Testing The Health And Therapeutic Potential Of In Vitro Derived Oocytes For The Restoration Of Female Fertility And The Treatment of Infertility

测试体外卵母细胞的健康和治疗潜力,以恢复女性生育能力和治疗不孕症

基本信息

  • 批准号:
    MR/T025654/1
  • 负责人:
  • 金额:
    $ 166.78万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Research Grant
  • 财政年份:
    2020
  • 资助国家:
    英国
  • 起止时间:
    2020 至 无数据
  • 项目状态:
    未结题

项目摘要

The freezing and banking of very early-staged eggs within ovarian tissue has been successfully used to preserve the fertility of girls and young women who are likely to lose their ovarian function as a result of the destructive effects of cancer treatments. Small pieces of the ovary can be surgically recovered from patients and stored at liquid nitrogen temperatures for as long as required. When the patient wishes to start her family, her stored ovarian tissue is transplanted back into her body with aim of producing fertile oocytes and a pregnancy either naturally or with the help of assisted reproduction technologies such as in vitro fertilisation (IVF). Over 150 babies have now been born worldwide using this technology. However, the transplantation method for fertility restoration is not suitable for all cancer patients. For girls and women with blood diseases such as leukaemia, and/or cancers such as breast cancer there is a risk that the cancer will be restarted from the transplanted tissues. For these patients a safer option is to grow the early staged eggs from the frozen-thawed ovarian tissue to maturity in the laboratory- a technology called the in vitro growth and maturation (IVGM) of eggs. The laboratory grown eggs can then be fertilised using IVF so that healthy embryo(s) can be transferred to the patient to produce the desired pregnancy. These technologies can also be used treat healthy but infertile women who are undergoing assisted conception using donor eggs. The development of methods to grow eggs from their earliest stages in the laboratory is very challenging. Never-the-less advances are being made towards this goal. It is now possible to produce full sized, mature eggs in the laboratory in both humans and ruminant species such as cows and sheep. Two different culture approaches are showing significant promise these are: (i) a fast growth system over 21 days (FasGro); and (ii) a slow growth system over 40-60 days (SloGro). The FasGro and SloGro systems have been developed in parallel for both human and ruminant eggs. However, it is not yet clear which of these methods is best at producing healthy eggs that can be fertilised to produce embryos for future transfer to produce a pregnancy and baby. Before new technologies such as IVGM can be used to restore the fertility of cancer survivors or to treat infertile women it is essential that they are rigorously tested in a suitable animal model to prove they are both safe and effective. This project aims to test the potential of IVGM eggs to used as a treatment to restore fertility in women. Sheep ovary tissues will be used as a mimic for human ovaries. Specifically, the project will grow eggs in the laboratory from frozen-thawed sheep ovary tissues using the FasGro and SloGro methods. The project will test the health of the laboratory-grown eggs and their ability to be fertilised using IVF and to produce embryos that will implant and produce a pregnancy and live offspring. The nutritional and genetic fingerprints of laboratory-derived eggs and embryos will be combined with microscope imaging and used as health screens to confirm whether the IVGM eggs are normal when compared to similar cells grown naturally in the body. An embryo transfer trial will be conducted in sheep to establish which IVGM egg production method is most effective at delivering healthy lambs. Key measurements of health and development will be made in follow-up studies of the newborn offspring from laboratory-grown eggs. Monitoring will continue as the animals grow to adulthood and will be compared to naturally conceived animals. This research is vital to enable selection of the best IVGM method and to ensure that the technology is both efficient and safe before it is used to treat patients.
冷冻和储存卵巢组织内的早期卵子已成功地用于保护由于癌症治疗的破坏性影响而可能失去卵巢功能的女孩和年轻妇女的生育能力。卵巢的小块可以通过手术从患者身上回收,并在液氮温度下储存所需的时间。当患者希望组建家庭时,她储存的卵巢组织将被移植回她的体内,目的是自然或在体外受精(IVF)等辅助生殖技术的帮助下产生可受精的卵母细胞并怀孕。目前,全世界已有150多名婴儿使用这项技术出生。然而,用于恢复生育能力的移植方法并不适合所有癌症患者。对于患有白血病等血液病和/或乳腺癌等癌症的女孩和妇女来说,移植的组织有重新引发癌症的风险。对于这些患者来说,一个更安全的选择是在实验室中将冷冻解冻的卵巢组织中的早期卵子培养成熟-这种技术称为卵子的体外生长和成熟(IVGM)。然后可以使用IVF使实验室生长的卵子受精,以便将健康的胚胎转移到患者体内以产生所需的妊娠。这些技术也可以用于治疗健康但不孕的妇女,她们正在接受使用捐赠卵子的辅助受孕。在实验室中从最早阶段开始培养卵子的方法的开发是非常具有挑战性的。在实现这一目标方面,正在取得越来越大的进展。现在可以在实验室中在人类和反刍动物物种(如牛和羊)中产生完整大小的成熟卵子。两种不同的培养方法显示出显著的前景,它们是:(i)超过21天的快速生长系统(FasGro);和(ii)超过40-60天的缓慢生长系统(SloGro)。FasGro和SloGro系统已被平行开发用于人类和反刍动物卵。然而,目前还不清楚这些方法中哪种最适合生产健康的卵子,这些卵子可以受精以产生胚胎,供将来移植以产生怀孕和婴儿。在IVGM等新技术用于恢复癌症幸存者的生育能力或治疗不孕妇女之前,必须在合适的动物模型中进行严格的测试,以证明它们既安全又有效。 该项目旨在测试IVGM卵子作为恢复女性生育能力的治疗方法的潜力。绵羊卵巢组织将用作人类卵巢的模拟物。具体来说,该项目将在实验室中使用FasGro和SloGro方法从冷冻解冻的绵羊卵巢组织中培养卵子。该项目将测试实验室培养的卵子的健康状况及其使用IVF受精的能力,并产生植入并产生怀孕和活后代的胚胎。实验室来源的卵子和胚胎的营养和遗传指纹将与显微镜成像相结合,并用作健康筛查,以确认IVGM卵子与体内自然生长的类似细胞相比是否正常。将在绵羊中进行胚胎移植试验,以确定哪种IVGM卵子生产方法在生产健康羔羊方面最有效。对健康和发育的关键测量将在对实验室培育的卵子的新生后代的后续研究中进行。随着动物长大成人,监测将继续进行,并将与自然受孕的动物进行比较。这项研究对于选择最佳IVGM方法至关重要,并确保该技术在用于治疗患者之前既有效又安全。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Therapeutic Potential of In Vitro-Derived Oocytes for the Restoration and Treatment of Female Fertility.
体外卵母细胞恢复和治疗女性生育能力的治疗潜力。
Making a good egg: human oocyte health, aging, and in vitro development.
  • DOI:
    10.1152/physrev.00032.2022
  • 发表时间:
    2023-10-01
  • 期刊:
  • 影响因子:
    33.6
  • 作者:
    Telfer, Evelyn E.;Grosbois, Johanne;Odey, Yvonne L.;Rosario, Roseanne;Anderson, Richard A.
  • 通讯作者:
    Anderson, Richard A.
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Helen Picton其他文献

