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: 8357761
• 负责人: RICHARD L STOUFFER
• 金额: $ 7.28万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357761
• 关键词: Abdomen; Alginates; Angiogenic Factor; Antral; Architecture; Autologous Transplantation; Biological Preservation; Biomedical Engineering; Biopsy; Cancer Survivor; Cortex of ovary; Development; Embryo; Embryo Transfer; Estrogens; Exposure to; Female; Fertility; Fertilization; Fertilization in Vitro; Forearm; Funding; Germ Cells; Goals; Graafian Follicles; Grant; Growth; Growth Factor; Health; Hormones; In Vitro; Live Birth; Monitor; Monkeys; National Center for Research Resources; Oocytes; Ovarian; Ovarian Tissue; Ovary; Pregnancy; Primates; Principal Investigator; Progesterone; Research; Research Infrastructure; Resources; Role; Site; Source; Staging; Surrogate Mothers; Transplantation; United States National Institutes of Health; Vascular Endothelial Growth Factors; Woman; cost; egg; in vivo; mullerian-inhibiting hormone; nonhuman primate; offspring; oocyte maturation; paracrine; prevent; reproductive; research study; scaffold; zygote

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project is part of a Roadmap Consortium (U54RR02437/ T. Woodruff, PI) entitled "The Oncofertility Consortium: Fertility Preservation for Women". It'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. Studies in monkeys: (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 role of hormones and growth factors in promoting follicle growth and oocyte quality; (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 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 in cortical transplants will be evaluated for reproductive potential by in vitro fertilization, embryo transfer into surrogate mothers, pregnancy and health of offspring. Experiments were successful in growing small follicles for over 30 days in vitro to the antral stage, in promoting steroidogenic (progesterone, estrogen) and paracrine (anti-mullerian hormone, vascular endothelial growth factor) function, and producing meiotically mature eggs that fertilize in vitro.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 该项目是路线图联盟（U 54 RR 02437/ T）的一部分。Woodruff，PI），题为“The Oncofertility Consortium：Fertility Preservation for Women”。它的目标是通过防止卵巢暴露于治疗的配子毒性作用（通过去除和保存活检）并返回卵巢组织，配子或胚胎来验证非人类灵长类动物恢复女性癌症幸存者生育能力的选择。 猴研究：（目的1）构建一种支持卵泡三维结构的生物支架，使卵泡壁和卵母细胞在体外协调发育;（目的2）评价激素和生长因子在促进卵泡生长和卵母细胞质量中的作用;（目的3）优化自体卵巢皮质移植的条件，使卵泡生长和卵母细胞在体内协调成熟;目的4评价体外成熟卵泡卵母细胞和皮质卵泡卵母细胞移植后的受精和胚胎发育潜能。 将从卵巢中分离未成熟卵泡，并在藻酸盐基质中培养。 将卵巢皮质自体移植到可触及部位（腹部和前臂），并监测促血管生成因子恢复卵巢功能的能力。 将通过体外受精、胚胎移植到代孕母亲体内、妊娠和后代健康来评价体外和皮质移植中卵泡产生的成熟卵母细胞的生殖潜力。 实验成功地使小卵泡在体外生长超过30天至窦期，促进类固醇生成（孕酮、雌激素）和旁分泌（抗苗勒管激素、血管内皮生长因子）功能，并产生体外受精的减数分裂成熟卵子。