AMH AS PREDICTOR OF FOLLICLE FUNCTION DURING ENCAPSULATED 3D CULTURE IN MACAQUES

AMH 作为猕猴封装 3D 培养期间卵泡功能的预测因子

• 批准号: 8357774
• 负责人: Mary B Zelinski
• 金额: $ 1.82万
• 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/8357774
• 关键词: 3-Dimensional; Adverse effects; Agonist; Antral; Biological Preservation; Cancer Patient; Cell Death; Cells; Cessation of life; Clinical; DNA Damage; Development; Embryonic Development; Encapsulated; Exposure to; Failure; Female; Fertility; Fertilization; Funding; Grant; Growth; Health; Infusion procedures; Life; Live Birth; Macaca; Malignant Neoplasms; Mus; National Center for Research Resources; Oocytes; Ovarian; Ovary; Pathway interactions; Pattern; Periodicity; Prevention; Primates; Principal Investigator; Production; Quality of life; Radiation; Radio; Research; Research Infrastructure; Resources; Source; Sphingosine; Steroids; Survival Rate; System; Toxic effect; Translating; United States National Institutes of Health; Vascular Endothelial Growth Factors; Woman; cancer therapy; cell type; chemotherapy; cohort; cost; girls; inorganic phosphate; intraovarian; irradiation; malignant breast neoplasm; mullerian-inhibiting hormone; nonhuman primate; novel strategies; offspring; oocyte maturation; preimplantation

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. Ovarian failure is a common side-effect of radiation or chemotherapy treatment in girls and young women. In view of increasing survival rates, especially in breast cancer patients, long-term consequences of cancer treatments with respect to fertility are important considerations for quality of life after cancer. Novel strategies for protecting the ovaries from adverse effects of cancer therapies are currently under development. For example, direct ovarian exposure to sphingosine-I-phosphate (SIP) prior to radio-or chemotherapy in mice maintains the health and function of follicles and their enclosed oocytes from damage such that fertilization and birth of live offspring are possible. These studies have been extended to nonhuman primates wherein intraovarian infusion of SIP or SIP agonist prior to X-irradiation protects a cohort of follicles that leads to normal ovarian/menstrual cyclicity, production of mature oocytes capable of preimplantation embryonic development and live offspring devoid of DNA damage. One mechanism whereby SIP agonists confer ovarian protection involves the prevention of oocyte death by interference in the cell death pathway induced by radiation. We are investigating whether other ovarian cell types, i.e. follicular cells surrounding the oocyte and/or the ovarian vasculature, are also spared from the toxic effects of radiation with SIP agonist treatment in macaques. Preantral follicles isolated from macaque ovaries and encapsulated for 3-dimensional culture secrete steroids and local nonsteroidal factors (anti-Mullerian hormone [AMH], vascular endothelial growth factor [VEGF]) depending on duration and growth rate in culture. Early antral development is associated with increased steroid and VEGF, but decreased AMH, secretion. AMH levels did not correlate with oocyte maturation or health. Thus, the pattern of follicle growth, but not oocyte maturation, can be determined from AMH levels during the first 2 weeks of culture. Efforts continue to optimize a follicle culture system in macaques that can be translated to clinical use for fertility preservation in female cancer patients.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 卵巢衰竭是女孩和年轻女性的辐射或化学疗法治疗的常见副作用。鉴于生存率提高，尤其是在乳腺癌患者中，癌症治疗对生育的长期后果是癌后生活质量的重要考虑因素。 目前正在开发保护卵巢免受癌症疗法不良影响的新型策略。 例如，在小鼠进行无线电或化学疗法之前，直接卵巢暴露于鞘氨醇 - 磷酸盐（SIP）中，可以维持卵泡的健康和功能及其封闭的卵母细胞，从而受到损害，以使生物后代的受精和出生是可能的。 这些研究已扩展到非人类灵长类动物，其中X射线之前对sip或sip激动剂的输注保护了一系列卵泡，从而导致正常的卵巢/月经周期性，产生能够产生能够实现胚胎胚胎胚胎发育的成熟卵母细胞，并实现胚胎胚胎的生命和实时攻击性脱落DNA损害。 SIP激动剂赋予卵巢保护的一种机制是通过干扰辐射引起的细胞死亡途径来预防卵母细胞死亡。 我们正在研究其他卵巢细胞类型，即卵母细胞和/或卵巢脉管系统周围的卵泡细胞是否也免于猕猴中的sip agonist治疗对辐射的毒性作用。从猕猴卵巢中分离出来的尿下卵泡，并囊括了三维培养物，分泌类固醇和局部非甾体类因子（抗毛酸激素[AMH] [AMH]，血管内皮生长因子[VEGF]），具体取决于培养的持续时间和生长速度。 早期的肛门发育与类固醇和VEGF的增加有关，但分泌AMH。 AMH水平与卵母细胞的成熟或健康无关。 因此，在培养的前2周，可以从AMH水平确定卵泡生长的模式，而不是卵母细胞的成熟。 努力继续优化猕猴中的卵泡培养系统，这些系统可以转化为女性癌症患者生育能力的临床用途。