中培养。 卵巢皮质将被自体移植到可触及的部位（腹部和前臂），并且将监测促血管生成因子恢复卵巢功能的能力。 体外卵泡和体内皮质移植产生的成熟卵母细胞将通过体外受精、胚胎移植到代孕猕猴体内、怀孕和后代的健康来评估生殖潜力。 初步实验成功地使小卵泡在体外生长了 30 多天，直至窦期并促进类固醇生成功能。