Icestart™ Enhances Cryopreservation Of Primary Mammalian Cells In Multiwell Plates
  • DOI:
    10.1016/j.cryobiol.2019.10.090
  • 发表时间:
    2019-12-01
  • 期刊:
  • 影响因子:
  • 作者:
    Martin Daily;Thomas Whale;Peter Kilbride;Stephen Lamb;Benjamin Murray;Helen Picton;John Morris
  • 通讯作者:
    John Morris
A mineral ice-nucleating agent virtually eliminates aqueous supercooling and improves slow-freezing cryopreservation
  • DOI:
    10.1016/j.cryobiol.2024.105001
  • 发表时间:
    2024-12-01
  • 期刊:
  • 影响因子:
  • 作者:
    Martin Daily;Emily Darby;Aimee Bufton;Thomas Whale;Benjamin Murray;Helen Picton
  • 通讯作者:
    Helen Picton
Cryopreservation of bovine granulosa in 96-well plates enhanced by ice nucleation controL
  • DOI:
    10.1016/j.cryobiol.2018.10.245
  • 发表时间:
    2018-12-01
  • 期刊:
  • 影响因子:
  • 作者:
    Martin Daily;Thomas Whale;Helen Picton;George Morris;Peter Kilbride;Stephen Lamb;Benjamin Murray
  • 通讯作者:
    Benjamin Murray

Helen Picton的其他文献

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{{ truncateString('Helen Picton', 18)}}的其他基金

MRC IAA 2021 University of Leeds
MRC IAA 2021 利兹大学
  • 批准号:
    MR/X502789/1
  • 财政年份:
    2022
  • 资助金额:
    $ 166.78万
  • 项目类别:
    Research Grant
The Life Cycle And Legacy of Human Oocytes In Health, Age and Infertility
人类卵母细胞在健康、年龄和不孕症方面的生命周期和遗产
  • 批准号:
    MR/K020501/1
  • 财政年份:
    2013
  • 资助金额:
    $ 166.78万
  • 项目类别:
    Research Grant
Oocyte quality in health and disease
健康和疾病中的卵母细胞质量
  • 批准号:
    G0800250/1
  • 财政年份:
    2008
  • 资助金额:
    $ 166.78万
  • 项目类别:
    Research Grant
Biological foundation for epigenetic investigations of ART derived human oocytes and embryos
ART 衍生的人类卵母细胞和胚胎表观遗传学研究的生物学基础
  • 批准号:
    G0701388/1
  • 财政年份:
    2008
  • 资助金额:
    $ 166.78万
  • 项目类别:
    Research Grant

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