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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 该项目是路线图联盟 (U54RR02437/T. Woodruff, PI) 的一部分，题为“肿瘤生育联盟：女性生育力保存”。其目标是通过防止卵巢暴露于治疗的配子毒性作用（通过切除和保存活检）并返回卵巢组织、配子或胚胎，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。 在猴子身上进行的研究：（目标 1）通过生物工程设计一种支架，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。 未成熟的卵泡将从卵巢中分离出来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。 卵泡在体外和皮质移植中产生的成熟卵母细胞将通过体外受精、胚胎移植到代孕母亲、怀孕和后代的健康来评估生殖潜力。 实验成功地在体外使小卵泡生长到窦期超过30天，促进类固醇生成（黄体酮、雌激素）和旁分泌（抗苗勒氏管激素、血管内皮生长因子）功能，并产生可在体外受精的减数分裂成熟卵子。